A study to assess the pharmacokinetics and safety of single doses of Anifrolumab in healthy subjects

Study identifier:D3461C00006

ClinicalTrials.gov identifier:NCT02601625

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A randomized, phase 1, placebo-controlled, double-blind, single-dose study to evaluate the safety, tolerability and pharmacokinetics of subcutaneously and intravenously delivered Anifrolumab in healthy subjects.

Medical condition

Safety, Healthy subjects

Phase

Phase 1

Healthy volunteers

Yes

Study drug

Anifrolumab SC injection (300mg), Anifrolumab IV infusion (300mg), Anifrolumab SC infusion (600mg), Anifrolumab placebo SC injection (300mg), Anifrolumab placebo IV infusion (300mg), Anifrolumab placebo SC infusion (600mg)

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 55 Years

Date

Study Start Date: 16 Nov 2015

Primary Completion Date: 25 May 2016

Study Completion Date: 25 May 2016

Study design

Allocation: Randomized
Endpoint Classification: Pharmacokinetics
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Basic Science

Verification:

Verified 01 Dec 2022 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1.Provision of signed and dated, written informed consent prior to any study specific procedures.
2.Healthy male and/or female subjects aged 18 – 55 years.
3.Females must have a negative pregnancy test at screening.
4.Females with an intact cervix must have documentation of a Pap smear with no documented malignancy.
5.Have a body mass index (BMI) between 18 and 32 kg/m2, inclusive, and weigh at least 50 kg.
6.Must have adequate abdominal adipose tissue for SC injection.
7.No history of latent or active TB prior to screening.
8.A chest radiograph with no evidence of current active infection or old active TB, malignancy, or clinically significant abnormalities within 6 months prior to screening.

Exclusion Criteria

1.History of any clinically significant disease or disorder which may put the subject at risk .
2.History or presence of hepatic or renal disease.
3.Any clinically significant illness, medical/surgical procedure, or trauma within 8 weeks of participation .
4.Any clinically significant chronic or recent infection requiring hospitalization or treatment with anti-infectives.
5.History of cancer, apart from squamous or basal cell carcinoma of the skin.
6.Any clinically significant lab, vital sign or ECG abnormalities as judged by the investigator.
7.Known history of a primary immunodeficiency,HIV splenectomy or an underlying condition.
8.Any positive result on screening for hepatitis B, hepatitis C or HIV antibody.
9.History of drug abuse within 1 year of participation.
10.Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 4 weeks or 5 half-lives prior to participation.
11.Previous receipt of:
•Anifrolumab;
•B cell-depleting therapy (including but not limited to epratuzumab, ocrelizumab, or rituximab) ≤ 52 weeks prior to screening.
12.History of allergy/hypersensitivity to drugs with a similar chemical structure or class to anifrolumab or to any human gamma globulin therapy.
13.Any live or attenuated vaccine within 8 weeks prior to participation.

Location

Research Site

Baltimore, MD, United States, 21225

Arms	Assigned Interventions
Experimental: Anifrolumab 300 mg SC injections 300 mg single dose anifrolumab delivered as 2 separate 1 mL SC injections administered serially	Drug: Anifrolumab SC injection (300mg) 300 mg of anifrolumab delivered as 2 separate 1 mL SC injections administered serially on Day 1
Experimental: Anifrolumab 300 mg IV infusion 300 mg single dose anifrolumab delivered as an IV infusion over 30 minutes	Drug: Anifrolumab IV infusion (300mg) 300 mg of anifrolumab delivered as an IV infusion over 30 minutes on Day 1
Experimental: Anifrolumab 600 mg SC infusion 600 mg single dose anifrolumab or placebo delivered as 4 mL SC by infusion pump	Drug: Anifrolumab SC infusion (600mg) 600 mg of anifrolumab delivered as 4 mL SC by infusion pump on Day 1
Placebo Comparator: Placebo 300 mg SC injections 300 mg single dose placebo delivered as 2 separate 1 mL SC injections administered serially	Drug: Anifrolumab placebo SC injection (300mg) 300mg of placebo delivered as 2 separate 1 mL SC injections administered serially on Day 1
Placebo Comparator: Placebo 300 mg IV infusion 300 mg single dose placebo delivered as an IV infusion over 30 minutes	Drug: Anifrolumab placebo IV infusion (300mg) 600mg of placebo delivered as an IV infusion over 30 minutes on Day 1
Placebo Comparator: Placebo 600mg SC infusion 600 mg single dose placebo delivered as 4 mL SC by infusion pump	Drug: Anifrolumab placebo SC infusion (600mg) 600 mg of placebo delivered as 4 mL SC by infusion pump on Day 1

