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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02547922
• Collaborator: Parexel (Industry)
• Enrollment: 147
• Locations: 80
• Arms: 3
• Actual Duration (Months): 62.5
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of an intravenous treatment regimen of two doses of anifrolumab versus placebo in adult subjects with active proliferative lupus nephritis (LN).

Condition or Disease	Intervention/Treatment	Phase
Lupus Nephritis	Biological: Anifrolumab; Drug: Placebo	Phase 2

Detailed Description

This is a Phase 2, multicentre, multinational, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of two intravenous (IV) treatment regimens of anifrolumab versus placebo while taking standard of care (SOC) treatment with mycophenolate mofetil (MMF) and corticosteroids in adult subjects with active proliferative lupus nephritis (LN).

Study Design

• Study Type: Interventional
• Actual Enrollment: 147 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Nov 4, 2015
• Actual Primary Completion Date: Nov 26, 2019
• Actual Study Completion Date: Jan 18, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anifrolumab - Lower Dose Anifrolumab - Lower Dose	Biological: 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: 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

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in 24-hour Urine Protein to Creatinine Ratio (UPCR) [From Week 1 (Baseline) up to Week 52]

   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.

Secondary Outcome Measures

1. Proportion of Subjects Achieving the Composite Endpoint Complete Renal Response (CRR) [Week 52]

   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.

Other Outcome Measures

1. Number of Subjects With Adverse Events [From screening (Day-30 to -1) period until the follow-up period (Week 112)]

   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.

2. Number of Subjects With Suicidal Ideation and Behavior and Suicide Attempts Via Columbia-Suicide Severity Rating Scale (C-SSRS) [Baseline, treatment and follow up (an average of 60 weeks)]

   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.

3. Total Score of Personal Health Questionnaire Depression Scale-8 (PHQD-8) [Baseline, Week 12, Week 24, Week 36, Week 52, Week 60]

   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.

4. Extra-renal Flares Using Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI 2K) Based Flare Assessment Instrument [From baseline up to week 112]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Main 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:

3. Positive antinuclear antibody (ANA) test (1:40 or higher) or

4. Elevated anti-dsDNA antibodies at screening (reported as equivocal or positive results), as per the centrallaboratory; or

5. Anti-Smith antibody at screening elevated to above normal (ie, positive or equivocal results) as per the central laboratory

6. 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:

7. Urine protein to creatinine ratio >1 gm/gm (113.17 mg/mmol), obtained on a 24-hour urine collection at screening

8. Estimated glomerular filtration rate ≥35 mL/min/1.73 m2

9. Must not have active or latent TB on either chest radiograph or by Quantiferon gold test

10. 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

6. Oral corticosteroids >0.5 mg/kg/day for more than 8 weeks or

7. Oral or IV pulse methylprednisolone >3.0 gm (cumulative dose) or

8. IV cyclophosphamide >2 pulses of high-dose (≥0.5 gm/m2) or >4 doses of low dose (500 mg every 2 weeks) or

9. Average MMF >2.5 gm/day (>1800 mg/day of enteric-coated mycophenolate sodium) for more than 8 weeks or

10. Tacrolimus >4 mg/day for more than 8 weeks

11. Major surgery within 8 weeks before signing the ICF or major surgery planned during the study period

12. 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

13. Confirmed positive test for hepatitis B or hepatitis C

14. Any severe herpes infection at any time prior to randomization

15. Opportunistic infection requiring hospitalisation or parenteral antimicrobial treatment within 3 years prior to randomization (vaginal, oral and skin candidiasis is not an exclusionreason).

16. History of cancer, apart from:

17. Squamous or basal cell carcinoma of the skin that has been successfully treated

18. Cervical cancer in situ that has been successfully treated

19. 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.

