Efficacy and Safety of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02446912
• Collaborator: PRA Health Sciences (Industry)
• Enrollment: 460
• Locations: 146
• Arms: 3
• Actual Duration (Months): 37.3
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.1

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 moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE).

Condition or Disease	Intervention/Treatment	Phase
Active Systemic Lupus Erythematosus	Biological: Anifrolumab; Drug: Placebo	Phase 3

Detailed Description

This is a Phase 3, multicentre, multinational, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of an intravenous treatment regimen of two doses of anifrolumab versus placebo in subjects with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE) while receiving standard of care (SOC) treatment. The study will be performed in adult subjects aged 18 to 70 years of age.

Study Design

• Study Type: Interventional
• Actual Enrollment: 460 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicentre, Randomised, Double-blind, Placebo-controlled, Phase 3 Study Evaluating the Efficacy and Safety of Two Doses of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus
• Actual Study Start Date: Jun 9, 2015
• Actual Primary Completion Date: Jul 17, 2018
• Actual Study Completion Date: Jul 17, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anifrolumab - higher dose Anifrolumab	Biological: Anifrolumab; Anifrolumab IV administration every 4 weeks from Week 0 to Week 48 for a total of 13 doses
Placebo Comparator: Placebo Placebo	Drug: Placebo; Placebo IV administration every 4 weeks from Week 0 to Week 48
Experimental: Anifrolumab - lower dose Anifrolumab	Biological: Anifrolumab; Anifrolumab IV administration every 4 weeks from Week 0 to Week 48 for a total of 13 doses

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index ≥4 (SRI[4]) at Week 52 (Original Analysis With Restricted Medication Rules) [Week 52]

   SRI(4) was defined as meeting all of the following criteria: Reduction from baseline of ≥4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) No new organ systems affected, defined by 1 or more British Isles Lupus Assessment Group (BILAG-2004) A or 2 or more BILAG-2004 B items No worsening from baseline in participants lupus disease activity. Worsening was defined as an increase of ≥0.30 points on a 3-point Physician's Global Assessment (PGA) visual analogue scale (VAS) No discontinuation of investigational product and no use of restricted medications beyond the pre-specified analysis threshold.

Secondary Outcome Measures

1. Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index of ≥4 at Week 52 in the Interferon (IFN) Test-High Sub-Group (Original Analysis With Restricted Medication Rules) [Week 52]

   SRI(4) was defined as meeting all of the following criteria: Reduction from baseline of ≥4 points in the SLEDAI-2K No new organ systems affected, defined by 1 or more BILAG-2004 A or 2 or more BILAG-2004 B No worsening from baseline in participants lupus disease activity. Worsening was defined as an increase of ≥0.30 points on a 3-point PGA VAS No discontinuation of investigational product and no use of restricted medications beyond the pre-specified analysis threshold.

2. Number of Participants Who Achieved and Maintained an Oral Corticosteroid (OCS) Dose of ≤7.5 mg/Day in the Sub-group of Participants With Baseline OCS ≥10 mg/Day (Original Analysis With Restricted Medication Rules) [Week 52]

   Maintained OCS reduction was defined by meeting all the following criteria: Achieve an OCS dose of ≤7.5 mg/day prednisone or equivalent by Week 40 Maintain an OCS dose ≤7.5 mg/day prednisone or equivalent from Week 40 to Week 52 No discontinuation of investigational product and no use of restricted medications beyond the pre-specified analysis threshold.

3. Number of Participants With a ≥50% Reduction in CLASI Activity Score at Week 12 in the Sub-group of Participants With Baseline CLASI Activity Score ≥10 (Original Analysis With Restricted Medication Rules) [Week 12]

   50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score compared to baseline was defined by meeting all of the following criteria: Achieve ≥50% reduction of CLASI activity score at Week 12 compared to baseline No discontinuation of investigational product and no use of restricted medications beyond the pre-specified analysis threshold before assessment.

4. Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index of ≥4 (SRI[4]) at Week 24 (Original Analysis With Restricted Medication Rules) [Week 24]

   SRI(4) was defined as meeting all of the following criteria: Reduction from baseline of ≥4 points in the SLEDAI-2K No new organ systems affected as defined by 1 or more BILAG-2004 A or 2 or more BILAG-2004 B items No worsening from baseline in participants lupus disease activity. Worsening was defined as an increase of ≥0.30 points on a 3-point PGA VAS No discontinuation of investigational product and no use of restricted medications beyond the pre-specified threshold.

5. Annualized Flare Rate [Baseline to Week 52]

   A flare was defined as either 1 or more new British Isle Lupus Assessment Group (BILAG-2004) A or 2 or more new BILAG-2004 B items compared to the previous visit. The occurrence of a new flare was checked for each available visit versus the previous available visit up to Week 52. If no new flares occurred, the number of flares was set to 0. Otherwise all flares were counted leading to the maximum number of flares of 13. The annualized flare rate was calculated as the number of flares divided by the flare exposure time in days multiplied with 365.25 (1 year). The flare exposure time is the time up to Week 52 (date of BILAG-2004 assessment at Week 52) or up to the date of last available BILAG-2004 assessment.

6. Number of Participants Who Met the Criteria for British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response (Original Analysis With Restricted Medication Rules) [Week 52]

   A BICLA responder was achieved if all of the following criteria was met: All criteria related to SRI(4) (please see primary endpoint) plus: Reduction of all baseline BILAG-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by 1 or more BILAG-2004 A or 1 or more new BILAG-2004 B item No discontinuation of investigational product and no use of restricted medications beyond the revised post-hoc analysis threshold before assessment.

7. Number of Participants Reporting One or More Adverse Events (AE) [Baseline to End of Trial (Maximum of 60 weeks)]

   An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. AEs were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose [Week 48]), or until Week 52 for participants who enrolled onto the long term extension (LTE). The reported value is inclusive of serious and non-serious AEs.

8. Number of Participants Reporting One or More Adverse Events of Special Interest (AESI) [Baseline to End of Trial (Maximum of 60 weeks)]

   An AESI is an AE of scientific and medical concern specific to understanding biologics and requires close monitoring and rapid communication by the Investigator to the Sponsor/Sponsor's delegate. An AESI may be serious or nonserious. The events of interest 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, MI, or cardiovascular death). AEs were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose [Week 48]), or until Week 52 for participants who enrolled onto the long term extension (LTE).