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was conducted at the PAREXEL Early Phase Clinical Unit Baltimore, 3001 S. Hanover St. Baltimore, MD 21225 United States of America

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
All eligible participants underwent a screening period of a maximum of 28 days. During the treatment period all participants were asked to be the residents at the study site prior to the evening meal the night before dosing with anifrolumab or placebo (Day -1) until at least 48 hours after dosing; and were then discharged on the morning of Day 3.

Reporting Groups

	Description
Anifrolumab 300 mg SC injections	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Anifrolumab 300 mg IV infusion	Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1
Anifrolumab 600 mg SC infusion	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1
Pooled Placebo	Randomized participants received Anifrolumab matching placebo.

Participant Flow: Overall Study

	Anifrolumab 300 mg SC injections	Anifrolumab 300 mg IV infusion	Anifrolumab 600 mg SC infusion	Pooled Placebo
STARTED	6	6	6	12
COMPLETED	6	6	5	11
NOT COMPLETED	0	0	1	1
Lost to Follow-up	0	0	1	1

Baseline Characteristics

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

Thirty healthy male and female subjects were included in this study, 6 subjects per anifrolumab treatment (300 mg anifrolumab SC, 300 mg anifrolumab IV, 600 mg anifrolumab SC) and 12 subjects for placebo treatment.

Reporting Groups

	Description
Anifrolumab 300 mg SC injections	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Anifrolumab 300 mg IV infusion	Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1
Anifrolumab 600 mg SC infusion	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1
Pooled Placebo	Randomized participants received Anifrolumab matching placebo.

Baseline Measures

	Anifrolumab 300 mg SC injections	Anifrolumab 300 mg IV infusion	Anifrolumab 600 mg SC infusion	Pooled Placebo	Total
Number of Participants [units: Participants]	6	6	6	12	30
Age Continuous [units: Years] Mean ± Standard Deviation	27.5 ± 6.89	29.7 ± 7.97	26.3 ± 6.65	38.4 ± 12.26	32.1 ± 10.62
Sex/Gender, Customized [units: Count of participants]
Female	4	1	2	4	11
Male	2	5	4	8	19

Outcome Measures

1. Primary Outcome Measure: Pharmacokinetics: Observed maximum serum concentration (Cmax) following single dose of anifrolumab. [ Time Frame: On Day 1 pre-dose and at 5 minutes (IV cohort only), 24 and 48 hours post-dose and at each follow-up visit, up to 85 days ]

Measure Type	Primary
Measure Name	Pharmacokinetics: Observed maximum serum concentration (Cmax) following single dose of anifrolumab.
Measure Description	To evaluate Cmax of anifrolumab after single administration of two doses subcutaneously and one dose intravenously. Up to 13 blood samples were collected in total.
Time Frame	On Day 1 pre-dose and at 5 minutes (IV cohort only), 24 and 48 hours post-dose and at each follow-up visit, up to 85 days
Safety Issue?	No

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 pharmacokinetic (PK) analysis set consisted of all participants in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations that had an impact on the analysis of the PK data

Reporting Groups

	Description
Anifrolumab 300 mg SC injections	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Anifrolumab 300 mg IV infusion	Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1
Anifrolumab 600 mg SC infusion	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1

