Safety and Efficacy of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects with Active Proliferative Lupus Nephritis - TULIP-LN1

Study identifier:D3461C00007

ClinicalTrials.gov identifier:NCT02547922

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Multicentre, Randomised, Double-blind, Placebo-controlled, Phase 2 Study Evaluating the Efficacy and Safety of Anifrolumab in Adult Subjects with Active Proliferative Lupus Nephritis

Medical condition

Lupus Nephritis

Phase

Phase 2

Healthy volunteers

Study drug

Placebo

Sex

All

Actual Enrollment

147

Study type

Interventional

Age

18 Years - 70 Years

Date

Study Start Date: 04 Nov 2015

Primary Completion Date: 26 Nov 2019

Study Completion Date: 18 Jan 2021

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Oct 2021 by AstraZeneca

Collaborators

PAREXEL

Inclusion and exclusion criteria

Inclusion Criteria

1. Age 18 through 70 years at the time of screening
2. Fulfils at least 4 of the 11 criteria of the revised 1982 ACR classification criteria for SLE, at least one of which must be:
a. Positive antinuclear antibody (ANA) test (1:40 or higher) or
b. Elevated anti-dsDNA antibodies at screening (reported as equivocal or positive results), as per the centrallaboratory; or
c. Anti-Smith antibody at screening elevated to above normal (ie, positive or equivocal results) as per the central laboratory
3. Class III (±Class V) or Class IV (±Class V) LN according to the World Health Organisation (WHO) or 2003 ISN/RPS classification based on a renal biopsy obtained within 12 weeks prior to signing the ICF or during the screening period:
4. Urine protein to creatinine ratio >1 gm/gm (113.17 mg/mmol), obtained on a 24-hour urine collection at screening
5. Estimated glomerular filtration rate ≥35 mL/min/1.73 m2
6. Must not have active or latent TB on either chest radiograph or by Quantiferon gold test
7. Women of childbearing potential must have a negative serum beta-hCG test at screening and negative urine pregnancy test prior to the first dose of
sponsor-provided MMF.
Main

Exclusion Criteria

1. Receipt of any investigational product (small molecule or biologic) or commercially available biologic agent within four weeks or 5 half lives prior to signing of the ICF, whichever is greater
2. Pure Class V membranous LN on a renal biopsy obtained within 12 weeks prior to signing ICF or during the screening period
3. Known intolerance to ≤1.0 gm/day of MMF
4. History of dialysis within 12 months prior to signing the ICF or expected need for renal replacement therapy (dialysis or renal transplant) within a 6 month period after enrolment
5. Subjects, who at the time of signing the ICF, received any of the following immunosuppressive therapies after their qualifying biopsy
(a) Oral corticosteroids >0.5 mg/kg/day for more than 8 weeks or
(b) Oral or IV pulse methylprednisolone >3.0 gm (cumulative dose) or
(c) IV cyclophosphamide >2 pulses of high-dose (≥0.5 gm/m2) or >4 doses of low dose (500 mg every 2 weeks) or
(d) Average MMF >2.5 gm/day (>1800 mg/day of enteric-coated mycophenolate sodium) for more than 8 weeks or
(e) Tacrolimus >4 mg/day for more than 8 weeks
6. Major surgery within 8 weeks before signing the ICF or major surgery planned during the study period
7. History of any non-SLE disease that has required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to signing the ICF
8. Confirmed positive test for hepatitis B or hepatitis C
9. Any severe herpes infection at any time prior to randomization
10.Opportunistic infection requiring hospitalisation or parenteral antimicrobial treatment within 3 years prior to randomization (vaginal, oral and skin candidiasis is not an exclusionreason).
11. History of cancer, apart from:
a. Squamous or basal cell carcinoma of the skin that has been successfully treated
b. Cervical cancer in situ that has been successfully treated
12. Concurrent enrolment in another clinical study with an IP within 4 weeks prior to ICF signing or within 5 half-lives of the IP used in that clinical study, whichever is
longer.
13. During screening (within 30 days before Day 1 [Week 0 visit]), any of the following:
(a) Aspartate transaminase (AST) >2.5×upper limit of normal (ULN)
(b) Alanine transaminase (ALT) >2.5×ULN
(c) Total bilirubin >ULN (unless due to Gilbert's syndrome [based on Investigator’s judgement])
(d) Glycosylated haemoglobin (HbA1c) >8% (or >0.08) at screening (diabetic subjects only)
(e) Neutrophil count <1x103/μL (or <1.0 GI/L)
(f) Platelet count <25x103/μL (or <25 GI/L)
(g) Haemoglobin <8 g/dL (or <80 g/L).