9. Number of Participants With Markedly Abnormal Vital Signs [Baseline to End of Trial (Maximum of 60 weeks)]

   Vital signs included oral temperature, blood pressure (BP), pulse rate, and respiratory rate. Vital signs were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose [Week 48]), or until Week 52 for participants who enrolled onto the long term extension (LTE).

10. Number of Participants With Markedly Abnormal Physical Examinations [Baseline to End of Trial (Maximum of 60 weeks)]

    Physical examinations included height and weight. Participants were weighed at each study visit and any medically significant changes were reported. Physical examination values were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose [Week 48]), or until Week 52 for participants who enrolled onto the long term extension (LTE).

11. Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Scores [Baseline to Week 52]

    ECGs documented the date, time, heart rate, QRS duration, PR interval, RR interval, QT, and corrected QT interval, which were calculated using the Fridericia formula. The investigator judged the overall interpretation as normal or abnormal, and if abnormal it was decided as to whether or not the abnormality was clinically significant or not clinically significant.

12. Number of Participants With Mild To Moderate Lupus Flare Evaluated by Modified Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI Flare Index [Baseline to End of Trial (Maximum of 60 weeks)]

    The modified SELENA flare index was completed by the Investigator or delegated/qualified physician. Assessment of flares were scored in comparison to the participant's previous visit and should only include findings which, in the opinion of the Investigator, are due to systemic lupus erythematosus (SLE) disease activity within that timeframe. Flare was defined as any 1 criterion present in either the Mild/Moderate Flare or Severe Flare categories. Number of flares were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose [Week 48]), or until Week 52 for participants who enrolled onto the long term extension (LTE).

13. Number of Participants With Markedly Abnormal Laboratory Tests [Baseline to End of Trial (Maximum of 60 weeks)]

    Laboratory tests were collected at central clinical laboratories and included hematology, serum chemistry and urinalysis tests. Laboratory values were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose [Week 48]), or until Week 52 for participants who enrolled onto the long term extension (LTE).

14. Number of Participants With Suicidal Ideation or Behaviour Assessed Via the Columbia Suicide Severity Rating Scale (C-SSRS) [Baseline to Week 52]

    The C-SSRS is an assessment tool that evaluates suicidal ideation and behavior. Number of participants with suicidal ideation or behavior was defined as the number of participants who answered "yes" at any time during the treatment period (Baseline to Week 52) to one of the 10 categories: Category 1: Wish to be dead Category 2: Non-specific active suicidal thoughts Category 3: Active suicidal ideation with any methods (not plan) without intent to act Category 4: Active suicidal ideation with some intent to act, without specific plan Category 5: Active suicidal ideation with specific plan and intent Category 6: Preparatory acts or behavior Category 7: Aborted attempt Category 8: Interrupted attempt Category 9: Actual attempt (non-fatal) Category 10: Completed suicide

15. Change From Baseline in Personal Health Questionnaire Depression Scale-8 (PHQ-8) Score [Baseline to Week 52]

    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. A negative change from baseline score indicates improvement in symptoms.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Aged 18 through 70 years at the time of screening

2. Diagnosis of paediatric or adult SLE with a diagnosis of SLE according to the ACR 1982 revised criteria ≥24 weeks prior to signing the Informed Consent form (ICF)

3. Currently receiving at least 1 of the following:

4. Where prednisone is the single standard of care medication (ie, the subject is not concurrently receiving any medication listed in inclusion criterion 3(c)), a dose of oral prednisone ≥7.5 mg/day but ≤40 mg/day (or prednisone equivalent) for a minimum of 8 weeks prior to Day 1. In addition, the dose of oral prednisone or prednisone equivalent the subject is taking must be stable for a minimum of 2 weeks prior to randomisation.

5. Where prednisone is not the single standard of care medication (ie, the subject is concurrently receiving at least one medication listed in inclusion criterion 3(c)), a dose of oral prednisone (≤40 mg/day) (or prednisone equivalent) for a minimum of 2 weeks prior to signing of the ICF. In addition, the dose of oral prednisone or prednisone equivalent the subject is taking must be stable for a minimum of 2 weeks prior to randomisation.

6. Any of the following medications administered for a minimum of 12 weeks prior to signing the informed consent, and at a stable dose for a minimum of 8 weeks prior to signing the informed consent through Day 1:

(i) Azathioprine ≤200 mg/day (ii) Antimalarial (eg, chloroquine, hydroxychloroquine, quinacrine) (iii) Mycophenolate mofetil ≤2 g/day or mycophenolic acid ≤1.44 g/day (iv) Oral, subcutaneous (SC), or intramuscular methotrexate ≤25 mg/week (v) Mizoribine ≤150 mg/day

1. Fulfils at least 4 of the 11 ACR modified 1982 classification criteria for SLE, at least 1 of which must be:

2. Positive antinuclear antibody (ANA) test at screening by immunofluorescent assay (IFA) at the central laboratory with titre ≥1:80; OR

3. Anti-dsDNA antibodies at screening elevated to above normal (including indeterminante), as per the central laboratory; OR

4. Anti-Smith (anti-Sm) antibody at screening elevated to above normal as per the central laboratory.

5. At Screening, Disease Activity Adjudication Group confirmation of:

SLEDAI-2K Criteria: SLEDAI-2K score ≥6 points and "Clinical" SLEDAI-2K score ≥4 points. The "Clinical" SLEDAI-2K is the SLEDAI-2K assessment score without the inclusion of points attributable to any urine or laboratory results including immunologic measures.

1. Must not have active or latent TB on either chest radiograph or by quantiferon gold test

2. Day 1 "Clinical" SLEDAI-2K score ≥4 points

3. OCS dose stable for at least 2 weeks prior to randomisation

4. Stable SLE SOC treatment at the time of randomisation

5. Women of child-bearing potential must have a negative serum β-hCG test and negative urine pregnancy test at randomisation (Day 1) prior to administration of investigational product

Exclusion Criteria:

1. Receipt of any investigational product (small molecule or biologic agent) within 4 weeks or 5 half-lives prior to signing of the ICF, whichever is greater

2. Receipt of any of the following:

(a) Intra-articular, intramuscular or IV glucocorticosteroids within 6 weeks prior to Day 1

1. History of, or current diagnosis of, a clinically significant non SLE-related vasculitis syndrome.

2. Active severe or unstable neuropsychiatric SLE

3. Active severe SLE-driven renal disease

4. Diagnosis (within 1 year of signing the ICF) of mixed connective tissue disease or any history of overlap syndromes of SLE or SSc.