20. During screening (within 30 days before Day 1 [Week 0 visit]), any of the following:

21. Aspartate transaminase (AST) >2.5×upper limit of normal (ULN)

22. Alanine transaminase (ALT) >2.5×ULN

23. Total bilirubin >ULN (unless due to Gilbert's syndrome [based on Investigator's judgement])

24. Glycosylated haemoglobin (HbA1c) >8% (or >0.08) at screening (diabetic subjects only)

25. Neutrophil count <1x103/μL (or <1.0 GI/L)

26. Platelet count <25x103/μL (or <25 GI/L)

27. Haemoglobin <8 g/dL (or <80 g/L).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Glendale	Arizona	United States	85306
2	Research Site	Phoenix	Arizona	United States	85032
3	Research Site	La Jolla	California	United States	92037-0706
4	Research Site	Los Angeles	California	United States	90095-1670
5	Research Site	Thousand Oaks	California	United States	91360
6	Research Site	Aurora	Colorado	United States	80045
7	Research Site	DeBary	Florida	United States	32713
8	Research Site	Boston	Massachusetts	United States	02118
9	Research Site	Newark	New Jersey	United States	07103-2499
10	Research Site	Bronx	New York	United States	10457
11	Research Site	Great Neck	New York	United States	11021
12	Research Site	New Hyde Park	New York	United States	11042
13	Research Site	New York	New York	United States	10016
14	Research Site	New York	New York	United States	10029
15	Research Site	Columbus	Ohio	United States	43210
16	Research Site	Oklahoma City	Oklahoma	United States	73104
17	Research Site	Memphis	Tennessee	United States	38119
18	Research Site	Buenos Aires		Argentina	C1015ABO
19	Research Site	Cordoba		Argentina	5016
20	Research Site	Rosario		Argentina	S2000PBJ
21	Research Site	Adelaide		Australia	5000
22	Research Site	Clayton		Australia	VIC 3168
23	Research Site	Parkville		Australia	3050
24	Research Site	Westmead		Australia	2145
25	Research Site	Brussels		Belgium	1070
26	Research Site	Bruxelles		Belgium	1200
27	Research Site	Leuven		Belgium	3000
28	Research Site	Liege		Belgium	B-4000
29	Research Site	Bordeaux Cedex		France	33076
30	Research Site	Marseille		France	13005
31	Research Site	Paris Cedex 14		France	75013
32	Research Site	Strasbourg		France	67098
33	Research Site	Toulouse		France	31059
34	Research Site	Berlin		Germany	10117
35	Research Site	Kiel		Germany	24105
36	Research Site	Budapest		Hungary	1097
37	Research Site	Debrecen		Hungary	4032
38	Research Site	Kaposvár		Hungary	7400
39	Research Site	Szeged		Hungary	6725
40	Research Site	Milano		Italy	20132
41	Research Site	Padova		Italy	35128
42	Research Site	Pisa		Italy	56126
43	Research Site	Reggio Emilia		Italy	42100
44	Research Site	Gwangju		Korea, Republic of	501-757
45	Research Site	Seoul		Korea, Republic of	05505
46	Research Site	Seoul		Korea, Republic of	150-713
47	Research Site	Suwon-si		Korea, Republic of	16499
48	Research Site	Chihuahua		Mexico	31000
49	Research Site	Guadalajara		Mexico	44160
50	Research Site	Guadalajara		Mexico	44280
51	Research Site	Mexico		Mexico	14080
52	Research Site	San Luis Potosí		Mexico	78213
53	Research Site	Arequipa		Peru	AREQUIPA54
54	Research Site	Lima		Peru	L14
55	Research Site	Lima		Peru	L34
56	Research Site	Lima		Peru	LIMA 01
57	Research Site	Lima		Peru	LIMA 31
58	Research Site	Lima		Peru	LIMA 32
59	Research Site	Lima		Peru	LIMA 33
60	Research Site	Lima		Peru	Lima-1
61	Research Site	Lima		Peru
62	Research Site	Krakow		Poland	31-066
63	Research Site	Warszawa		Poland	02-637
64	Research Site	Łódź		Poland	92-213
65	Research Site	Orenburg		Russian Federation	460018
66	Research Site	Saint Petersburg		Russian Federation	197022
67	Research Site	Saint Petersburg		Russian Federation	197089
68	Research Site	Belgrade		Serbia	11000
69	Research Site	Belgrade		Serbia	1100
70	Research Site	Nis		Serbia	18000
71	Research Site	Novi Sad		Serbia	21000
72	Research Site	Barcelona		Spain	08035
73	Research Site	Barcelona		Spain	08036
74	Research Site	Changhua City		Taiwan	50006
75	Research Site	Kaohsiung		Taiwan	80756
76	Research Site	Taichung		Taiwan	40447
77	Research Site	Taichung		Taiwan	40705
78	Research Site	Taipei		Taiwan	100
79	Research Site	Taoyuan City		Taiwan	333
80	Research Site	London		United Kingdom	E1 1BB