Measured Values

	Anifrolumab 300 mg SC injections	Anifrolumab 300 mg IV infusion	Anifrolumab 600 mg SC infusion
Number of Participants Analyzed [units:participants]	6	6	6
Pharmacokinetics: Observed maximum serum concentration (Cmax) following single dose of anifrolumab. [units: ug/mL] Mean (Standard Deviation)	36.22 (11.63)	82.44 (13.16)	63.86 (20.45)

No statistical analysis provided for Pharmacokinetics: Observed maximum serum concentration (Cmax) following single dose of anifrolumab.

2. Primary Outcome Measure: Pharmacokinetics: Area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t) following single dose of anifrolumab [ Time Frame: On Day 1 pre-dose and at 5 minutes (IV cohort only), 24 and 48 hours post-dose and at each follow-up visit, up to 85 days ]

Measure Type	Primary
Measure Name	Pharmacokinetics: Area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t) following single dose of anifrolumab
Measure Description	To evaluate AUC(0-t) of anifrolumab after single administration of two doses subcutaneously and one dose intravenously Up to 13 blood samples were collected in total.
Time Frame	On Day 1 pre-dose and at 5 minutes (IV cohort only), 24 and 48 hours post-dose and at each follow-up visit, up to 85 days
Safety Issue?	No

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 for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations that had an impact on the analysis of the PK data

Reporting Groups

	Description
Anifrolumab 300 mg SC injections	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Anifrolumab 300 mg IV infusion	Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1
Anifrolumab 600 mg SC infusion	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1

Measured Values

	Anifrolumab 300 mg SC injections	Anifrolumab 300 mg IV infusion	Anifrolumab 600 mg SC infusion
Number of Participants Analyzed [units:participants]	6	6	6
Pharmacokinetics: Area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t) following single dose of anifrolumab [units: day*μg/mL] Mean (Standard Deviation)	769.1 (336.9)	902.9 (175.8)	1639 (557.7)

No statistical analysis provided for Pharmacokinetics: Area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t) following single dose of anifrolumab

3. Primary Outcome Measure: Pharmacokinetics: Area under serum concentration-time curve from time zero extrapolated to infinity (AUC) following single dose of anifrolumab [ Time Frame: On Day 1 pre-dose and at 5 minutes (IV cohort only), 24 and 48 hours post-dose and at each follow-up visit, up to 85 days ]

Measure Type	Primary
Measure Name	Pharmacokinetics: Area under serum concentration-time curve from time zero extrapolated to infinity (AUC) following single dose of anifrolumab
Measure Description	To evaluate AUC of anifrolumab after single administration of two doses subcutaneously and one dose intravenously. Up to 13 blood samples were collected in total.
Time Frame	On Day 1 pre-dose and at 5 minutes (IV cohort only), 24 and 48 hours post-dose and at each follow-up visit, up to 85 days
Safety Issue?	No

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 for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations that had an impact on the analysis of the PK data

Reporting Groups

	Description
Anifrolumab 300 mg SC injections	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Anifrolumab 300 mg IV infusion	Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1
Anifrolumab 600 mg SC infusion	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1

Measured Values

	Anifrolumab 300 mg SC injections	Anifrolumab 300 mg IV infusion	Anifrolumab 600 mg SC infusion
Number of Participants Analyzed [units:participants]	6	6	6
Pharmacokinetics: Area under serum concentration-time curve from time zero extrapolated to infinity (AUC) following single dose of anifrolumab [units: day*μg/mL] Mean (Standard Deviation)	784.6 (330.6)	906.5 (174.9)	1828 (679.8)

No statistical analysis provided for Pharmacokinetics: Area under serum concentration-time curve from time zero extrapolated to infinity (AUC) following single dose of anifrolumab

4. Primary Outcome Measure: Safety: Number of participants with adverse events (AEs) [ Time Frame: From screening to final follow-up visit, up to 16 weeks ]

Measure Type	Primary
Measure Name	Safety: Number of participants with adverse events (AEs)
Measure Description	To assess the safety and tolerability of single doses of anifrolumab
Time Frame	From screening to final follow-up visit, up to 16 weeks
Safety Issue?	Yes

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 received at least 1 dose of investigational medicinal product (IMP) (anifrolumab or placebo) and for whom any safety post-dose data were available.

