Study to Evaluate Pharmacokinetic Comparability Between AZD7442 Co-formulation (AZD8895 + AZD1061) vs AZD8895 and AZD1061 Individually in Adult Healthy Participants

Study identifier:D8850C00009

ClinicalTrials.gov identifier:NCT05166421

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

Phase 1, Randomized, Open label, Three-arm, Single Dose, Parallel Group Study to Compare AZD7442 (AZD8895 + AZD1061) Pharmacokinetic Exposure Following Intramuscular Administration as a Co-formulation versus Administration from Two Separate Vials of the Individual Monoclonal Antibodies in Adult Healthy Participants

Medical condition

Corona virus disease

Phase

Phase 1

Healthy volunteers

Yes

Study drug

Sex

All

Actual Enrollment

224

Study type

Interventional

Age

18 Years - 79 Years

Date

Study Start Date: 30 Nov 2021

Primary Completion Date: 19 Jul 2023

Study Completion Date: 19 Jul 2023

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Oct 2024 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

- Healthy participants according to medical history, physical examination, and baseline safety laboratory tests.
- Documented negative results of a Severe Acute Respiratory Syndrome Corona Virus 2 reverse transcriptase polymerase chain reaction (SARS-CoV-2 RT-PCR) test collected ≤ 3 days prior to investigational medicinal drug (IMP) dose administration (Day 1) or a negative rapid SARS-CoV-2 antigen test on Day 1 (pre-dose).
- Able to complete the Follow-up period up to Day 361 as required by the protocol.
- Body weight ≥ 50 kg to ≤ 110 kg at screening and a Body mass index ≥ 18.0 to ≤ 30 kg/m^2 at the time of the Screening Visit.

Exclusion Criteria

- Known history of allergy or reaction to any component of AZD7442 (AZD8895 + AZD1061).
- History of infection with SARS or Middle East Respiratory Syndrome.
- Positive SARSCoV-2 result based on available data at screening or at Day 1.
- Any clinical signs and symptoms consistent with Corona virus disease 2019 (COVID-19), eg, fever, dry cough, dyspnea, sore throat, fatigue, or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on admission.
- History of clinically significant bleeding disorder.
- Active infection with hepatitis B or C or positive test for hepatitis C or for hepatitis B surface antigen at screening.
- Immunodeficiency due to illness, including HIV infection, or due to drugs, including any course of glucocorticoid therapy exceeding 2 weeks of prednisone.
- Any other significant disease, disorder, or finding that may significantly increase the risk to the participant because of participation in the study
-Any prior receipt of another mAb indicated for the prevention or treatment of SARS CoV-2 or COVID-19.
- Receipt of a mAb within 6 months or 5 antibody half-lives.
- Receipt of a COVID-19 vaccination ≤ 14 days before IMP administration (Day 1) or plan to receive a COVID-19 vaccination ≤ 14 days after IMP dose (such participants can subsequently be included in the study once they have reached > 14 days after their last dose of vaccine).

Location

Research Site

Houston, TX, United States, 77058

Location

Research Site

La Mesa, CA, United States, 91942

Location

Research Site

Chula Vista, CA, United States, 91911

Location

Research Site

Scottsdale, AZ, United States, 85260

Location

Research Site

Lake Worth, FL, United States, 33462

Location

Research Site

Berlin, NJ, United States, 08009

Location

Research Site

Meridian, ID, United States, 83642

Location

Research Site

North Hollywood, CA, United States, 91606

Arms	Assigned Interventions
Experimental: AZD7442 (co-formulation) Participants will receive single dose of AZD7442 (co-formulation of AZD8895 + AZD1061) on Day 1.	Biological/Vaccine: AZD7442 AZD7442 will be administered via IM route.
Active Comparator: AZD8895 and AZD1061 (clonal cell line material) Participants will receive two separate doses of the individual mAbs (AZD8895 and then AZD1061) on Day 1.	Biological/Vaccine: AZD8895 (clonal cell line material) AZD8895 will be administered via IM route. Biological/Vaccine: AZD1061 (clonal cell line material) AZD1061 will be administered via IM route.
Active Comparator: AZD8895 and AZD1061 (cell pool material) Participants will receive two separate doses of the individual mAbs (AZD8895 and then AZD1061) on Day 1.	Biological/Vaccine: AZD8895 (cell pool material) AZD8895 will be administered via IM route. Biological/Vaccine: AZD1061 (cell pool material) AZD1061 will be administered via IM route.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted between 30-November-2021 (first subject first visit) to 19-July-2023 (last subject last visit).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total 224 participants were randomized in this study. The screening period was up to 28 days. ICF was signed prior to screening procedures. Subjects received study drug in a randomized order. All study assessments were performed as per the schedule of assessments.