Sponsors and Collaborators

• AstraZeneca
• Parexel

Investigators

• Study Director: AstraZeneca AB, AstraZeneca

Study Documents (Full-Text)

• Study Protocol - Dec 13, 2017
• Statistical Analysis Plan - Mar 24, 2020

More Information

Additional Information:

• Protocol
• SAP
• CSR Synopsis

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02547922
• Other Study ID Numbers: D3461C00007
• First Posted: Sep 14, 2015
• Last Update Posted: Nov 24, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AstraZeneca: lupus, nephritis, randomized, placebo, anifrolumab, safety, efficacy, adult
• Additional relevant MeSH terms: Nephritis; Lupus Nephritis

Study Results

Participant Flow

Recruitment Details	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 Detail	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.

Arm/Group Title	Anifrolumab - Basic Regimen	Anifrolumab - Intensified Regimen	Placebo
Arm/Group Description	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.	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.	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.
Period Title: Overall Study
STARTED	46	52	49
FAS (Full Analysis Set)	45	51	49
COMPLETED	18	28	20
NOT COMPLETED	28	24	29

Baseline Characteristics

Arm/Group Title	Anifrolumab - Basic Regimen	Anifrolumab - Intensified Regimen	Placebo	Total
Arm/Group Description	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.	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.	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.	Total of all reporting groups
Overall Participants	45	51	49	145
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.2 (11.49)	35.0 (10.58)	34.0 (10.18)	34.7 (10.68)
Sex: Female, Male (Count of Participants)
Female	37 82.2%	45 88.2%	38 77.6%	120 82.8%
Male	8 17.8%	6 11.8%	11 22.4%	25 17.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	22 48.9%	23 45.1%	20 40.8%	65 44.8%
Not Hispanic or Latino	23 51.1%	28 54.9%	29 59.2%	80 55.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	3 6.7%	1 2%	0 0%	4 2.8%
Asian	11 24.4%	7 13.7%	10 20.4%	28 19.3%
Native Hawaiian or Other Pacific Islander	1 2.2%	0 0%	0 0%	1 0.7%
Black or African American	2 4.4%	4 7.8%	1 2%	7 4.8%
White	17 37.8%	25 49%	24 49%	66 45.5%
Other	11 24.4%	14 27.5%	14 28.6%	39 26.9%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in 24-hour Urine Protein to Creatinine Ratio (UPCR)
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Anifrolumab - Basic Regimen	Anifrolumab - Intensified Regimen	All Anifrolumab	Placebo
Arm/Group Description	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.	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.	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.	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.
Measure Participants	41	50	91	41
Geometric Mean (95% Confidence Interval) [milligram/milligram (mg/mg)]	0.326	0.285	0.305	0.296

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Anifrolumab, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9052
	Comments	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.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	1.031
	Confidence Interval	(2-Sided) 95%; 0.621 to 1.713
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric mean ratio >1 favours placebo.

2. Secondary Outcome

Title	Proportion of Subjects Achieving the Composite Endpoint Complete Renal Response (CRR)
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

Outcome Measure Data

Analysis Population Description

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)).