5. History of, or current, inflammatory joint or skin disease other than SLE

6. History of any non-SLE disease that has required treatment with oral or parenteral corticosteroids for more than 2 weeks within the last 24 weeks prior to signing the ICF

7. Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the subject to infection, or a positive result for human immunodeficiency virus (HIV) infection confirmed by central laboratory at screening. Subjects refusing HIV testing during the screening period will not be eligible for study participation

8. Confirmed positive test for hepatitis B or hepatitis C

9. Any severe herpes infection at any time prior to Week 0 (Day 1)

10. Opportunistic infection requiring hospitalisation or intravenous antimicrobial treatment within 3 years prior to randomization

11. History of cancer, apart from:

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

13. Cervical cancer in situ that has been successfully treated

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35233
2	Research Site	El Cajon	California	United States	91942-3191
3	Research Site	La Jolla	California	United States	92037-0706
4	Research Site	Los Alamitos	California	United States	90720
5	Research Site	Thousand Oaks	California	United States	91360
6	Research Site	Aurora	Colorado	United States	80045
7	Research Site	Aventura	Florida	United States	33180
8	Research Site	Miami	Florida	United States	33136
9	Research Site	Orlando	Florida	United States	32804
10	Research Site	Orlando	Florida	United States	32806
11	Research Site	Ormond Beach	Florida	United States	32174
12	Research Site	Plantation	Florida	United States	33324
13	Research Site	Tampa	Florida	United States	33614
14	Research Site	Vero Beach	Florida	United States	32960
15	Research Site	Decatur	Georgia	United States	30033
16	Research Site	Lawrenceville	Georgia	United States	30046
17	Research Site	Marietta	Georgia	United States	30060
18	Research Site	Boise	Idaho	United States	83712
19	Research Site	Idaho Falls	Idaho	United States	83404
20	Research Site	Baton Rouge	Louisiana	United States	70809
21	Research Site	Hagerstown	Maryland	United States	21502
22	Research Site	Hagerstown	Maryland	United States	21740
23	Research Site	Grand Rapids	Michigan	United States	49546
24	Research Site	Minneapolis	Minnesota	United States	55455-0341
25	Research Site	Nashua	New Hampshire	United States	03060
26	Research Site	Freehold	New Jersey	United States	07728
27	Research Site	Great Neck	New York	United States	11021
28	Research Site	New Hyde Park	New York	United States	11042
29	Research Site	Charlotte	North Carolina	United States	28204
30	Research Site	Charlotte	North Carolina	United States	28210
31	Research Site	Raleigh	North Carolina	United States	27617
32	Research Site	Cleveland	Ohio	United States	44109
33	Research Site	Middleburg Heights	Ohio	United States	44130
34	Research Site	Oklahoma City	Oklahoma	United States	73101
35	Research Site	Tulsa	Oklahoma	United States	74104
36	Research Site	Philadelphia	Pennsylvania	United States	19140
37	Research Site	Pittsburgh	Pennsylvania	United States	15224
38	Research Site	Wyomissing	Pennsylvania	United States	19610
39	Research Site	Charleston	South Carolina	United States	29406
40	Research Site	Charleston	South Carolina	United States	29407
41	Research Site	Charleston	South Carolina	United States	29425
42	Research Site	Jackson	Tennessee	United States	38305
43	Research Site	Memphis	Tennessee	United States	38119
44	Research Site	Amarillo	Texas	United States	79124
45	Research Site	Austin	Texas	United States	78731
46	Research Site	Austin	Texas	United States	78745
47	Research Site	Dallas	Texas	United States	75231
48	Research Site	Houston	Texas	United States	77074
49	Research Site	Houston	Texas	United States	77099
50	Research Site	Mesquite	Texas	United States	75150
51	Research Site	San Antonio	Texas	United States	78232
52	Research Site	Glendale	Wisconsin	United States	53217
53	Research Site	Cordoba		Argentina	X5004AUL
54	Research Site	San Miguel de Tucuman		Argentina	T4000AXL
55	Research Site	Fitzroy		Australia	3065
56	Research Site	Kogarah		Australia	2217
57	Research Site	St Leonards		Australia	2065
58	Research Site	Belo Horizonte		Brazil	30150-221
59	Research Site	Juiz de Fora		Brazil	36010-570
60	Research Site	Porto Alegre		Brazil	90560-030
61	Research Site	Salvador		Brazil	40150-150
62	Research Site	Osorno		Chile	5311092
63	Research Site	Santiago		Chile	8320000
64	Research Site	Vina del Mar		Chile	2520997
65	Research Site	Armenia		Colombia	630004
66	Research Site	Barranquilla		Colombia	0
67	Research Site	Bogota		Colombia	110221
68	Research Site	Bogota		Colombia	111211
69	Research Site	Bucaramanga		Colombia	680003
70	Research Site	Medellin		Colombia	050021
71	Research Site	Berlin		Germany	10117
72	Research Site	Dessau-RoBlau		Germany	06847
73	Research Site	Frankfurt am Main		Germany	60528
74	Research Site	Göttingen		Germany	37075
75	Research Site	Kirchheim		Germany	73230
76	Research Site	Köln		Germany	50937
77	Research Site	Budapest		Hungary	1097
78	Research Site	Debrecen		Hungary	4032
79	Research Site	Szeged		Hungary	6725
80	Research Site	Zalaegerszeg		Hungary	8900
81	Research Site	Haifa		Israel	31048
82	Research Site	Haifa		Israel	3109601
83	Research Site	Jerusalem		Israel	9122001
84	Research Site	Kfar Saba		Israel	49281
85	Research Site	Petach-Tikva		Israel	49100
86	Research Site	Tel Aviv		Israel	64239
87	Research Site	Milano		Italy	20132
88	Research Site	Milano		Italy	20157
89	Research Site	Padova		Italy	35128
90	Research Site	Daejeon		Korea, Republic of	301-721
91	Research Site	Gwangju		Korea, Republic of	61469
92	Research Site	Jeonju-si		Korea, Republic of	54907
93	Research Site	Seoul		Korea, Republic of	03080
94	Research Site	Seoul		Korea, Republic of	150-713
95	Research Site	Suwon-si		Korea, Republic of	61469
96	Research Site	Hamilton		New Zealand	3204
97	Research Site	Wellington		New Zealand	6021
98	Research Site	Arequipa		Peru	54
99	Research Site	Lima		Peru	15023
100	Research Site	Lima		Peru	15033
101	Research Site	Lima		Peru	15046
102	Research Site	Lima		Peru	15073
103	Research Site	Lima		Peru	LIMA 01
104	Research Site	Lima		Peru	LIMA 31
105	Research Site	Białystok		Poland	15-297
106	Research Site	Bydgoszcz		Poland	85-168
107	Research Site	Elblag		Poland	82-300
108	Research Site	Kraków		Poland	31-011
109	Research Site	Lublin		Poland	20-582
110	Research Site	Nadarzyn		Poland	05-830
111	Research Site	Poznań		Poland	60-773
112	Research Site	Poznań		Poland	61-397
113	Research Site	Sosnowiec		Poland	41-200
114	Research Site	Starachowice		Poland	27-200
115	Research Site	Szczecin		Poland	71-252
116	Research Site	Ustron		Poland	43-450
117	Research Site	Warszawa		Poland	02-118
118	Research Site	Warszawa		Poland	50-088
119	Research Site	Brasov		Romania	500283
120	Research Site	Bucharest		Romania	011172
121	Research Site	Bucuresti		Romania	010584
122	Research Site	Bucuresti		Romania	011172
123	Research Site	Bucuresti		Romania	020475
124	Research Site	Cluj Napoca		Romania	400006
125	Research Site	Galati		Romania	800578
126	Research Site	Tg Mures		Romania	540136
127	Research Site	Kaohsiung Hsien		Taiwan	83342
128	Research Site	Taichung		Taiwan	404
129	Research Site	Taichung		Taiwan	40705
130	Research Site	Taipei		Taiwan	10002
131	Research Site	Kiev		Ukraine	03680
132	Research Site	Kyiv		Ukraine	01601
133	Research Site	Kyiv		Ukraine	02002
134	Research Site	Lviv		Ukraine	79010
135	Research Site	Lviv		Ukraine	79011
136	Research Site	Ternopil		Ukraine	46002
137	Research Site	Uzhgorod		Ukraine	88000
138	Research Site	Vinnytsia		Ukraine	21018
139	Research Site	Zaporizhzhia		Ukraine	69600
140	Research Site	Brighton		United Kingdom	BN2 5BE
141	Research Site	Doncaster		United Kingdom	DN2 5LT
142	Research Site	Leeds		United Kingdom	LS7 4SA
143	Research Site	London		United Kingdom	SE1 2PR
144	Research Site	Manchester		United Kingdom	M13 9WL
145	Research Site	Romford		United Kingdom	RM7 0AG
146	Research Site	Staffordshire		United Kingdom	WS11 5XY