Location

Research Site

Debary, FL, United States, 32713

Location

Research Site

Phoenix, AZ, United States, 85032

Location

Research Site

Memphis, TN, United States, 38119

Location

Research Site

La Jolla, CA, United States, 92037-0706

Location

Research Site

Columbus, OH, United States, 43210

Location

Research Site

New York, NY, United States, 10016

Location

Research Site

Glendale, AZ, United States, 85306

Location

Research Site

Bronx, NY, United States, 10457

Arms	Assigned Interventions
Experimental: Anifrolumab - Lower Dose Anifrolumab - Lower Dose	Biological/Vaccine: Anifrolumab Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112
Experimental: Anifrolumab - Higher Dose Anifrolumab - Higher Dose	Biological/Vaccine: Anifrolumab Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112
Placebo Comparator: Placebo Placebo IV Q4W plus SOC	Drug: Placebo Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects who met all the inclusion and none of the exclusion criteria were randomized at 66 sites in 16 countries. The study was conducted from 04 November 2015 to 18 January 2021.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The screening period was from Day -30 to Day -1. Informed consent form (ICF) was signed prior to screening procedures. All the study assessments were performed as per the schedule of assessment.

Reporting Groups

	Description
Anifrolumab - Basic Regimen	Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Anifrolumab - Intensified Regimen	Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Placebo	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.

Participant Flow: Overall Study

	Anifrolumab - Basic Regimen	Anifrolumab - Intensified Regimen	Placebo
STARTED	46	52	49
FAS (Full analysis set)	45	51	49
COMPLETED	18	28	20
NOT COMPLETED	28	24	29
Withdrawal by Subject	9	6	10
Adverse Event	3	1	2
Lost to Follow-up	1	0	0
Lack of Efficacy	5	7	4
Death	1	0	0
Non-responding completer, Not eligible for extension study, Use of any restricted Medications	4	8	9
TECHNICAL PROBLEMS	1	0	0
PROGRESSIVE DISEASE	1	0	2
Physician Decision	2	1	2
Patients did not receive IP	1	1	0

Baseline Characteristics

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

The full analysis set included all subjects who received at least one dose of study treatment and were analyzed according to randomized treatment.

Reporting Groups

	Description
Anifrolumab - Basic Regimen	Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Anifrolumab - Intensified Regimen	Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Placebo	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.

Baseline Measures

	Anifrolumab - Basic Regimen	Anifrolumab - Intensified Regimen	Placebo	Total
Number of Participants [units: Participants]	45	51	49	145
Age Continuous [units: years] Mean ± Standard Deviation	35.2 ± 11.49	35.0 ± 10.58	34.0 ± 10.18	34.7 ± 10.68
Sex: Female, Male [units: ]
Female	37	45	38	120
Male	8	6	11	25
Ethnicity (NIH/OMB) [units: ]
Hispanic or Latino	22	23	20	65
Not Hispanic or Latino	23	28	29	80
Unknown or Not Reported	0	0	0	0
Race/Ethnicity, Customized [units: ]
American Indian or Alaska Native	3	1	0	4
Asian	11	7	10	28
Native Hawaiian or Other Pacific Islander	1	0	0	1
Black or African American	2	4	1	7
White	17	25	24	66
Other	11	14	14	39

Outcome Measures

1. Primary Outcome Measure: Change from baseline in 24-hour urine protein to creatinine ratio (UPCR) [ Time Frame: From Week 1 (Baseline) up to Week 52 ]

Measure Type	Primary
Measure Name	Change from baseline in 24-hour urine protein to creatinine ratio (UPCR)
Measure Description	To evaluate the efficacy of anifrolumab plus SOC (combination of mycophenolate mofetil and corticosteroids) compared with placebo plus SOC in subjects with active proliferative lupus nephritis (LN). Geometric mean ratio of 24-hour UPCR at week 52 over baseline. Values <1 indicate improvement from baseline.
Time Frame	From Week 1 (Baseline) up to Week 52
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.
Full analysis set (FAS): The FAS included all subjects who received at least one dose of study treatment and were analyzed according to randomized treatment (mITT principle). Here, overall number of subjects analyzed signifies the subjects with available data that were analyzed for the outcome measure.