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Participant Flow: Overall Study

	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
STARTED	76	72	76
COMPLETED	64	67	62
NOT COMPLETED	12	5	14
Unspecified	3	1	1
Withdrawal by Subject	5	3	6
Lost to Follow-up	4	1	7

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

The safety analysis set included all participants who were randomized and received any amount of investigational medicinal product (IMP).

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Baseline Measures

	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Total
Number of Participants [units: Participants]	76	72	76	224
Sex: Female, Male [units: Participants]
Female	30	33	33	96
Male	46	39	43	128
Age Continuous [units: Years] Mean ± Standard Deviation	42.6 ± 14.1	42.4 ± 15.8	41.0 ± 15.2	42.0 ± 15.0
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0	0	0	0
Asian	2	2	4	8
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	22	19	15	56
White	50	49	54	153
More than one race	0	0	2	2
Unknown or Not Reported	2	2	1	5
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	12	14	13	39
Not Hispanic or Latino	64	58	63	185
Unknown or Not Reported	0	0	0	0

Outcome Measures

1. Primary Outcome Measure: Area Under the Concentration-time Curve from Time Zero Extrapolated to Infinity (AUCinf) [ Time Frame: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361 ]

Measure Type	Primary
Measure Name	Area Under the Concentration-time Curve from Time Zero Extrapolated to Infinity (AUCinf)
Measure Description	The pharmacokinetic (PK [AUCinf]) comparability between AZD7442 administered as a single IM dose (co-formulation) of (AZD8895 + AZD1061) versus two separate IM doses of AZD8895 followed by AZD1061: using clonal cell line material of AZD8895 and AZD1061 was evaluated. The AUCinf comparability between the clonal cell line material and the cell pool material of AZD7442 administered as two separate sequential IM doses of AZD8895 followed by AZD1061 was also evaluated. daymicrograms per milliliter (dayμg/mL)
Time Frame	Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure and 'number analyzed in each row' signifies the participants with available data that were analyzed for each drug for this outcome measure.

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure and 'number analyzed in each row' signifies the participants with available data that were analyzed for each drug for this outcome measure.

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Measured Values

	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Number of Participants Analyzed [units:participants]	63	65	62
Area Under the Concentration-time Curve from Time Zero Extrapolated to Infinity (AUCinf) [units: day*μg/mL] Geometric Mean (Geometric Coefficient of Variation)
AZD7442	4642 (43.12%)	4980 (38.96%)	4666 (41.06%)
AZD8895	2357 (42.72%)	2634 (37.13%)	2405 (41.42%)
AZD1061	2326 (42.69%)	2333 (43.42%)	2255 (41.70%)

Statistical Analysis 1 for Area Under the Concentration-time Curve from Time Zero Extrapolated to Infinity (AUCinf)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)
Other^[5]	0.9380
90% Confidence Interval	( 0.8458 to 1.0403 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUCinf of AZD7442
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Area Under the Concentration-time Curve from Time Zero Extrapolated to Infinity (AUCinf)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	0.9968
90% Confidence Interval	( 0.8980 to 1.1066 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUCinf of AZD7442
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Area Under the Concentration-time Curve from Time Zero Extrapolated to Infinity (AUCinf)

Groups^[1]	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	1.0627
90% Confidence Interval	( 0.9579 to 1.1790 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUCinf of AZD7442
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Area Under the Concentration-time Curve from Time Zero Extrapolated to Infinity (AUCinf)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)
Other^[5]	0.8992
90% Confidence Interval	( 0.8107 to 0.9974 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUCinf of AZD8895
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 5 for Area Under the Concentration-time Curve from Time Zero Extrapolated to Infinity (AUCinf)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	0.9826
90% Confidence Interval	( 0.8854 to 1.0905 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUCinf of AZD8895
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 6 for Area Under the Concentration-time Curve from Time Zero Extrapolated to Infinity (AUCinf)