Sponsors and Collaborators

• AstraZeneca
• PRA Health Sciences

Investigators

• Study Director: Herbert Hutman, MD, Medical Science Director

Study Documents (Full-Text)

• Study Protocol - May 18, 2016
• Statistical Analysis Plan - Aug 20, 2018

More Information

Additional Information:

• CSP redacted.
• SAP redacted.

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02446912
• Other Study ID Numbers: D3461C00005
• First Posted: May 18, 2015
• Last Update Posted: Dec 5, 2019
• Last Verified: Nov 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AstraZeneca: Active Systemic Lupus Erythematosus
• Additional relevant MeSH terms: Lupus Erythematosus, Systemic

Study Results

Participant Flow

Recruitment Details	Participants took part in the trial at 123 sites in 18 countries worldwide.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Period Title: Overall Study
STARTED	93	180	184
Participants Who Completed Week 52	80	153	157
COMPLETED	75	145	149
NOT COMPLETED	18	35	35

Baseline Characteristics

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo	Total
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Total of all reporting groups
Overall Participants	93	180	184	457
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	40.8 (12.05)	42.0 (11.99)	41.0 (12.30)	41.3 (12.11)
Age, Customized (Count of Participants)
< 18	0 0%	0 0%	0 0%	0 0%
≥ 18 to < 65	90 96.8%	169 93.9%	178 96.7%	437 95.6%
≥ 65	3 3.2%	11 6.1%	6 3.3%	20 4.4%
Sex: Female, Male (Count of Participants)
Female	86 92.5%	165 91.7%	171 92.9%	422 92.3%
Male	7 7.5%	15 8.3%	13 7.1%	35 7.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	20 21.5%	32 17.8%	35 19%	87 19%
Not Hispanic or Latino	73 78.5%	148 82.2%	149 81%	370 81%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 0.5%	1 0.2%
Asian	8 8.6%	11 6.1%	5 2.7%	24 5.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	14 15.1%	29 16.1%	23 12.5%	66 14.4%
White	64 68.8%	125 69.4%	137 74.5%	326 71.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	7 7.5%	15 8.3%	18 9.8%	40 8.8%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	164.02 (8.208)	162.99 (7.829)	163.10 (8.030)	163.24 (7.980)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	73.57 (19.469)	75.36 (20.343)	74.69 (19.332)	74.72 (19.731)
Body Mass Index (BMI) (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	27.31 (6.81)	28.25 (6.899)	28.09 (7.145)	28.00 (6.976)

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index ≥4 (SRI[4]) at Week 52 (Original Analysis With Restricted Medication Rules)
Description	SRI(4) was defined as meeting all of the following criteria: Reduction from baseline of ≥4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) No new organ systems affected, defined by 1 or more British Isles Lupus Assessment Group (BILAG-2004) A or 2 or more BILAG-2004 B items No worsening from baseline in participants lupus disease activity. Worsening was defined as an increase of ≥0.30 points on a 3-point Physician's Global Assessment (PGA) visual analogue scale (VAS) No discontinuation of investigational product and no use of restricted medications beyond the pre-specified analysis threshold.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set - all randomized participants who received at least one dose of investigational product.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	93	180	184
Count of Participants [Participants]	35 37.6%	65 36.1%	74 40.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anifrolumab 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	The difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors (SLEDAI-2K score at screening [<10 points vs >= 10 points], Week 0 OCS dose [<10 mg/day vs >=10 mg/day prednisone or equivalent] and type I IFN gene signature test result at screening [high vs low]).
Statistical Test of Hypothesis	p-Value	0.412
	Comments	Nominal p-value
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.2
	Confidence Interval	(2-Sided) 95%; -14.2 to 5.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Anifrolumab 150 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.6
	Confidence Interval	(2-Sided) 95%; -14.7 to 9.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Post-Hoc Outcome