Reporting Groups

	Description
Anifrolumab - Basic Regimen	Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Anifrolumab - Intensified Regimen	Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
All Anifrolumab	This arm comprises Anifrolumab - Basic Regimen and Anifrolumab - Intensified Regimen. Anifrolumab - Basic Regimen: Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112. Anifrolumab - Intensified Regimen: Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Placebo	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.

Measured Values

	Anifrolumab - Basic Regimen	Anifrolumab - Intensified Regimen	All Anifrolumab	Placebo
Number of Participants Analyzed [units:participants]	41	50	91	41
Change from baseline in 24-hour urine protein to creatinine ratio (UPCR) [units: milligram/milligram (mg/mg)] Geometric Mean (95% Confidence Interval)	0.326 (0.190 to 0.561)	0.285 (0.177 to 0.457)	0.305 (0.198 to 0.468)	0.296 (0.175 to 0.499)

Statistical Analysis 1 for Change from baseline in 24-hour urine protein to creatinine ratio (UPCR)

Groups^[1]	All Anifrolumab, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.9052
Other^[5]	1.031
95% Confidence Interval	( 0.621 to 1.713 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The model includes fixed effects for treatment group, visit, stratification factors, log-transformed 24-hour UPCR at baseline, and treatment-by-visit interaction. All data up to and including the date of discontinuation of study treatment were included in the analysis.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	The p-values presented are unadjusted and was compared with the respective adjusted significance level (α). If α is not displayed, no formal testing can be performed and the corresponding p-value was nominal.
[5]	Other relevant estimation information:
	Geometric mean ratio >1 favours placebo.

2. Secondary Outcome Measure: Proportion of subjects achieving the composite endpoint Complete Renal Response (CRR) [ Time Frame: Week 52 ]

Measure Type	Secondary
Measure Name	Proportion of subjects achieving the composite endpoint Complete Renal Response (CRR)
Measure Description	CRR was defined as meeting all of the following: -Estimated glomerular filtration rate (eGFR) is ≥60 mL/min/1.73 m^2 or no confirmed decrease of eGFR from baseline of ≥20% -24-hour UPCR ≤ 0.7 mg/mg -No discontinuation of investigational product (IP) or use of restricted medication beyond the protocol allowed threshold before assessment -eGFR was based on Modification of Diet in Renal Disease (MDRD) formula. Subjects treated with restricted medication beyond the protocol allowed threshold, or discontinuing study treatment for other reasons, were regarded as non-responders.
Time Frame	Week 52
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 FAS included all subjects who received at least one dose of study treatment and were analyzed according to randomized treatment (mITT principle). The subjects being analyzed was less than the number of patients in the FAS. Subjects from France and Italy were excluded from the analysis (France EC and Italy HA did not accept CSP amendment 3 (version 4.0)).

Reporting Groups

	Description
Anifrolumab - Basic Regimen	Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Anifrolumab - Intensified Regimen	Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
All Anifrolumab	This arm comprises Anifrolumab - Basic Regimen and Anifrolumab - Intensified Regimen. Anifrolumab - Basic Regimen: Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112. Anifrolumab - Intensified Regimen: Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Placebo	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.

Measured Values

	Anifrolumab - Basic Regimen	Anifrolumab - Intensified Regimen	All Anifrolumab	Placebo
Number of Participants Analyzed [units:participants]	45	51	96	49
Proportion of subjects achieving the composite endpoint Complete Renal Response (CRR) [units: Percentage of subjects]
Responder	16.3	45.5	31.0	31.1
Non-responder	83.7	54.5	69.0	68.9

Statistical Analysis 1 for Proportion of subjects achieving the composite endpoint Complete Renal Response (CRR)

Groups^[1]	All Anifrolumab, Placebo
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	0.9929
Other^[5]	-0.08
95% Confidence Interval	( -16.92 to 16.76 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The statistical analysis represents the estimated percentage of responders. The responder/non-responder rates (percentages), the difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	At Week 52, the p-values presented are unadjusted and will be compared to the respective adjusted significance level (α). If α is not displayed no formal testing can be performed and the corresponding p-value is nominal.
[5]	Other relevant estimation information:
	No text entered.