Groups^[1]	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	1.0928
90% Confidence Interval	( 0.9853 to 1.2120 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUCinf of AZD8895
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 7 for Area Under the Concentration-time Curve from Time Zero Extrapolated to Infinity (AUCinf)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)
Other^[5]	1.0039
90% Confidence Interval	( 0.9029 to 1.1161 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUCinf of AZD1061
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 8 for Area Under the Concentration-time Curve from Time Zero Extrapolated to Infinity (AUCinf)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	1.0336
90% Confidence Interval	( 0.9288 to 1.1503 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUCinf of AZD1061
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 9 for Area Under the Concentration-time Curve from Time Zero Extrapolated to Infinity (AUCinf)

Groups^[1]	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	1.0296
90% Confidence Interval	( 0.9258 to 1.1451 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUCinf of AZD1061
[5]	Other relevant estimation information:
	No text entered.

2. Primary Outcome Measure: Area Under the Serum Concentration-time Curve from Day Zero to the Last Measurable Concentration (AUClast) [ Time Frame: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361 ]

Measure Type	Primary
Measure Name	Area Under the Serum Concentration-time Curve from Day Zero to the Last Measurable Concentration (AUClast)
Measure Description	The PK (AUClast) comparability between AZD7442 administered as a single IM dose (co-formulation) of (AZD8895 + AZD1061) versus two separate IM doses of AZD8895 followed by AZD1061: using clonal cell line material of AZD8895 and AZD1061 was evaluated. The AUClast comparability between the clonal cell line material and the cell pool material of AZD7442 administered as two separate sequential IM doses of AZD8895 followed by AZD1061 was also evaluated.
Time Frame	Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Measured Values

	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Number of Participants Analyzed [units:participants]	65	65	62
Area Under the Serum Concentration-time Curve from Day Zero to the Last Measurable Concentration (AUClast) [units: day*μg/mL] Geometric Mean (Geometric Coefficient of Variation)
AZD7442	4362 (43.55%)	4685 (38.60%)	4406 (40.41%)
AZD8895	2148 (47.37%)	2464 (36.34%)	2254 (40.54%)
AZD1061	2191 (43.70%)	2204 (43.62%)	2145 (41.27%)

Statistical Analysis 1 for Area Under the Serum Concentration-time Curve from Day Zero to the Last Measurable Concentration (AUClast)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)
Other^[5]	0.9418
90% Confidence Interval	( 0.8512 to 1.0421 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUClast of AZD7442
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Area Under the Serum Concentration-time Curve from Day Zero to the Last Measurable Concentration (AUClast)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	0.9973
90% Confidence Interval	( 0.9004 to 1.1046 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUClast of AZD7442
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Area Under the Serum Concentration-time Curve from Day Zero to the Last Measurable Concentration (AUClast)

Groups^[1]	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	1.0589
90% Confidence Interval	( 0.9559 to 1.1730 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUClast of AZD7442
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Area Under the Serum Concentration-time Curve from Day Zero to the Last Measurable Concentration (AUClast)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)
Other^[5]	0.8812
90% Confidence Interval	( 0.7933 to 0.9788 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUClast of AZD8895
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 5 for Area Under the Serum Concentration-time Curve from Day Zero to the Last Measurable Concentration (AUClast)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	0.9600
90% Confidence Interval	( 0.8633 to 1.0674 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUClast of AZD8895
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 6 for Area Under the Serum Concentration-time Curve from Day Zero to the Last Measurable Concentration (AUClast)

Groups^[1]	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	1.0894
90% Confidence Interval	( 0.9796 to 1.2116 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUClast of AZD8895
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 7 for Area Under the Serum Concentration-time Curve from Day Zero to the Last Measurable Concentration (AUClast)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)
Other^[5]	1.0065
90% Confidence Interval	( 0.9061 to 1.1180 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUClast of AZD1061
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 8 for Area Under the Serum Concentration-time Curve from Day Zero to the Last Measurable Concentration (AUClast)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	1.0293
90% Confidence Interval	( 0.9257 to 1.1446 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUClast of AZD1061
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 9 for Area Under the Serum Concentration-time Curve from Day Zero to the Last Measurable Concentration (AUClast)

Groups^[1]	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	1.0227
90% Confidence Interval	( 0.9196 to 1.1373 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of AUClast of AZD1061
[5]	Other relevant estimation information:
	No text entered.