Title	Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index ≥4 (SRI[4]) at Week 52 (Post-Hoc Analysis With Revised Restricted Medication Rules)
Description	SRI(4) was defined as meeting all of the following criteria: Reduction from baseline of ≥4 points in the SLEDAI-2K No new organ systems affected, defined by 1 or more BILAG-2004 A or 2 or more BILAG-2004 B items No worsening from baseline in lupus disease activity. Worsening defined as an increase of ≥0.30 points on a 3-point PGA VAS No discontinuation of investigational product and no use of restricted medications beyond the revised post-hoc allowed threshold. Revised rules were designed to be more clinically appropriate, capture intent of protocol, minimize the risk of restricted medications confounding efficacy, and to allow appropriate quantification and interpretation of the relevant endpoints.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set - all randomized participants who received at least one dose of investigational product.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	93	180	184
Count of Participants [Participants]	45 48.4%	84 46.7%	79 42.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anifrolumab 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	The difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors (SLEDAI-2K score at screening [<10 points vs >= 10 points], Week 0 OCS dose [<10 mg/day vs >=10 mg/day prednisone or equivalent] and type I IFN gene signature test result at screening [high vs low]).
Statistical Test of Hypothesis	p-Value	0.455
	Comments	Nominal p-value
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.9
	Confidence Interval	(2-Sided) 95%; -6.3 to 14.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Anifrolumab 150 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.5
	Confidence Interval	(2-Sided) 95%; -6.7 to 17.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index of ≥4 at Week 52 in the Interferon (IFN) Test-High Sub-Group (Original Analysis With Restricted Medication Rules)
Description	SRI(4) was defined as meeting all of the following criteria: Reduction from baseline of ≥4 points in the SLEDAI-2K No new organ systems affected, defined by 1 or more BILAG-2004 A or 2 or more BILAG-2004 B No worsening from baseline in participants lupus disease activity. Worsening was defined as an increase of ≥0.30 points on a 3-point PGA VAS No discontinuation of investigational product and no use of restricted medications beyond the pre-specified analysis threshold.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

All participants who received investigational product with non-missing baseline measurements, and high IFN test results.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	76	148	151
Count of Participants [Participants]	30 32.3%	53 29.4%	59 32.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anifrolumab 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	The difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors (SLEDAI-2K score at screening [<10 points vs >= 10 points], Week 0 OCS dose [<10 mg/day vs >=10 mg/day prednisone or equivalent] and type I IFN gene signature test result at screening [high vs low]).
Statistical Test of Hypothesis	p-Value	0.549
	Comments	Nominal p-value
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.4
	Confidence Interval	(2-Sided) 95%; -14.4 to 7.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Post-Hoc Outcome

Title	Number of Participants Who Achieved an Systemic Lupus Erythematosus (SLE) Responder Index of ≥4 at Week 52 in the Interferon (IFN) Test-High Sub-Group (Post-Hoc Analysis With Revised Restricted Medication Rules)
Description	SRI(4) was defined as meeting all of the following criteria: Reduction from baseline of ≥4 points in the SLEDAI-2K No new organ systems affected, defined by 1 or more BILAG-2004 A or 2 or more BILAG-2004 B items No worsening from baseline in lupus disease activity. Worsening defined as an increase of ≥0.30 points on a 3-point PGA VAS No discontinuation of investigational product and no use of restricted medications beyond the revised post-hoc analysis threshold. Revised rules were designed to be more clinically appropriate, capture intent of protocol, minimize the risk of restricted medications confounding efficacy, and to allow appropriate quantification and interpretation of the relevant endpoints.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

All participants who received investigational product with non-missing baseline measurements, and high IFN test results.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	76	148	151
Count of Participants [Participants]	40 43%	71 39.4%	63 34.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anifrolumab 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	The difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors (SLEDAI-2K score at screening [<10 points vs >= 10 points], Week 0 OCS dose [<10 mg/day vs >=10 mg/day prednisone or equivalent] and type I IFN gene signature test result at screening [high vs low]).
Statistical Test of Hypothesis	p-Value	0.261
	Comments	Nominal p-value
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.4
	Confidence Interval	(2-Sided) 95%; -4.8 to 17.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Participants Who Achieved and Maintained an Oral Corticosteroid (OCS) Dose of ≤7.5 mg/Day in the Sub-group of Participants With Baseline OCS ≥10 mg/Day (Original Analysis With Restricted Medication Rules)
Description	Maintained OCS reduction was defined by meeting all the following criteria: Achieve an OCS dose of ≤7.5 mg/day prednisone or equivalent by Week 40 Maintain an OCS dose ≤7.5 mg/day prednisone or equivalent from Week 40 to Week 52 No discontinuation of investigational product and no use of restricted medications beyond the pre-specified analysis threshold.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

All participants who received investigational product, who had a baseline OCS ≥10 mg/day, and had non-missing baseline measurements.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	48	103	102
Count of Participants [Participants]	17 18.3%	42 23.3%	33 17.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anifrolumab 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	The difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors (SLEDAI-2K score at screening [<10 points vs >= 10 points], Week 0 OCS dose [<10 mg/day vs >=10 mg/day prednisone or equivalent] and type I IFN gene signature test result at screening [high vs low]).
Statistical Test of Hypothesis	p-Value	0.180
	Comments	Nominal p-value
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	8.9
	Confidence Interval	(2-Sided) 95%; -4.1 to 21.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Post-Hoc Outcome

Title	Number of Participants Who Achieved and Maintained an Oral Corticosteroid (OCS) Dose of ≤7.5 mg/Day in the Sub-group of Participants With Baseline OCS ≥10 mg/Day (Post-Hoc Analysis With Revised Restricted Medication Rules)
Description	Maintained OCS reduction was defined by meeting all of the following criteria: Achieve an OCS dose of ≤7.5 mg/day prednisone or equivalent by Week 40 Maintain an OCS dose ≤7.5 mg/day prednisone or equivalent from Week 40 to Week 52 No discontinuation of investigational product and no use of restricted medications beyond the revised post-hoc analysis threshold. Revised rules were designed to be more clinically appropriate, capture intent of protocol, minimize the risk of restricted medication confounding efficacy, and to allow appropriate quantification and interpretation of the relevant endpoints.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