3. Other Pre-specified Outcome Measure: Number of subjects with adverse events [ Time Frame: From screening (Day-30 to -1) period until the follow-up period (Week 112) ]

Measure Type	Other Pre-specified
Measure Name	Number of subjects with adverse events
Measure Description	To assess AEs (non-serious, serious and adverse event of special interest (AESI)) as variables of safety and tolerability of anifrolimab. The AESIs are serious infections, including non-opportunistic serious infections, opportunistic infections, anaphylaxis, malignancy, herpes zoster, TB (including latent TB), influenza, vasculitis (non-SLE), and MACE (including stroke, acute coronary syndrome, myocardial infarction, or cardiovascular death). Study period: During treatment and follow-up data are presented.
Time Frame	From screening (Day-30 to -1) period until the follow-up period (Week 112)
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.
Full analysis set (FAS): The FAS included all subjects who received at least one dose of study treatment and were analyzed according to randomized treatment (mITT principle).

Reporting Groups

	Description
Anifrolumab - Basic Regimen	Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Anifrolumab - Intensified Regimen	Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
All Anifrolumab	This arm comprises Anifrolumab - Basic Regimen and Anifrolumab - Intensified Regimen. Anifrolumab - Basic Regimen: Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112. Anifrolumab - Intensified Regimen: Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Placebo	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.

Measured Values

	Anifrolumab - Basic Regimen	Anifrolumab - Intensified Regimen	All Anifrolumab	Placebo
Number of Participants Analyzed [units:participants]	45	51	96	49
Number of subjects with adverse events [units: Participants]
Subjects with any AE- During treatment	43	47	90	44
Subjects with any acute AE- During treatment	11	15	26	14
Any AE with outcome of death- During treatment	0	0	0	0
Any SAE (including events with- outcome of death)- During treatment	10	9	19	8
Any AE leading to discontinuation of investigational product- During treatment	5	6	11	5
Any AE related to investigational product (investigator assessment)- During treatment	24	13	37	16
Any AE of severe intensity- During treatment	6	7	13	8
Any AESI- During treatment	12	12	24	8
Non-opportunistic serious infections- During treatment	0	1	1	3
Opportunistic infections- During treatment	1	0	1	1
Anaphylaxis- During treatment	0	0	0	0
Malignancy- During treatment	0	1	1	0
Herpes zoster- During treatment	9	7	16	4
Tuberculosis/LTB (latent tuberculosis)- During treatment	0	0	0	0
Influenza- During treatment	2	4	6	1
Vasculitis (non-systemic lupus erythematosus)- During treatment	0	0	0	0
Major adverse cardiovascular events according to the CV-EAC- During treatment	0	0	0	1
Any other significant AE- During treatment	0	0	0	0
Subjects with any AE- follow-up	12	8	20	22
Any AE with outcome of death- follow-up	1	0	1	0
Any SAE (including events with outcome of death)- follow-up	3	0	3	3
Any AE related to investigational product (investigator assessment)- follow-up	2	0	2	1
Any AE of severe intensity- follow-up	2	0	2	3
Any AESI- follow-up	2	0	2	2
Non-opportunistic serious infections- follow-up	0	0	0	1
Opportunistic infections- follow-up	0	0	0	0
Anaphylaxis- follow-up	0	0	0	0
Malignancy- follow-up	0	0	0	0
Herpes zoster- follow-up	2	0	2	1
Tuberculosis/LTB- follow-up	0	0	0	0
Influenza- follow-up	0	0	0	0
Vasculitis (non-SLE)- follow-up	0	0	0	0
Major adverse cardiovascular events according to the CV-EAC- follow-up	0	0	0	0
Any other significant AE- follow-up	0	0	0	0

No statistical analysis provided for Number of subjects with adverse events

4. Other Pre-specified Outcome Measure: Number of subjects with suicidal ideation and behavior and suicide attempts via Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline, treatment and follow up (an average of 60 weeks) ]

Measure Type	Other Pre-specified
Measure Name	Number of subjects with suicidal ideation and behavior and suicide attempts via Columbia-Suicide Severity Rating Scale (C-SSRS)
Measure Description	The C-SSRS was used to assess the suicidal ideation and behavior and suicide attempts on a graded scale from 1 to 5. 1 indicates as low suicidal and 5 as high suicidal behavior.
Time Frame	Baseline, treatment and follow up (an average of 60 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.
Full analysis set (FAS): The FAS included all subjects who received at least one dose of study treatment and were analyzed according to randomized treatment (mITT principle). Here, number analyzed in each row signifies only the subjects with available data that were analyzed for each parameter/ timeframe.