3. Primary Outcome Measure: Maximum Observed Serum (Peak) Concentration (Cmax) [ Time Frame: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361 ]

Measure Type	Primary
Measure Name	Maximum Observed Serum (Peak) Concentration (Cmax)
Measure Description	The PK (Cmax) comparability between AZD7442 administered as a single IM dose (co-formulation) of (AZD8895 + AZD1061) versus two separate IM doses of AZD8895 followed by AZD1061: using clonal cell line material of AZD8895 and AZD1061 was evaluated. The Cmax comparability between the clonal cell line material and the cell pool material of AZD7442 administered as two separate sequential IM doses of AZD8895 followed by AZD1061 was also evaluated.
Time Frame	Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Measured Values

	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Number of Participants Analyzed [units:participants]	71	69	71
Maximum Observed Serum (Peak) Concentration (Cmax) [units: Micrograms per milliliter (μg/mL)] Geometric Mean (Geometric Coefficient of Variation)
AZD7442	37.60 (40.64%)	36.48 (40.28%)	37.76 (33.64%)
AZD8895	18.69 (41.33%)	19.25 (37.01%)	19.37 (33.26%)
AZD1061	18.95 (42.15%)	17.29 (47.17%)	18.53 (36.49%)

Statistical Analysis 1 for Maximum Observed Serum (Peak) Concentration (Cmax)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)
Other^[5]	1.0308
90% Confidence Interval	( 0.9451 to 1.1243 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of Cmax of AZD7442
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Maximum Observed Serum (Peak) Concentration (Cmax)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	0.9930
90% Confidence Interval	( 0.9112 to 1.0822 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of Cmax of AZD7442
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Maximum Observed Serum (Peak) Concentration (Cmax)

Groups^[1]	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	0.9634
90% Confidence Interval	( 0.8833 to 1.0507 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of Cmax of AZD7442
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Maximum Observed Serum (Peak) Concentration (Cmax)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)
Other^[5]	0.9701
90% Confidence Interval	( 0.8894 to 1.0582 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of Cmax of AZD8895
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 5 for Maximum Observed Serum (Peak) Concentration (Cmax)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	0.9629
90% Confidence Interval	( 0.8835 to 1.0494 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of Cmax of AZD8895
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 6 for Maximum Observed Serum (Peak) Concentration (Cmax)

Groups^[1]	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	0.9926
90% Confidence Interval	( 0.9100 to 1.0826 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of Cmax of AZD8895
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 7 for Maximum Observed Serum (Peak) Concentration (Cmax)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)
Other^[5]	1.0976
90% Confidence Interval	( 0.9992 to 1.2057 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of Cmax of AZD1061
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 8 for Maximum Observed Serum (Peak) Concentration (Cmax)

Groups^[1]	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	1.0195
90% Confidence Interval	( 0.9290 to 1.1190 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of Cmax of AZD1061
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 9 for Maximum Observed Serum (Peak) Concentration (Cmax)

Groups^[1]	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material), Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Other^[5]	0.9289
90% Confidence Interval	( 0.8457 to 1.0203 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical Comparison of Cmax of AZD1061
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Time to Maximum Observed Serum Concentration (Tmax) [ Time Frame: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361 ]

Measure Type	Secondary
Measure Name	Time to Maximum Observed Serum Concentration (Tmax)
Measure Description	The PK (Tmax) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs were assessed in healthy adult participants.
Time Frame	Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Measured Values

	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Number of Participants Analyzed [units:participants]	71	69	71
Time to Maximum Observed Serum Concentration (Tmax) [units: Day] Median (Full Range)
AZD7442	13.03 (2.96 to 85.01)	14.00 (2.98 to 90.96)	8.05 (2.97 to 61.95)
AZD8895	13.02 (2.96 to 85.01)	13.98 (2.98 to 90.96)	8.05 (2.97 to 91.07)
AZD1061	13.95 (2.96 to 55.07)	14.00 (1.00 to 63.00)	13.87 (2.98 to 61.95)