All participants who received investigational product, who had a baseline OCS ≥10 mg/day, and had non-missing baseline measurements.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	48	103	102
Count of Participants [Participants]	24 25.8%	50 27.8%	33 17.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anifrolumab 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	The difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors (SLEDAI-2K score at screening [<10 points vs >= 10 points], Week 0 OCS dose [<10 mg/day vs >=10 mg/day prednisone or equivalent] and type I IFN gene signature test result at screening [high vs low]).
Statistical Test of Hypothesis	p-Value	0.013
	Comments	Nominal p-value
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	16.7
	Confidence Interval	(2-Sided) 95%; 3.5 to 29.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Number of Participants With a ≥50% Reduction in CLASI Activity Score at Week 12 in the Sub-group of Participants With Baseline CLASI Activity Score ≥10 (Original Analysis With Restricted Medication Rules)
Description	50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score compared to baseline was defined by meeting all of the following criteria: Achieve ≥50% reduction of CLASI activity score at Week 12 compared to baseline No discontinuation of investigational product and no use of restricted medications beyond the pre-specified analysis threshold before assessment.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

All participants who received investigational product, had a baseline CLASI Activity Score ≥10, and had non-missing baseline measurements.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	30	58	54
Count of Participants [Participants]	15 16.1%	24 13.3%	14 7.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anifrolumab 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	The difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors (SLEDAI-2K score at screening [<10 points vs >= 10 points], Week 0 OCS dose [<10 mg/day vs >=10 mg/day prednisone or equivalent] and type I IFN gene signature test result at screening [high vs low]).
Statistical Test of Hypothesis	p-Value	0.054
	Comments	Nominal p-value
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	17.0
	Confidence Interval	(2-Sided) 95%; -0.3 to 34.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Post-Hoc Outcome

Title	Number of Participants With a ≥50% Reduction in CLASI Activity Score at Week 12 in the Sub-group of Participants With Baseline CLASI Activity Score ≥10 (Post-Hoc Analysis With Revised Restricted Medication Rules)
Description	50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score compared to baseline was defined by meeting all the following criteria: Achieve ≥50% reduction of CLASI activity score at Week 12 compared to baseline No discontinuation of investigational product and no use of restricted medications beyond the revised post-hoc analysis threshold before assessment. Revised rules were designed to be more clinically appropriate, capture intent of protocol, minimize the risk of restricted medication confounding efficacy, and to allow appropriate quantification and interpretation of the relevant endpoints.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

All participants who received investigational product, had a baseline CLASI Activity Score ≥10, and had non-missing baseline measurements.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	30	58	54
Count of Participants [Participants]	16 17.2%	25 13.9%	14 7.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anifrolumab 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	The difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors (SLEDAI-2K score at screening [<10 points vs >= 10 points], Week 0 OCS dose [<10 mg/day vs >=10 mg/day prednisone or equivalent] and type I IFN gene signature test result at screening [high vs low]).
Statistical Test of Hypothesis	p-Value	0.034
	Comments	Nominal p-value
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	18.7
	Confidence Interval	(2-Sided) 95%; 1.4 to 36.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index of ≥4 (SRI[4]) at Week 24 (Original Analysis With Restricted Medication Rules)
Description	SRI(4) was defined as meeting all of the following criteria: Reduction from baseline of ≥4 points in the SLEDAI-2K No new organ systems affected as defined by 1 or more BILAG-2004 A or 2 or more BILAG-2004 B items No worsening from baseline in participants lupus disease activity. Worsening was defined as an increase of ≥0.30 points on a 3-point PGA VAS No discontinuation of investigational product and no use of restricted medications beyond the pre-specified threshold.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Full analysis set - all randomized participants who received at least one dose of investigational product.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	93	180	184
Count of Participants [Participants]	34 36.6%	74 41.1%	75 40.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anifrolumab 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	The difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors (SLEDAI-2K score at screening [<10 points vs >= 10 points], Week 0 OCS dose [<10 mg/day vs >=10 mg/day prednisone or equivalent] and type I IFN gene signature test result at screening [high vs low]).
Statistical Test of Hypothesis	p-Value	0.905
	Comments	Nominal p-value
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -9.4 to 10.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Post-Hoc Outcome

Title	Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index of ≥4 (SRI[4]) at Week 24 (Post-Hoc Analysis With Revised Restricted Medication Rules)
Description	SRI(4) was defined as meeting all of the following criteria: Reduction from baseline of ≥4 points in the SLEDAI-2K No new organ systems affected, defined by 1 or more BILAG-2004 A or 2 or more BILAG-2004 B items No worsening from baseline in lupus disease activity. Worsening defined as an increase of ≥0.30 points on a 3-point PGA VAS No discontinuation of investigational product and no use of restricted medications beyond the revised post-hoc allowed threshold. Revised rules were designed to be more clinically appropriate, capture intent of protocol, minimize the risk of restricted medications confounding efficacy, and to allow appropriate quantification and interpretation of the relevant endpoints.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Full analysis set - all randomized participants who received at least one dose of investigational product.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	93	180	184
Count of Participants [Participants]	40 43%	83 46.1%	79 42.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anifrolumab 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	The difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors (SLEDAI-2K score at screening [<10 points vs >= 10 points], Week 0 OCS dose [<10 mg/day vs >=10 mg/day prednisone or equivalent] and type I IFN gene signature test result at screening [high vs low]).
Statistical Test of Hypothesis	p-Value	0.515
	Comments	Nominal p-value
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.3
	Confidence Interval	(2-Sided) 95%; -6.7 to 13.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Annualized Flare Rate
Description	A flare was defined as either 1 or more new British Isle Lupus Assessment Group (BILAG-2004) A or 2 or more new BILAG-2004 B items compared to the previous visit. The occurrence of a new flare was checked for each available visit versus the previous available visit up to Week 52. If no new flares occurred, the number of flares was set to 0. Otherwise all flares were counted leading to the maximum number of flares of 13. The annualized flare rate was calculated as the number of flares divided by the flare exposure time in days multiplied with 365.25 (1 year). The flare exposure time is the time up to Week 52 (date of BILAG-2004 assessment at Week 52) or up to the date of last available BILAG-2004 assessment.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set - all randomized participants who received investigational product with non-missing baseline measurements.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	93	180	184
Number [Annualized flare rate ratio]	0.62	0.60	0.72