Arm/Group Title	Anifrolumab - Basic Regimen	Anifrolumab - Intensified Regimen	All Anifrolumab	Placebo
Arm/Group Description	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.	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.	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.	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.
Measure Participants	45	51	96	49
Responder	16.3	45.5	31.0	31.1
Non-responder	83.7	54.5	69.0	68.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Anifrolumab, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9929
	Comments	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.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in estimates
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -16.92 to 16.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Other Pre-specified Outcome

Title	Number of Subjects With Adverse Events
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)

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Anifrolumab - Basic Regimen	Anifrolumab - Intensified Regimen	All Anifrolumab	Placebo
Arm/Group Description	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.	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.	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.	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.
Measure Participants	45	51	96	49
Subjects with any AE- During treatment	43 95.6%	47 92.2%	90 183.7%	44 30.3%
Subjects with any acute AE- During treatment	11 24.4%	15 29.4%	26 53.1%	14 9.7%
Any AE with outcome of death- During treatment	0 0%	0 0%	0 0%	0 0%
Any SAE (including events with- outcome of death)- During treatment	10 22.2%	9 17.6%	19 38.8%	8 5.5%
Any AE leading to discontinuation of investigational product- During treatment	5 11.1%	6 11.8%	11 22.4%	5 3.4%
Any AE related to investigational product (investigator assessment)- During treatment	24 53.3%	13 25.5%	37 75.5%	16 11%
Any AE of severe intensity- During treatment	6 13.3%	7 13.7%	13 26.5%	8 5.5%
Any AESI- During treatment	12 26.7%	12 23.5%	24 49%	8 5.5%
Non-opportunistic serious infections- During treatment	0 0%	1 2%	1 2%	3 2.1%
Opportunistic infections- During treatment	1 2.2%	0 0%	1 2%	1 0.7%
Anaphylaxis- During treatment	0 0%	0 0%	0 0%	0 0%
Malignancy- During treatment	0 0%	1 2%	1 2%	0 0%
Herpes zoster- During treatment	9 20%	7 13.7%	16 32.7%	4 2.8%
Tuberculosis/LTB (latent tuberculosis)- During treatment	0 0%	0 0%	0 0%	0 0%
Influenza- During treatment	2 4.4%	4 7.8%	6 12.2%	1 0.7%
Vasculitis (non-systemic lupus erythematosus)- During treatment	0 0%	0 0%	0 0%	0 0%
Major adverse cardiovascular events according to the CV-EAC- During treatment	0 0%	0 0%	0 0%	1 0.7%
Any other significant AE- During treatment	0 0%	0 0%	0 0%	0 0%
Subjects with any AE- follow-up	12 26.7%	8 15.7%	20 40.8%	22 15.2%
Any AE with outcome of death- follow-up	1 2.2%	0 0%	1 2%	0 0%
Any SAE (including events with outcome of death)- follow-up	3 6.7%	0 0%	3 6.1%	3 2.1%
Any AE related to investigational product (investigator assessment)- follow-up	2 4.4%	0 0%	2 4.1%	1 0.7%
Any AE of severe intensity- follow-up	2 4.4%	0 0%	2 4.1%	3 2.1%
Any AESI- follow-up	2 4.4%	0 0%	2 4.1%	2 1.4%
Non-opportunistic serious infections- follow-up	0 0%	0 0%	0 0%	1 0.7%
Opportunistic infections- follow-up	0 0%	0 0%	0 0%	0 0%
Anaphylaxis- follow-up	0 0%	0 0%	0 0%	0 0%
Malignancy- follow-up	0 0%	0 0%	0 0%	0 0%
Herpes zoster- follow-up	2 4.4%	0 0%	2 4.1%	1 0.7%
Tuberculosis/LTB- follow-up	0 0%	0 0%	0 0%	0 0%
Influenza- follow-up	0 0%	0 0%	0 0%	0 0%
Vasculitis (non-SLE)- follow-up	0 0%	0 0%	0 0%	0 0%
Major adverse cardiovascular events according to the CV-EAC- follow-up	0 0%	0 0%	0 0%	0 0%
Any other significant AE- follow-up	0 0%	0 0%	0 0%	0 0%