Reporting Groups

	Description
Anifrolumab 300 mg SC injections	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Anifrolumab 300 mg IV infusion	Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1
Anifrolumab 600 mg SC infusion	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1
Pooled Placebo	Randomized participants received Anifrolumab matching placebo.
Placebo 300 mg Anifrolumab SC	Participants received a single dose of placebo 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Placebo 600 mg Anifrolumab SC	Participants received single dose of placebo 600 mg delivered as 4 mL SC by infusion pump.
Placebo 300 mg Anifrolumab IV	Participants received Single dose of placebo 300 mg delivered as an IV infusion over 30 minutes.
All anifrolumab participants	Overall number of participants who received anifrolumab therapy.

Measured Values

	Anifrolumab 300 mg SC injections	Anifrolumab 300 mg IV infusion	Anifrolumab 600 mg SC infusion	Pooled Placebo	Placebo 300 mg Anifrolumab SC	Placebo 600 mg Anifrolumab SC	Placebo 300 mg Anifrolumab IV	All anifrolumab participants
Number of Participants Analyzed [units:participants]	6	6	6	12	4	4	4	18
Safety: Number of participants with adverse events (AEs) [units: Participants]	3	2	4	4	1	2	1	9

No statistical analysis provided for Safety: Number of participants with adverse events (AEs)

5. Primary Outcome Measure: Safety: Summary of local injection site pain (SC cohorts) assessed in participants [ Time Frame: Immediately after dosing, at 10, 20 minutes and 1 hour after injection ]

Measure Type	Primary
Measure Name	Safety: Summary of local injection site pain (SC cohorts) assessed in participants
Measure Description	Local injection site pain was assessed using a 100 mm participant rated Visual Analog Scale (VAS 0mm – 100mm ungraduated scale, where 0 = “no pain” to 100 = “worst imaginable pain”). This assessment was taken for only those participants in subcutaneously dosed treatment groups; 600 mg SC and 300 mg SC, anifrolumab and placebo. For the 300 mg SC anifrolumab and 300 mg SC placebo groups which received two simultaneous injections, the average VAS score (0mm-100mm) of the two injection sites were reported.
Time Frame	Immediately after dosing, at 10, 20 minutes and 1 hour after injection
Safety Issue?	Yes

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 received at least 1 dose of IMP (anifrolumab or placebo) and for whom any safety post-dose data were available.

Reporting Groups

	Description
Anifrolumab 300 mg SC injections	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Anifrolumab 600 mg SC infusion	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1
Placebo 300 mg Anifrolumab SC	Participants received a single dose of placebo 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Placebo 600 mg Anifrolumab SC	Participants received single dose of placebo 600 mg delivered as 4 mL SC by infusion pump.

Measured Values

	Anifrolumab 300 mg SC injections	Anifrolumab 600 mg SC infusion	Placebo 300 mg Anifrolumab SC	Placebo 600 mg Anifrolumab SC
Number of Participants Analyzed [units:participants]	6	6	4	4
Safety: Summary of local injection site pain (SC cohorts) assessed in participants [units: Millimeter] Mean (Standard Deviation)
Immediately after dosing	1.2 (2.21)	0.0 (0.00)	8.0 (13.69)	0.0 (0.00)
10 min after injection	0.5 (0.63)	0.0 (0.00)	0.5 (1.00)	0.0 (0.00)
20 min after injection	0.3 (0.42)	0.0 (0.00)	0.4 (0.75)	0.3 (0.50)
1 hour after injection	0.2 (0.41)	0.0 (0.00)	0.3 (0.50)	0.0 (0.00)