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anifrolumab 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	Analysed using a negative binomial regression model. The response variable in the model is the number of flares over the 52-week treatment period. The model includes covariates of treatment group, and the stratification factors (SLEDAI-2K score at screening [<10 points vs >=10 points], Week 0 OCS dose [<10 mg/day vs >=10 mg/day prednisone or equivalent] and type I IFN gene signature test result at screening [high vs low]). The logarithm of the follow-up time is used as an offset variable.
Statistical Test of Hypothesis	p-Value	0.258
	Comments	Nominal p-value
	Method	Negative binomial regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.60 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Number of Participants Who Met the Criteria for British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response (Original Analysis With Restricted Medication Rules)
Description	A BICLA responder was achieved if all of the following criteria was met: All criteria related to SRI(4) (please see primary endpoint) plus: Reduction of all baseline BILAG-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by 1 or more BILAG-2004 A or 1 or more new BILAG-2004 B item No discontinuation of investigational product and no use of restricted medications beyond the revised post-hoc analysis threshold before assessment.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set - all randomized participants who received at least one dose of investigational product.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	93	180	184
Count of Participants [Participants]	27 29%	67 37.2%	49 26.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anifrolumab 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	The difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors (SLEDAI-2K score at screening [<10 points vs >= 10 points], Week 0 OCS dose [<10 mg/day vs >=10 mg/day prednisone or equivalent] and type I IFN gene signature test result at screening [high vs low]).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	10.1
	Confidence Interval	(2-Sided) 95%; 0.6 to 19.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Post-Hoc Outcome

Title	Number of Participants Who Met the Criteria for British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response (Post-Hoc Analysis With Revised Restricted Medication Rules)
Description	A BICLA responder was achieved if all of the following criteria was met: All criteria related to SRI(4) (please see primary endpoint) plus: Reduction of all baseline BILAG-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by 1 or more BILAG-2004 A or 1 or more new BILAG-2004 B item No discontinuation of investigational product and no use of restricted medications beyond the revised post-hoc analysis threshold before assessment. Revised rules were designed to be more clinically appropriate, capture intent of protocol, minimize the risk of restricted medications confounding efficacy, and to allow appropriate quantification and interpretation of the relevant endpoints.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set - all randomized participants who received at least one dose of investigation product.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	93	180	184
Count of Participants [Participants]	35 37.6%	83 46.1%	54 29.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anifrolumab 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	The difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors (SLEDAI-2K score at screening [<10 points vs >= 10 points], Week 0 OCS dose [<10 mg/day vs >=10 mg/day prednisone or equivalent] and type I IFN gene signature test result at screening [high vs low]).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	16.4
	Confidence Interval	(2-Sided) 95%; 6.7 to 26.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Number of Participants Reporting One or More Adverse Events (AE)
Description	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. AEs were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose [Week 48]), or until Week 52 for participants who enrolled onto the long term extension (LTE). The reported value is inclusive of serious and non-serious AEs.
Time Frame	Baseline to End of Trial (Maximum of 60 weeks)

Outcome Measure Data

Analysis Population Description

Full analysis set - all randomized participants who received at least one dose of investigational product.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	93	180	184
Count of Participants [Participants]	80 86%	161 89.4%	145 78.8%

15. Secondary Outcome

Title	Number of Participants Reporting One or More Adverse Events of Special Interest (AESI)
Description	An AESI is an AE of scientific and medical concern specific to understanding biologics and requires close monitoring and rapid communication by the Investigator to the Sponsor/Sponsor's delegate. An AESI may be serious or nonserious. The events of interest 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, MI, or cardiovascular death). AEs were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose [Week 48]), or until Week 52 for participants who enrolled onto the long term extension (LTE).
Time Frame	Baseline to End of Trial (Maximum of 60 weeks)

Outcome Measure Data

Analysis Population Description

Full analysis set - all randomized participants who received at least one dose of investigational product.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	93	180	184
Count of Participants [Participants]	11 11.8%	23 12.8%	18 9.8%

16. Secondary Outcome

Title	Number of Participants With Markedly Abnormal Vital Signs
Description	Vital signs included oral temperature, blood pressure (BP), pulse rate, and respiratory rate. Vital signs were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose [Week 48]), or until Week 52 for participants who enrolled onto the long term extension (LTE).
Time Frame	Baseline to End of Trial (Maximum of 60 weeks)

Outcome Measure Data

Analysis Population Description

Full analysis set - all randomized participants who received at least one dose of investigational product.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	93	180	184
Count of Participants [Participants]	14 15.1%	36 20%	46 25%

17. Secondary Outcome

Title	Number of Participants With Markedly Abnormal Physical Examinations
Description	Physical examinations included height and weight. Participants were weighed at each study visit and any medically significant changes were reported. Physical examination values were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose [Week 48]), or until Week 52 for participants who enrolled onto the long term extension (LTE).
Time Frame	Baseline to End of Trial (Maximum of 60 weeks)

Outcome Measure Data

Analysis Population Description

Full analysis set - all randomized participants who received at least one dose of investigational product.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	93	180	184
Count of Participants [Participants]	3 3.2%	2 1.1%	2 1.1%

18. Secondary Outcome

Title	Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Scores
Description	ECGs documented the date, time, heart rate, QRS duration, PR interval, RR interval, QT, and corrected QT interval, which were calculated using the Fridericia formula. The investigator judged the overall interpretation as normal or abnormal, and if abnormal it was decided as to whether or not the abnormality was clinically significant or not clinically significant.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set - all randomized participants who received at least one dose of investigational product.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	93	180	184
Count of Participants [Participants]	0 0%	0 0%	0 0%