4. Other Pre-specified Outcome

Title	Number of Subjects With Suicidal Ideation and Behavior and Suicide Attempts Via Columbia-Suicide Severity Rating Scale (C-SSRS)
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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Anifrolumab - Basic Regimen	Anifrolumab - Intensified Regimen	All Anifrolumab	Placebo
Arm/Group Description	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.	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.	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.	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.
Measure Participants	45	51	96	49
Suicidal attempts: Baseline	0 0%	0 0%	0 0%	0 0%
Suicidal attempts: Treatment	0 0%	0 0%	0 0%	0 0%
Suicidal attempts: Follow up	0 0%	0 0%	0 0%	0 0%
Suicidal behaviour: Baseline	0 0%	0 0%	0 0%	0 0%
Suicidal behaviour: Treatment	0 0%	0 0%	0 0%	0 0%
Suicidal behaviour: Follow up	0 0%	0 0%	0 0%	0 0%
Suicidal ideation: Baseline	0 0%	2 3.9%	2 4.1%	4 2.8%
Suicidal ideation: Treatment	0 0%	0 0%	0 0%	2 1.4%
Suicidal ideation: Follow up	0 0%	0 0%	0 0%	0 0%

5. Other Pre-specified Outcome

Title	Total Score of Personal Health Questionnaire Depression Scale-8 (PHQD-8)
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Anifrolumab - Basic Regimen	Anifrolumab - Intensified Regimen	All Anifrolumab	Placebo
Arm/Group Description	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.	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.	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.	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.
Measure Participants	45	51	96	49
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)

6. Other Pre-specified Outcome

Title	Extra-renal Flares Using Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI 2K) Based Flare Assessment Instrument
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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Anifrolumab - Basic Regimen	Anifrolumab - Intensified Regimen	All Anifrolumab	Placebo
Arm/Group Description	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.	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.	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.	Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.
Measure Participants	45	51	96	49
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