No statistical analysis provided for Safety: Summary of local injection site pain (SC cohorts) assessed in participants

6. Primary Outcome Measure: Safety: Summary of local injection site pruritus (SC cohorts) assessed in participants [ Time Frame: Immediately after dosing, at 10, 20 minutes and 1 hour after injection ]

Measure Type	Primary
Measure Name	Safety: Summary of local injection site pruritus (SC cohorts) assessed in participants
Measure Description	Local injection site pruritus was assessed using a 100 mm participant rated Visual Analog Scale (VAS 0mm – 100mm ungraduated scale, where 0 = “no itching” to 100 = “worst imaginable itching”). This assessment was taken for only those participants in subcutaneously dosed treatment groups; 600 mg SC and 300 mg SC, anifrolumab and placebo. For the 300 mg SC anifrolumab and 300 mg SC placebo groups which received two simultaneous injections, the average VAS score (0mm-100mm) of the two injection sites were reported.
Time Frame	Immediately after dosing, at 10, 20 minutes and 1 hour after injection
Safety Issue?	Yes

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 received at least 1 dose of IMP (anifrolumab or placebo) and for whom any safety post-dose data were available.

Reporting Groups

	Description
Anifrolumab 300 mg SC injections	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Anifrolumab 600 mg SC infusion	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1
Placebo 300 mg Anifrolumab SC	Participants received a single dose of placebo 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Placebo 600 mg Anifrolumab SC	Participants received single dose of placebo 600 mg delivered as 4 mL SC by infusion pump.

Measured Values

	Anifrolumab 300 mg SC injections	Anifrolumab 600 mg SC infusion	Placebo 300 mg Anifrolumab SC	Placebo 600 mg Anifrolumab SC
Number of Participants Analyzed [units:participants]	6	6	4	4
Safety: Summary of local injection site pruritus (SC cohorts) assessed in participants [units: Millimeter] Mean (Standard Deviation)
Immediately after dosing	1.3 (2.60)	14.0 (20.29)	1.3 (1.66)	0.8 (0.96)
10 min after injection	0.7 (1.21)	6.3 (14.56)	0.6 (1.25)	0.0 (0.00)
20 min after injection	0.3 (0.52)	1.5 (3.67)	0.5 (1.00)	0.3 (0.50)
1 hour after injection	0.1 (0.20)	0.0 (0.00)	0.4 (0.75)	0.0 (0.00)

No statistical analysis provided for Safety: Summary of local injection site pruritus (SC cohorts) assessed in participants

7. Primary Outcome Measure: Safety: Summary of erythema injection site reaction (SC cohorts) assessed in participants [ Time Frame: Immediately after dosing, at 10, 20 minutes and 1 hour after injection ]

Measure Type	Primary
Measure Name	Safety: Summary of erythema injection site reaction (SC cohorts) assessed in participants
Measure Description	Erythema was measured as the largest diameter across the needle site on the skin in millimetres (mm). This assessment was taken for only those participants in subcutaneously dosed treatment groups; 600 mg SC and 300 mg SC, anifrolumab and placebo. For the 300 mg SC anifrolumab and 300 mg SC placebo groups which received two simultaneous injections, the average of the two injection site diameters (mm) were reported.
Time Frame	Immediately after dosing, at 10, 20 minutes and 1 hour after injection
Safety Issue?	Yes

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 received at least 1 dose of IMP (anifrolumab or placebo) and for whom any safety post-dose data were available.