Reporting Groups

	Description
Anifrolumab - Basic Regimen	Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Anifrolumab - Intensified Regimen	Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
All Anifrolumab	This arm comprises Anifrolumab - Basic Regimen and Anifrolumab - Intensified Regimen. Anifrolumab - Basic Regimen: Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112. Anifrolumab - Intensified Regimen: Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Placebo	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.

Measured Values

	Anifrolumab - Basic Regimen	Anifrolumab - Intensified Regimen	All Anifrolumab	Placebo
Number of Participants Analyzed [units:participants]	45	51	96	49
Number of subjects with suicidal ideation and behavior and suicide attempts via Columbia-Suicide Severity Rating Scale (C-SSRS) [units: Participants]
Suicidal attempts: Baseline	0	0	0	0
Suicidal attempts: Treatment	0	0	0	0
Suicidal attempts: Follow up	0	0	0	0
Suicidal behaviour: Baseline	0	0	0	0
Suicidal behaviour: Treatment	0	0	0	0
Suicidal behaviour: Follow up	0	0	0	0
Suicidal ideation: Baseline	0	2	2	4
Suicidal ideation: Treatment	0	0	0	2
Suicidal ideation: Follow up	0	0	0	0

No statistical analysis provided for Number of subjects with suicidal ideation and behavior and suicide attempts via Columbia-Suicide Severity Rating Scale (C-SSRS)

5. Other Pre-specified Outcome Measure: Total score of Personal Health Questionnaire Depression Scale-8 (PHQD-8) [ Time Frame: Baseline, Week 12, Week 24, Week 36, Week 52, Week 60 ]

Measure Type	Other Pre-specified
Measure Name	Total score of Personal Health Questionnaire Depression Scale-8 (PHQD-8)
Measure Description	PHQ-8 is a 8-item self-report scale, all items are rated on a score of 0-3, for a total range of 0-24. PHQ-8 assesses symptoms of depression over the previous 2 weeks. Higher scores indicate more depressive symptoms.
Time Frame	Baseline, Week 12, Week 24, Week 36, Week 52, Week 60
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.
Full analysis set (FAS): The FAS included all subjects who received at least one dose of study treatment and were analyzed according to randomized treatment (mITT principle). Here, number analyzed in each row signifies only the subjects with available data that were analyzed for each timeframe.

Reporting Groups

	Description
Anifrolumab - Basic Regimen	Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Anifrolumab - Intensified Regimen	Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
All Anifrolumab	This arm comprises Anifrolumab - Basic Regimen and Anifrolumab - Intensified Regimen. Anifrolumab - Basic Regimen: Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112. Anifrolumab - Intensified Regimen: Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Placebo	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.

Measured Values

	Anifrolumab - Basic Regimen	Anifrolumab - Intensified Regimen	All Anifrolumab	Placebo
Number of Participants Analyzed [units:participants]	45	51	96	49
Total score of Personal Health Questionnaire Depression Scale-8 (PHQD-8) [units: Score on a scale] Mean (Standard Deviation)
Baseline	5.1 (4.34)	4.3 (4.05)	4.6 (4.18)	5.8 (4.54)
Week 12	3.4 (3.88)	3.1 (3.56)	3.2 (3.68)	5.1 (4.84)
Week 24	2.7 (2.41)	2.5 (3.18)	2.6 (2.86)	4.9 (5.10)
Week 36	3.3 (4.04)	2.5 (3.22)	2.8 (3.63)	3.5 (2.73)
Week 52	2.3 (3.44)	3.4 (5.24)	2.9 (4.51)	4.2 (3.30)
Week 60	3.3 (4.80)	5.6 (7.01)	4.6 (6.06)	4.6 (2.07)

No statistical analysis provided for Total score of Personal Health Questionnaire Depression Scale-8 (PHQD-8)

6. Other Pre-specified Outcome Measure: Extra-renal flares using Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI 2K) based Flare Assessment Instrument [ Time Frame: From baseline up to week 112 ]