No statistical analysis provided for Time to Maximum Observed Serum Concentration (Tmax)

5. Secondary Outcome Measure: Area Under the Serum Concentration-time Curve from Day Zero to 30 days Post-dose (AUC0-31d) [ Time Frame: Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, and 31 ]

Measure Type	Secondary
Measure Name	Area Under the Serum Concentration-time Curve from Day Zero to 30 days Post-dose (AUC0-31d)
Measure Description	The PK (AUC0-31d) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs were assessed in healthy adult participants.
Time Frame	Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, and 31
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Measured Values

	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Number of Participants Analyzed [units:participants]	70	67	68
Area Under the Serum Concentration-time Curve from Day Zero to 30 days Post-dose (AUC0-31d) [units: day*μg/mL] Geometric Mean (Geometric Coefficient of Variation)
AZD7442	903.4 (44.41%)	887.9 (46.19%)	914.2 (40.53%)
AZD8895	447.0 (44.69%)	468.9 (42.98%)	461.7 (41.65%)
AZD1061	453.9 (45.65%)	415.0 (52.77%)	449.3 (42.12%)

No statistical analysis provided for Area Under the Serum Concentration-time Curve from Day Zero to 30 days Post-dose (AUC0-31d)

6. Secondary Outcome Measure: Area Under the Serum Concentration-time Curve from Day Zero to 60 days Post-dose (AUC0-61d) [ Time Frame: Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, 31 and 61 ]

Measure Type	Secondary
Measure Name	Area Under the Serum Concentration-time Curve from Day Zero to 60 days Post-dose (AUC0-61d)
Measure Description	The PK (AUC0-61d) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs were assessed in healthy adult participants.
Time Frame	Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, 31 and 61
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Measured Values

	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Number of Participants Analyzed [units:participants]	69	66	66
Area Under the Serum Concentration-time Curve from Day Zero to 60 days Post-dose (AUC0-61d) [units: day*μg/mL] Geometric Mean (Geometric Coefficient of Variation)
AZD7442	1771 (38.28%)	1752 (38.42%)	1757 (33.67%)
AZD8895	871.4 (39.45%)	918.9 (35.90%)	886.9 (33.87%)
AZD1061	894.6 (39.09%)	826.0 (43.98%)	865.8 (35.33%)

No statistical analysis provided for Area Under the Serum Concentration-time Curve from Day Zero to 60 days Post-dose (AUC0-61d)

7. Secondary Outcome Measure: Area Under the Serum Concentration-time Curve from Day Zero to 90 days Post-dose (AUC0-91d) [ Time Frame: Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, 31, 61 and 91 ]

Measure Type	Secondary
Measure Name	Area Under the Serum Concentration-time Curve from Day Zero to 90 days Post-dose (AUC0-91d)
Measure Description	The PK (AUC0-91d) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs were assessed in healthy adult participants.
Time Frame	Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, 31, 61 and 91
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Measured Values

	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Number of Participants Analyzed [units:participants]	69	66	65
Area Under the Serum Concentration-time Curve from Day Zero to 90 days Post-dose (AUC0-91d) [units: day*μg/mL] Geometric Mean (Geometric Coefficient of Variation)
AZD7442	2444 (37.20%)	2453 (36.03%)	2430 (32.95%)
AZD8895	1201 (38.59%)	1283 (33.67%)	1227 (32.85%)
AZD1061	1236 (37.94%)	1161 (41.27%)	1198 (34.51%)

No statistical analysis provided for Area Under the Serum Concentration-time Curve from Day Zero to 90 days Post-dose (AUC0-91d)

8. Secondary Outcome Measure: Area Under the Serum Concentration-time Curve from Day Zero to 180 days Post-dose (AUC0-181d) [ Time Frame: Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, 31, 61, 91, and 181 ]

Measure Type	Secondary
Measure Name	Area Under the Serum Concentration-time Curve from Day Zero to 180 days Post-dose (AUC0-181d)
Measure Description	The PK (AUC0-181d) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs were assessed in healthy adult participants.
Time Frame	Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, 31, 61, 91, and 181
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Measured Values