Reporting Groups

	Description
Anifrolumab 300 mg SC injections	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Anifrolumab 600 mg SC infusion	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1
Placebo 300mg SC injection	Participants received 300 mg single dose placebo delivered as 2 separate 1 mL SC injections administered serially on Day 1.
Placebo 600 mg SC injection	Participants received placebo 600mg

Measured Values

	Anifrolumab 300 mg SC injections	Anifrolumab 600 mg SC infusion	Placebo 300mg SC injection	Placebo 600 mg SC injection
Number of Participants Analyzed [units:participants]	6	6	4	4
Safety: Summary of erythema injection site reaction (SC cohorts) assessed in participants [units: Millimeter] Mean (Standard Deviation)
Immediately after dosing	0.3 (0.42)	17.0 (19.75)	11.5 (14.62)	20.0 (13.54)
10 minutes after injection	2.0 (4.18)	17.5 (21.39)	5.1 (9.59)	18.0 (14.99)
20 minute after injection	2.7 (4.14)	16.6 (20.81)	5.5 (9.11)	26.0 (18.55)
1 hour after injection	0.3 (0.52)	2.5 (6.12)	0.3 (0.50)	10.0 (14.14)

No statistical analysis provided for Safety: Summary of erythema injection site reaction (SC cohorts) assessed in participants

8. Primary Outcome Measure: Safety: Summary of the induration injection site reaction (SC cohorts) assessed in participants [ Time Frame: Immediately after dosing, at 10, 20 minutes and 1 hour after injection ]

Measure Type	Primary
Measure Name	Safety: Summary of the induration injection site reaction (SC cohorts) assessed in participants
Measure Description	Induration was measured as the largest diameter across the needle site on the skin in millimetres (mm). This assessment was taken for only those participants in subcutaneously dosed treatment groups; 600 mg SC and 300 mg SC, anifrolumab and placebo. For the 300 mg SC anifrolumab and 300 mg SC placebo groups which received two simultaneous injections, the average of the two injection site diameters (mm) were reported.
Time Frame	Immediately after dosing, at 10, 20 minutes and 1 hour after injection
Safety Issue?	Yes

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 received at least 1 dose of IMP (anifrolumab or placebo) and for whom any safety post-dose data were available.

Reporting Groups

	Description
Anifrolumab 300 mg SC injections	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Anifrolumab 600 mg SC infusion	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1
Placebo 300mg SC injection	Participants received 300 mg single dose placebo delivered as 2 separate 1 mL SC injections administered serially on Day 1.
Placebo 600 mg Anifrolumab SC	Participants received single dose of placebo 600 mg delivered as 4 mL SC by infusion pump.

Measured Values

	Anifrolumab 300 mg SC injections	Anifrolumab 600 mg SC infusion	Placebo 300mg SC injection	Placebo 600 mg Anifrolumab SC
Number of Participants Analyzed [units:participants]	6	6	4	4
Safety: Summary of the induration injection site reaction (SC cohorts) assessed in participants [units: Millimeter] Mean (Standard Deviation)
Immediately after dosing	4.2 (10.21)	22.5 (13.69)	0.0 (0.00)	12.5 (15.00)
10 minutes after injection	0.8 (2.04)	17.3 (12.39)	0.0 (0.00)	16.5 (19.21)
20 minute after injection	0.1 (0.20)	14.1 (11.41)	0.1 (0.25)	8.0 (16.00)
1 hour after injection	0.0 (0.00)	11.7 (13.29)	0.0 (0.00)	12.5 (25.00)

No statistical analysis provided for Safety: Summary of the induration injection site reaction (SC cohorts) assessed in participants

9. Secondary Outcome Measure: Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the measurement of Anti-drug Antibody (ADA). [ Time Frame: Pre-dose and at Days 5 and Day 29, up to 85 days ]

Measure Type	Secondary
Measure Name	Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the measurement of Anti-drug Antibody (ADA).
Measure Description	Immunogenicity was assessed in all groups by the presence or absence of ADA, which was determined in serum samples using validated bioanalytical methods. The reported results are based on the confirmatory assay (positive/negative) of the ADA. The number of participants with positive, negative and missing results are reported for each time point using the safety analysis set.
Time Frame	Pre-dose and at Days 5 and Day 29, up to 85 days
Safety Issue?	No

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 subjects who received at least 1 dose of IMP (anifrolumab or placebo) and for whom any safety post-dose data were available.