Measure Type	Other Pre-specified
Measure Name	Extra-renal flares using Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI 2K) based Flare Assessment Instrument
Measure Description	Flare will be defined as any one criterion present in either the Mild/Moderate Flare and/or Severe Flare categories. New or worsened manifestation should only be reported for manifestations of SLE. The SLEDAI-2K score range is 0 to 105 with higher scores representing increased disease activity. Mild/ Moderate flare defined as change in non-renal components of the SLEDAI-2K instrument score of ≥3 but <7 points compared to previous visit. Severe Flare defined as change in non-renal components of the SLEDAI-2K instrument score by ≥7 points compared to previous visit. The flare rate per subject year is defined as the number of subjects with a respective flare divided by the sum of exposure time in days for all subjects in the analysis set multiplied by 365.25.
Time Frame	From baseline up to week 112
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.
Full analysis set (FAS): The FAS included all subjects who received at least one dose of study treatment and were analyzed according to randomized treatment (mITT principle). Here, number analyzed in each row signifies only the subjects with available data that were analyzed for each parameter

Reporting Groups

	Description
Anifrolumab - Basic Regimen	Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Anifrolumab - Intensified Regimen	Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
All Anifrolumab	This arm comprises Anifrolumab - Basic Regimen and Anifrolumab - Intensified Regimen. Anifrolumab - Basic Regimen: Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112. Anifrolumab - Intensified Regimen: Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Placebo	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.

Measured Values

	Anifrolumab - Basic Regimen	Anifrolumab - Intensified Regimen	All Anifrolumab	Placebo
Number of Participants Analyzed [units:participants]	45	51	96	49
Extra-renal flares using Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI 2K) based Flare Assessment Instrument [units: Flare rate per subject year]
Mild/moderate: All flares	0.019	0.016	0.017	0.016
Mild/moderate: On-treatment	0.017	0.012	0.014	0.010
Mild/moderate: Off-treatment	0.002	0.003	0.003	0.006
Severe: All flares	0.007	0.001	0.003	0.006
Severe: On-treatment	0.004	0.00	0.002	0.004
Severe: Off-treatment	0.003	0.001	0.002	0.002

No statistical analysis provided for Extra-renal flares using Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI 2K) based Flare Assessment Instrument

Serious Adverse Events

Time Frame	From screening (Day-30 to -1) period until follow-up (Week 112).
Additional Description	No text entered.

Reporting Groups

	Description
Anifrolumab - Basic Regimen- Treatment Period	Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Anifrolumab - Intensified Regimen- Treatment Period	Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
All Anifrolumab- Treatment Period	This arm comprises Anifrolumab - Basic Regimen and Anifrolumab - Intensified Regimen. Anifrolumab - Basic Regimen: Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112. Anifrolumab - Intensified Regimen: Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Placebo- Treatment Period	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.
Anifrolumab - Basic Regimen- Follow up	Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112
Anifrolumab - Intensified Regimen- Follow up	Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
All Anifrolumab- Follow up	This arm comprises Anifrolumab - Basic Regimen and Anifrolumab - Intensified Regimen. Anifrolumab - Basic Regimen: Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112. Anifrolumab - Intensified Regimen: Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Placebo- Follow up	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.

Serious Adverse Events

Anifrolumab - Basic Regimen- Treatment Period

Anifrolumab - Intensified Regimen- Treatment Period

All Anifrolumab- Treatment Period

Placebo- Treatment Period

Anifrolumab - Basic Regimen- Follow up

Anifrolumab - Intensified Regimen- Follow up

All Anifrolumab- Follow up

Placebo- Follow up

Total, serious adverse events

# participants affected / at risk

10/45 (22.22%)

9/51 (17.65%)

19/96 (19.79%)

8/49 (16.33%)

3/45 (6.67%)

0/51 (0.00%)

3/96 (3.13%)

3/49 (6.12%)

Infections and infestations

Herpes zoster¹

# participants affected / at risk

3/45 (6.67%)

3/51 (5.88%)

6/96 (6.25%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Influenza¹

# participants affected / at risk

1/45 (2.22%)

1/51 (1.96%)

2/96 (2.08%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Abscess bacterial¹

# participants affected / at risk

1/45 (2.22%)

0/51 (0.00%)

1/96 (1.04%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Pyelonephritis acute¹

# participants affected / at risk

1/45 (2.22%)

0/51 (0.00%)

1/96 (1.04%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Varicella zoster pneumonia¹

# participants affected / at risk

0/45 (0.00%)

1/51 (1.96%)

1/96 (1.04%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Atypical pneumonia¹

# participants affected / at risk

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

1/49 (2.04%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Histoplasmosis disseminated¹

# participants affected / at risk

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

1/49 (2.04%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Meningitis¹

# participants affected / at risk

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

1/49 (2.04%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Otitis externa bacterial¹

# participants affected / at risk

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

1/49 (2.04%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Pneumonia¹

# participants affected / at risk

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

1/49 (2.04%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Endometrial adenocarcinoma¹