	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Number of Participants Analyzed [units:participants]	65	65	63
Area Under the Serum Concentration-time Curve from Day Zero to 180 days Post-dose (AUC0-181d) [units: day*μg/mL] Geometric Mean (Geometric Coefficient of Variation)
AZD7442	3650 (39.01%)	3788 (36.10%)	3655 (36.41%)
AZD8895	1797 (40.54%)	1981 (33.77%)	1856 (36.27%)
AZD1061	1845 (39.46%)	1794 (41.11%)	1793 (37.62%)

No statistical analysis provided for Area Under the Serum Concentration-time Curve from Day Zero to 180 days Post-dose (AUC0-181d)

9. Secondary Outcome Measure: Time of Last Quantifiable Concentration (tlast) [ Time Frame: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 382 ]

Measure Type	Secondary
Measure Name	Time of Last Quantifiable Concentration (tlast)
Measure Description	The PK (tlast) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs were assessed in healthy adult participants.
Time Frame	Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 382
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Measured Values

	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Number of Participants Analyzed [units:participants]	65	65	62
Time of Last Quantifiable Concentration (tlast) [units: Day] Median (Full Range)
AZD7442	357.98 (85.01 to 382.06)	358.02 (60.85 to 367.97)	357.16 (90.98 to 366.23)
AZD8895	357.98 (84.99 to 382.06)	358.02 (60.85 to 367.97)	357.05 (90.98 to 366.23)
AZD1061	357.26 (85.01 to 369.96)	357.98 (60.85 to 367.97)	357.16 (90.98 to 366.23)

No statistical analysis provided for Time of Last Quantifiable Concentration (tlast)

10. Secondary Outcome Measure: Terminal Half-life (t½λz) [ Time Frame: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361 ]

Measure Type	Secondary
Measure Name	Terminal Half-life (t½λz)
Measure Description	The PK (t½λz) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs were assessed in healthy adult participants.
Time Frame	Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
Safety Issue?

Population Description

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Measured Values

	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Number of Participants Analyzed [units:participants]	64	65	62
Terminal Half-life (t½λz) [units: Day] Geometric Mean (Geometric Coefficient of Variation)
AZD7442	75.13 (36.76%)	81.22 (29.11%)	76.52 (32.72%)
AZD8895	77.77 (36.38%)	83.73 (30.12%)	79.19 (33.93%)
AZD1061	74.11 (34.48%)	79.19 (27.68%)	73.71 (31.06%)

No statistical analysis provided for Terminal Half-life (t½λz)

11. Secondary Outcome Measure: Apparent Clearance After Extravascular Administration (CL/F) [ Time Frame: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361 ]

Measure Type	Secondary
Measure Name	Apparent Clearance After Extravascular Administration (CL/F)
Measure Description	The PK (CL/F) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs were assessed in healthy adult participants.
Time Frame	Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
Safety Issue?

Population Description

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Measured Values

	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Number of Participants Analyzed [units:participants]	63	65	62
Apparent Clearance After Extravascular Administration (CL/F) [units: Liter per day (L/day)] Geometric Mean (Geometric Coefficient of Variation)
AZD7442	0.06462 (43.12%)	0.06024 (38.96%)	0.06429 (41.06%)
AZD8895	0.06364 (42.72%)	0.05695 (37.13%)	0.06236 (41.42%)
AZD1061	0.06450 (42.69%)	0.06431 (43.42%)	0.06652 (41.70%)

No statistical analysis provided for Apparent Clearance After Extravascular Administration (CL/F)

12. Secondary Outcome Measure: Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F) [ Time Frame: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361 ]

Measure Type	Secondary
Measure Name	Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F)
Measure Description	The PK (Vz/F) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs were assessed in healthy adult participants.
Time Frame	Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
Safety Issue?

Population Description

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Measured Values

	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Number of Participants Analyzed [units:participants]	63	65	62
Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F) [units: Liter (L)] Geometric Mean (Geometric Coefficient of Variation)
AZD7442	6.960 (35.71%)	7.058 (32.17%)	7.098 (24.94%)
AZD8895	7.129 (35.27%)	6.880 (30.92%)	7.125 (24.29%)
AZD1061	6.852 (36.99%)	7.347 (37.76%)	7.075 (26.48%)

No statistical analysis provided for Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F)

13. Secondary Outcome Measure: Number of Participants with Adverse Events (AEs) [ Time Frame: From Day 1 until Follow-up visit (Day 361) ]

Measure Type	Secondary
Measure Name	Number of Participants with Adverse Events (AEs)
Measure Description	The safety of AZD7442 when administered as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs in healthy adult participants was assessed.
Time Frame	From Day 1 until Follow-up visit (Day 361)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set included all participants who were randomized and received any amount of IMP.