Reporting Groups

	Description
Anifrolumab 300 mg SC injections	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Anifrolumab 300 mg IV infusion	Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1
Anifrolumab 600 mg SC infusion	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1
Pooled Placebo	Randomized participants received Anifrolumab matching placebo.
All subjects	Overall participants.

Measured Values

	Anifrolumab 300 mg SC injections	Anifrolumab 300 mg IV infusion	Anifrolumab 600 mg SC infusion	Pooled Placebo	All subjects
Number of Participants Analyzed [units:participants]	6	6	6	12	30
Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the measurement of Anti-drug Antibody (ADA). [units: Participants]
Day 1, pre-dose (positive)	0	0	0	0	0
Day 1, pre-dose (negative)	6	6	6	12	30
Day 1, pre-dose (missing)	0	0	0	0	0
Day 5 (positive)	0	0	0	0	0
Day 5 (negative)	6	6	6	12	30
Day 5 (missing)	0	0	0	0	0
Day 29 (positive)	0	0	0	0	0
Day 29 (negative)	6	6	5	11	28
Day 29 (missing)	0	0	1	1	2
Day 85 (positive)	0	1	0	0	1
Day 85 (negative)	6	5	5	11	27
Day 85 (missing)	0	0	1	1	2

No statistical analysis provided for Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the measurement of Anti-drug Antibody (ADA).

Serious Adverse Events

Time Frame	From screening to final follow-up visit, up to 16 weeks
Additional Description	An adverse event (AE) is any undesirable medical condition or the deterioration of a pre existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.

Reporting Groups

	Description
Anifrolumab 300 mg SC injections	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Anifrolumab 300 mg IV infusion	Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1
Placebo 300 mg Anifrolumab SC	Participants received a single dose of placebo 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Placebo 300 mg IV infusion	Participants received 300 mg single dose placebo delivered as an IV infusion over 30 minutes on Day 1.
Placebo 600 mg Anifrolumab (SC)	Participants received 600 mg single dose placebo delivered as 4 mL SC by infusion pump on Day 1.
Anifrolumab 600 mg SC infusion	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1
Pooled Placebo	Randomized participants received Anifrolumab matching placebo.
All anifrolumab subjects	Overall number of participants who received anifrolumab therapy

Serious Adverse Events

	Anifrolumab 300 mg SC injections	Anifrolumab 300 mg IV infusion	Placebo 300 mg Anifrolumab SC	Placebo 300 mg IV infusion	Placebo 600 mg Anifrolumab (SC)	Anifrolumab 600 mg SC infusion	Pooled Placebo	All anifrolumab subjects
Total, serious adverse events
# participants affected / at risk	0/6 (0.00%)	0/6 (0.00%)	0/4 (0.00%)	0/4 (0.00%)	0/4 (0.00%)	0/6 (0.00%)	0/12 (0.00%)	0/18 (0.00%)

Other Adverse Events

Time Frame	From screening to final follow-up visit, up to 16 weeks
Additional Description	An adverse event (AE) is any undesirable medical condition or the deterioration of a pre existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Anifrolumab 300 mg SC injections	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Anifrolumab 300 mg IV infusion	Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1
Placebo 300 mg Anifrolumab SC	Participants received a single dose of placebo 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.
Placebo 300 mg IV infusion	Participants received 300 mg single dose placebo delivered as an IV infusion over 30 minutes on Day 1.
Placebo 600 mg Anifrolumab (SC)	Participants received 600 mg single dose placebo delivered as 4 mL SC by infusion pump on Day 1.
Anifrolumab 600 mg SC infusion	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1
Pooled Placebo	Randomized participants received Anifrolumab matching placebo.
All anifrolumab subjects	Overall number of participants who received anifrolumab therapy