# participants affected / at risk

0/45 (0.00%)

1/51 (1.96%)

1/96 (1.04%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Blood and lymphatic system disorders

Febrile neutropenia¹

# participants affected / at risk

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

1/49 (2.04%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Cardiac disorders

Lupus endocarditis¹

# participants affected / at risk

1/45 (2.22%)

0/51 (0.00%)

1/96 (1.04%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Cardiac disorders

Acute myocardial infarction¹

# participants affected / at risk

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

1/49 (2.04%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Respiratory, thoracic and mediastinal disorders

Interstitial lung disease¹

# participants affected / at risk

0/45 (0.00%)

1/51 (1.96%)

1/96 (1.04%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹

# participants affected / at risk

0/45 (0.00%)

1/51 (1.96%)

1/96 (1.04%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Musculoskeletal and connective tissue disorders

Systemic lupus erythematosus¹

# participants affected / at risk

1/45 (2.22%)

0/51 (0.00%)

1/96 (1.04%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Renal and urinary disorders

Lupus nephritis¹

# participants affected / at risk

1/45 (2.22%)

1/51 (1.96%)

2/96 (2.08%)

1/49 (2.04%)

1/45 (2.22%)

0/51 (0.00%)

1/96 (1.04%)

0/49 (0.00%)

Renal and urinary disorders

Proteinuria¹

# participants affected / at risk

0/45 (0.00%)

1/51 (1.96%)

1/96 (1.04%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Renal and urinary disorders

Acute kidney injury¹

# participants affected / at risk

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

1/49 (2.04%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Renal and urinary disorders

Nephrotic syndrome¹

# participants affected / at risk

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

1/49 (2.04%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

General disorders

Chest pain¹

# participants affected / at risk

0/45 (0.00%)

1/51 (1.96%)

1/96 (1.04%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

General disorders

Malaise¹

# participants affected / at risk

1/45 (2.22%)

0/51 (0.00%)

1/96 (1.04%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

General disorders

Pyrexia¹

# participants affected / at risk

0/45 (0.00%)

1/51 (1.96%)

1/96 (1.04%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Injury, poisoning and procedural complications

Infusion related reaction¹

# participants affected / at risk

1/45 (2.22%)

0/51 (0.00%)

1/96 (1.04%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Injury, poisoning and procedural complications

Tibia fracture¹

# participants affected / at risk

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

1/49 (2.04%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Varicella¹

# participants affected / at risk

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

1/49 (2.04%)

Cardiac disorders

Congestive cardiomyopathy¹

# participants affected / at risk

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

1/49 (2.04%)

Nervous system disorders

Peripheral sensorimotor neuropathy¹

# participants affected / at risk

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

1/49 (2.04%)

Nervous system disorders

Hypoaesthesia¹

# participants affected / at risk

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

1/45 (2.22%)

0/51 (0.00%)

1/96 (1.04%)

0/49 (0.00%)

Nervous system disorders

Nervous system disorder¹

# participants affected / at risk

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

1/45 (2.22%)

0/51 (0.00%)

1/96 (1.04%)

0/49 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 22.1

Other Adverse Events

Time Frame	From screening (Day-30 to -1) period until follow-up (Week 112).
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Anifrolumab - Basic Regimen- Treatment Period	Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Anifrolumab - Intensified Regimen- Treatment Period	Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
All Anifrolumab- Treatment Period	This arm comprises Anifrolumab - Basic Regimen and Anifrolumab - Intensified Regimen. Anifrolumab - Basic Regimen: Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112. Anifrolumab - Intensified Regimen: Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Placebo- Treatment Period	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.
Anifrolumab - Basic Regimen- Follow up	Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112
Anifrolumab - Intensified Regimen- Follow up	Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
All Anifrolumab- Follow up	This arm comprises Anifrolumab - Basic Regimen and Anifrolumab - Intensified Regimen. Anifrolumab - Basic Regimen: Subjects were administered with lower dose of Anifrolumab intravenously (IV) every 4 weeks (Q4W) from Week 0 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112. Anifrolumab - Intensified Regimen: Subjects were administered with higher dose of Anifrolumab IV Q4W for first 3 doses followed by lower dose from Week 12 to Week 100, in addition to pre-specified standard of care (SOC) which continued until Week 112.
Placebo- Follow up	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.