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Measured Values

	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Number of Participants Analyzed [units:participants]	76	72	76
Number of Participants with Adverse Events (AEs) [units: Participants]
Any AE	21	21	26
Any SAE	2	0	1
Any severe AE	1	0	0
Any AESI	1	1	0
Any SAE with outcome death	0	0	0
Any AE leading to study discontinuation	0	0	0
Any possibly related AE	3	1	1
Any possibly related SAE	0	0	0
Any possibly related severe AE	0	0	0
Any possibly related AESI	1	1	0

No statistical analysis provided for Number of Participants with Adverse Events (AEs)

14. Secondary Outcome Measure: Number of Participants with Positive Anti-AZD8895 and anti-AZD1061 Antibodies [ Time Frame: Day 1 (Pre-dose) until Follow-up visit (Day 361) ]

Measure Type	Secondary
Measure Name	Number of Participants with Positive Anti-AZD8895 and anti-AZD1061 Antibodies
Measure Description	The antidrug antibody (ADA) responses to AZD7442 in serum following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs was assessed in healthy adult participants.
Time Frame	Day 1 (Pre-dose) until Follow-up visit (Day 361)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The AZD8895 and AZD1061 ADA Evaluable Analysis Set included participants with at least 1 baseline and 1 post-baseline AZD8895 and AZD1061 ADA measurement. Here, 'number analyzed in each row' signifies the participants with available data that were analyzed for each drug for that outcome measure.

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Measured Values

	Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)
Number of Participants Analyzed [units:participants]	73	70	71
Number of Participants with Positive Anti-AZD8895 and anti-AZD1061 Antibodies [units: Participants]
AZD8895	6	2	2
AZD1061	7	2	1

No statistical analysis provided for Number of Participants with Positive Anti-AZD8895 and anti-AZD1061 Antibodies

Serious Adverse Events

Time Frame	From Day 1 until Follow-up visit (Day 361)
Additional Description	The safety analysis set included all participants who were randomized and received any amount of IMP.

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Serious Adverse Events

Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)

Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)

Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)

Total, serious adverse events

# participants affected / at risk

2/76 (2.63%)

0/72 (0.00%)

1/76 (1.32%)

Psychiatric disorders

Major depression¹,^†

# participants affected / at risk

1/76 (1.32%)

0/72 (0.00%)

0/76 (0.00%)

Cardiac disorders

Angina pectoris¹,^†

# participants affected / at risk

0/76 (0.00%)

0/72 (0.00%)

1/76 (1.32%)

Cardiac disorders

Coronary artery occlusion¹,^†

# participants affected / at risk

1/76 (1.32%)

0/72 (0.00%)

0/76 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 26.0

Other Adverse Events

Time Frame	From Day 1 until Follow-up visit (Day 361)
Additional Description	The safety analysis set included all participants who were randomized and received any amount of IMP.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)	Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)	Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.

Other Adverse Events

Treatment A: AZD8895 and AZD1061 (coformulation, clonal cell line material)

Treatment B: AZD8895 and AZD1061 (separate vials, clonal cell line material)

Treatment C: AZD8895 and AZD1061 (separate vials, cell pool material)

Total, other (not including serious) adverse events

# participants affected / at risk

2/76 (2.63%)

8/72 (11.11%)

10/76 (13.16%)

Infections and infestations

COVID-19¹,^†

# participants affected / at risk

2/76 (2.63%)

8/72 (11.11%)

10/76 (13.16%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 26.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca AB. Access to this document must be restricted to relevant parties.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca Clinical Study Information Center
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

Redacted_CSR_Synopsis
Download
Redacted_CSP
Download
Redacted_SAP
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Redacted_CSR_Synopsis

Redacted_CSP

Redacted_SAP

Trial Results Summaries