Other Adverse Events

Anifrolumab 300 mg SC injections

Anifrolumab 300 mg IV infusion

Placebo 300 mg Anifrolumab SC

Placebo 300 mg IV infusion

Placebo 600 mg Anifrolumab (SC)

Anifrolumab 600 mg SC infusion

Pooled Placebo

All anifrolumab subjects

Total, other (not including serious) adverse events

# participants affected / at risk

3/6 (50.00%)

2/6 (33.33%)

1/4 (25.00%)

2/4 (50.00%)

4/6 (66.67%)

4/12 (33.33%)

9/18 (50.00%)

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

2/6 (33.33%)

1/6 (16.67%)

0/4 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

3/18 (16.67%)

Infections and infestations

Tooth abscess¹,^†

# participants affected / at risk

0/6 (0.00%)

0/4 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

1/18 (5.56%)

Infections and infestations

Oral herpes¹,^†

# participants affected / at risk

0/6 (0.00%)

0/4 (0.00%)

1/4 (25.00%)

0/4 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/18 (0.00%)

Infections and infestations

Tinea pedis¹,^†

# participants affected / at risk

0/6 (0.00%)

0/4 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

1/18 (5.56%)

Gastrointestinal disorders

Abdominal discomfort¹,^†

# participants affected / at risk

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/18 (5.56%)

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

0/4 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/18 (5.56%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/18 (5.56%)

General disorders

Chest discomfort¹,^†

# participants affected / at risk

0/6 (0.00%)

0/4 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

1/18 (5.56%)

General disorders

Infusion site pruritus¹,^†

# participants affected / at risk

0/6 (0.00%)

0/4 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

1/18 (5.56%)

General disorders

Peripheral swelling¹,^†

# participants affected / at risk

0/6 (0.00%)

1/4 (25.00%)

0/4 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/18 (0.00%)

General disorders

Vessel puncture site bruise¹,^†

# participants affected / at risk

0/6 (0.00%)

0/4 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

1/18 (5.56%)

Respiratory, thoracic and mediastinal disorders

Dry throat¹,^†

# participants affected / at risk

0/6 (0.00%)

2/6 (33.33%)

0/4 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

2/18 (11.11%)

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

0/4 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/18 (5.56%)

Respiratory, thoracic and mediastinal disorders

Dysphonia¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

0/4 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/18 (5.56%)

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain¹,^†

# participants affected / at risk

0/6 (0.00%)

0/4 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

1/18 (5.56%)

Immune system disorders

Food allergy¹,^†

# participants affected / at risk

0/6 (0.00%)

0/4 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

1/18 (5.56%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

1/4 (25.00%)

0/6 (0.00%)

1/12 (8.33%)

1/18 (5.56%)

Nervous system disorders

Somnolence¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

0/4 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/18 (5.56%)

Reproductive system and breast disorders

Menstrual disorder¹,^†

# participants affected / at risk

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/18 (5.56%)

Skin and subcutaneous tissue disorders

Dermatitis contact¹,^†

# participants affected / at risk

0/6 (0.00%)

0/4 (0.00%)

1/4 (25.00%)

0/6 (0.00%)

1/12 (8.33%)

0/18 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA Version 18.1

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: All of the study information and data collected during the study are confidential and the property of AstraZeneca. After completion of the study, the investigator may prepare a joint publication with AstraZeneca. The investigator must undertake not to submit any part of the individual data from this study for publication without prior consent of AstraZeneca at a mutually agreed time.

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
None

Results Point of Contact

Name/Title:	Anifrolumab Global Clinical Leader
Organization:	AstraZeneca AB
Phone	+46317761000
E-mail:	[email protected]

Documents available

d3461c00006-revised-study-protocol-1_REDACTED
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Ronald Goldwater

PAREXEL Early Phase Clinical Unit, Baltimore, United States of America

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

d3461c00006-revised-study-protocol-1_REDACTED

Trial Results Summaries