Other Adverse Events

Anifrolumab - Basic Regimen- Treatment Period

Anifrolumab - Intensified Regimen- Treatment Period

All Anifrolumab- Treatment Period

Placebo- Treatment Period

Anifrolumab - Basic Regimen- Follow up

Anifrolumab - Intensified Regimen- Follow up

All Anifrolumab- Follow up

Placebo- Follow up

Total, other (not including serious) adverse events

# participants affected / at risk

31/45 (68.89%)

39/51 (76.47%)

70/96 (72.92%)

33/49 (67.35%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Urinary tract infection¹

# participants affected / at risk

10/45 (22.22%)

6/51 (11.76%)

16/96 (16.67%)

5/49 (10.20%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Nasopharyngitis¹

# participants affected / at risk

6/45 (13.33%)

9/51 (17.65%)

15/96 (15.63%)

9/49 (18.37%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Upper respiratory tract infection¹

# participants affected / at risk

8/45 (17.78%)

7/51 (13.73%)

15/96 (15.63%)

8/49 (16.33%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Bronchitis¹

# participants affected / at risk

4/45 (8.89%)

7/51 (13.73%)

11/96 (11.46%)

6/49 (12.24%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Herpes zoster¹

# participants affected / at risk

6/45 (13.33%)

4/51 (7.84%)

10/96 (10.42%)

4/49 (8.16%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Pharyngitis¹

# participants affected / at risk

3/45 (6.67%)

4/51 (7.84%)

7/96 (7.29%)

2/49 (4.08%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Oral herpes¹

# participants affected / at risk

3/45 (6.67%)

3/51 (5.88%)

6/96 (6.25%)

2/49 (4.08%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Herpes simplex¹

# participants affected / at risk

3/45 (6.67%)

2/51 (3.92%)

5/96 (5.21%)

2/49 (4.08%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Influenza¹

# participants affected / at risk

1/45 (2.22%)

4/51 (7.84%)

5/96 (5.21%)

1/49 (2.04%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Psychiatric disorders

Depression¹

# participants affected / at risk

1/45 (2.22%)

0/51 (0.00%)

1/96 (1.04%)

3/49 (6.12%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Nervous system disorders

Headache¹

# participants affected / at risk

2/45 (4.44%)

3/51 (5.88%)

5/96 (5.21%)

4/49 (8.16%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Vascular disorders

Hypertension¹

# participants affected / at risk

0/45 (0.00%)

2/51 (3.92%)

2/96 (2.08%)

3/49 (6.12%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Respiratory, thoracic and mediastinal disorders

Cough¹

# participants affected / at risk

4/45 (8.89%)

3/51 (5.88%)

7/96 (7.29%)

4/49 (8.16%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain¹

# participants affected / at risk

0/45 (0.00%)

1/51 (1.96%)

1/96 (1.04%)

3/49 (6.12%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Gastrointestinal disorders

Diarrhoea¹

# participants affected / at risk

3/45 (6.67%)

4/51 (7.84%)

7/96 (7.29%)

10/49 (20.41%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Gastrointestinal disorders

Nausea¹

# participants affected / at risk

1/45 (2.22%)

4/51 (7.84%)

5/96 (5.21%)

2/49 (4.08%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Gastrointestinal disorders

Dyspepsia¹

# participants affected / at risk

2/45 (4.44%)

0/51 (0.00%)

2/96 (2.08%)

4/49 (8.16%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Gastrointestinal disorders

Vomiting¹

# participants affected / at risk

1/45 (2.22%)

1/51 (1.96%)

2/96 (2.08%)

4/49 (8.16%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Gastrointestinal disorders

Abdominal pain¹

# participants affected / at risk

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

4/49 (8.16%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Infections and infestations

Viral upper respiratory tract infection¹

# participants affected / at risk

1/45 (2.22%)

3/51 (5.88%)

4/96 (4.17%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

Metabolism and nutrition disorders

Hyperglycaemia¹

# participants affected / at risk

1/45 (2.22%)

3/51 (5.88%)

4/96 (4.17%)

0/49 (0.00%)

0/45 (0.00%)

0/51 (0.00%)

0/96 (0.00%)

0/49 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 22.1

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: The submission/document contains trade secrets and confidential commercial information, disclosure of which is prohibited without providing advance notice to AstraZeneca and opportunity to object.

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
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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

Protocol
Download
SAP
Download
CSR Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

AstraZeneca AB

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Protocol

SAP

CSR Synopsis

Trial Results Summaries