Adverse Events

Time Frame	From screening (Day-30 to -1) period until follow-up (Week 112).
Arm/Group Title	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
Arm/Group Description	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.		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.		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.		Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.		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		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.		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.		Subjects were administered with placebo every 4 week from Week 0 to Week 100 in addition to SOC which continued until Week 112.
All Cause Mortality
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)		1/45 (2.2%)		0/51 (0%)		1/96 (1%)		0/49 (0%)
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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/45 (22.2%)		9/51 (17.6%)		19/96 (19.8%)		8/49 (16.3%)		3/45 (6.7%)		0/51 (0%)		3/96 (3.1%)		3/49 (6.1%)
Blood and lymphatic system disorders
Febrile neutropenia	0/45 (0%)		0/51 (0%)		0/96 (0%)		1/49 (2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Cardiac disorders
Lupus endocarditis	1/45 (2.2%)		0/51 (0%)		1/96 (1%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Acute myocardial infarction	0/45 (0%)		0/51 (0%)		0/96 (0%)		1/49 (2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Congestive cardiomyopathy	0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		1/49 (2%)
General disorders
Chest pain	0/45 (0%)		1/51 (2%)		1/96 (1%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Malaise	1/45 (2.2%)		0/51 (0%)		1/96 (1%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Pyrexia	0/45 (0%)		1/51 (2%)		1/96 (1%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Infections and infestations
Herpes zoster	3/45 (6.7%)		3/51 (5.9%)		6/96 (6.3%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Influenza	1/45 (2.2%)		1/51 (2%)		2/96 (2.1%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Abscess bacterial	1/45 (2.2%)		0/51 (0%)		1/96 (1%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Pyelonephritis acute	1/45 (2.2%)		0/51 (0%)		1/96 (1%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Varicella zoster pneumonia	0/45 (0%)		1/51 (2%)		1/96 (1%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Atypical pneumonia	0/45 (0%)		0/51 (0%)		0/96 (0%)		1/49 (2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Histoplasmosis disseminated	0/45 (0%)		0/51 (0%)		0/96 (0%)		1/49 (2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Meningitis	0/45 (0%)		0/51 (0%)		0/96 (0%)		1/49 (2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Otitis externa bacterial	0/45 (0%)		0/51 (0%)		0/96 (0%)		1/49 (2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Pneumonia	0/45 (0%)		0/51 (0%)		0/96 (0%)		1/49 (2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Varicella	0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		1/49 (2%)
Injury, poisoning and procedural complications
Infusion related reaction	1/45 (2.2%)		0/51 (0%)		1/96 (1%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Tibia fracture	0/45 (0%)		0/51 (0%)		0/96 (0%)		1/49 (2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus	1/45 (2.2%)		0/51 (0%)		1/96 (1%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial adenocarcinoma	0/45 (0%)		1/51 (2%)		1/96 (1%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Nervous system disorders
Peripheral sensorimotor neuropathy	0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		1/49 (2%)
Hypoaesthesia	0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)		1/45 (2.2%)		0/51 (0%)		1/96 (1%)		0/49 (0%)
Nervous system disorder	0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)		1/45 (2.2%)		0/51 (0%)		1/96 (1%)		0/49 (0%)
Renal and urinary disorders
Lupus nephritis	1/45 (2.2%)		1/51 (2%)		2/96 (2.1%)		1/49 (2%)		1/45 (2.2%)		0/51 (0%)		1/96 (1%)		0/49 (0%)
Proteinuria	0/45 (0%)		1/51 (2%)		1/96 (1%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Acute kidney injury	0/45 (0%)		0/51 (0%)		0/96 (0%)		1/49 (2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Nephrotic syndrome	0/45 (0%)		0/51 (0%)		0/96 (0%)		1/49 (2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	0/45 (0%)		1/51 (2%)		1/96 (1%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Pulmonary embolism	0/45 (0%)		1/51 (2%)		1/96 (1%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Other (Not Including 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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/45 (68.9%)		39/51 (76.5%)		70/96 (72.9%)		33/49 (67.3%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Gastrointestinal disorders
Diarrhoea	3/45 (6.7%)		4/51 (7.8%)		7/96 (7.3%)		10/49 (20.4%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Nausea	1/45 (2.2%)		4/51 (7.8%)		5/96 (5.2%)		2/49 (4.1%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Dyspepsia	2/45 (4.4%)		0/51 (0%)		2/96 (2.1%)		4/49 (8.2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Vomiting	1/45 (2.2%)		1/51 (2%)		2/96 (2.1%)		4/49 (8.2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Abdominal pain	0/45 (0%)		0/51 (0%)		0/96 (0%)		4/49 (8.2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Infections and infestations
Urinary tract infection	10/45 (22.2%)		6/51 (11.8%)		16/96 (16.7%)		5/49 (10.2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Nasopharyngitis	6/45 (13.3%)		9/51 (17.6%)		15/96 (15.6%)		9/49 (18.4%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Upper respiratory tract infection	8/45 (17.8%)		7/51 (13.7%)		15/96 (15.6%)		8/49 (16.3%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Bronchitis	4/45 (8.9%)		7/51 (13.7%)		11/96 (11.5%)		6/49 (12.2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Herpes zoster	6/45 (13.3%)		4/51 (7.8%)		10/96 (10.4%)		4/49 (8.2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Pharyngitis	3/45 (6.7%)		4/51 (7.8%)		7/96 (7.3%)		2/49 (4.1%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Oral herpes	3/45 (6.7%)		3/51 (5.9%)		6/96 (6.3%)		2/49 (4.1%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Herpes simplex	3/45 (6.7%)		2/51 (3.9%)		5/96 (5.2%)		2/49 (4.1%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Influenza	1/45 (2.2%)		4/51 (7.8%)		5/96 (5.2%)		1/49 (2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Viral upper respiratory tract infection	1/45 (2.2%)		3/51 (5.9%)		4/96 (4.2%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	1/45 (2.2%)		3/51 (5.9%)		4/96 (4.2%)		0/49 (0%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Nervous system disorders
Headache	2/45 (4.4%)		3/51 (5.9%)		5/96 (5.2%)		4/49 (8.2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Psychiatric disorders
Depression	1/45 (2.2%)		0/51 (0%)		1/96 (1%)		3/49 (6.1%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	4/45 (8.9%)		3/51 (5.9%)		7/96 (7.3%)		4/49 (8.2%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Oropharyngeal pain	0/45 (0%)		1/51 (2%)		1/96 (1%)		3/49 (6.1%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)
Vascular disorders
Hypertension	0/45 (0%)		2/51 (3.9%)		2/96 (2.1%)		3/49 (6.1%)		0/45 (0%)		0/51 (0%)		0/96 (0%)		0/49 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.