19. Secondary Outcome

Title	Number of Participants With Mild To Moderate Lupus Flare Evaluated by Modified Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI Flare Index
Description	The modified SELENA flare index was completed by the Investigator or delegated/qualified physician. Assessment of flares were scored in comparison to the participant's previous visit and should only include findings which, in the opinion of the Investigator, are due to systemic lupus erythematosus (SLE) disease activity within that timeframe. Flare was defined as any 1 criterion present in either the Mild/Moderate Flare or Severe Flare categories. Number of flares were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose [Week 48]), or until Week 52 for participants who enrolled onto the long term extension (LTE).
Time Frame	Baseline to End of Trial (Maximum of 60 weeks)

Outcome Measure Data

Analysis Population Description

Full analysis set - all randomized participants who received at least one dose of investigational product.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	93	180	184
Count of Participants [Participants]	38 40.9%	58 32.2%	67 36.4%

20. Secondary Outcome

Title	Number of Participants With Markedly Abnormal Laboratory Tests
Description	Laboratory tests were collected at central clinical laboratories and included hematology, serum chemistry and urinalysis tests. Laboratory values were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose [Week 48]), or until Week 52 for participants who enrolled onto the long term extension (LTE).
Time Frame	Baseline to End of Trial (Maximum of 60 weeks)

Outcome Measure Data

Analysis Population Description

Full analysis set - all randomized participants who received at least one dose of investigational product.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	93	180	184
Count of Participants [Participants]	44 47.3%	71 39.4%	87 47.3%

21. Secondary Outcome

Title	Number of Participants With Suicidal Ideation or Behaviour Assessed Via the Columbia Suicide Severity Rating Scale (C-SSRS)
Description	The C-SSRS is an assessment tool that evaluates suicidal ideation and behavior. Number of participants with suicidal ideation or behavior was defined as the number of participants who answered "yes" at any time during the treatment period (Baseline to Week 52) to one of the 10 categories: Category 1: Wish to be dead Category 2: Non-specific active suicidal thoughts Category 3: Active suicidal ideation with any methods (not plan) without intent to act Category 4: Active suicidal ideation with some intent to act, without specific plan Category 5: Active suicidal ideation with specific plan and intent Category 6: Preparatory acts or behavior Category 7: Aborted attempt Category 8: Interrupted attempt Category 9: Actual attempt (non-fatal) Category 10: Completed suicide
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set - all randomized participants who received at least one dose of investigational product.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	93	180	184
Suicidal ideation	1 1.1%	2 1.1%	2 1.1%
Suicidal behaviour	0 0%	0 0%	1 0.5%

22. Secondary Outcome

Title	Change From Baseline in Personal Health Questionnaire Depression Scale-8 (PHQ-8) Score
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. A negative change from baseline score indicates improvement in symptoms.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

All participants who received study drug with non-missing baseline and week 52 measurements.

Arm/Group Title	Anifrolumab 150 mg	Anifrolumab 300 mg	Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Measure Participants	71	130	138
Mean (Standard Deviation) [Score on a Scale]	-2.1 (4.43)	-2.7 (5.58)	-1.7 (5.40)

Adverse Events

Time Frame	Baseline to End of Trial (Maximum of 60 weeks post first dose)
Adverse Event Reporting Description	AEs were either spontaneously reported by the participant or reported in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. Full analysis set: All participants who had received at least one dose of investigational product.
Arm/Group Title	Anifrolumab 150 mg		Anifrolumab 300 mg		Placebo
Arm/Group Description	Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)		Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)		Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
All Cause Mortality
	Anifrolumab 150 mg		Anifrolumab 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/93 (0%)		1/180 (0.6%)		1/184 (0.5%)
Serious Adverse Events
	Anifrolumab 150 mg		Anifrolumab 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/93 (10.8%)		27/180 (15%)		35/184 (19%)
Blood and lymphatic system disorders
Neutropenia	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Anaemia	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Cardiac disorders
Acute coronary syndrome	1/93 (1.1%)	1	0/180 (0%)	0	0/184 (0%)	0
Angina unstable	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Coronary artery disease	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Myocardial infarction	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Atrial fibrillation	0/93 (0%)	0	0/180 (0%)	0	2/184 (1.1%)	2
Cardiac failure	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Pericarditis	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Supraventricular tachycardia	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Ventricular arrhythmia	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Eye disorders
Ulcerative keratitis	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Gastrointestinal disorders
Colitis	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Gastrooesophageal reflux disease	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Haemorrhoidal haemorrhage	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Small intestinal obstruction	1/93 (1.1%)	1	0/180 (0%)	0	0/184 (0%)	0
General disorders
Chest pain	0/93 (0%)	0	2/180 (1.1%)	2	0/184 (0%)	0
Non-cardiac chest pain	0/93 (0%)	0	1/180 (0.6%)	1	1/184 (0.5%)	1
Pain	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Pyrexia	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Immune system disorders
Anaphylactic reaction	1/93 (1.1%)	1	0/180 (0%)	0	0/184 (0%)	0
Food allergy	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Infections and infestations
Pneumonia	1/93 (1.1%)	1	3/180 (1.7%)	3	1/184 (0.5%)	1
Urinary tract infection	1/93 (1.1%)	2	1/180 (0.6%)	1	2/184 (1.1%)	2
Appenicitis	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Bronchitis	0/93 (0%)	0	1/180 (0.6%)	1	1/184 (0.5%)	1
Cellulitis	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Gangrene	1/93 (1.1%)	1	0/180 (0%)	0	0/184 (0%)	0
Gastroenteritis	0/93 (0%)	0	1/180 (0.6%)	1	1/184 (0.5%)	1
Genital herpes	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Meningitis viral	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Pyelonephritis acute	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Sepsis	1/93 (1.1%)	1	0/180 (0%)	0	1/184 (0.5%)	1
Subcutaneous abscess	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Encephalitis	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Epididymitis	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Infectious colitis	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Klebsiella infection	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Meningitis	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Otitis media chronic	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Pelvic infection	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Postoperative wound infection	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Septic shock	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	2
Sinusitis	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Staphylococcal bacteraemia	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Injury, poisoning and procedural complications
Facial bones fracture	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Post procedural complication	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Thoracic vertebral fracture	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Perirenal haematoma	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Post procedural haematoma	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Rib fracture	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Investigations
Weight decreased	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Metabolism and nutrition disorders
Hypercalcaemia	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus	2/93 (2.2%)	3	4/180 (2.2%)	6	5/184 (2.7%)	6
Fracture pain	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Musculoskeletal chest pain	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Invasive breast carcinoma	1/93 (1.1%)	1	0/180 (0%)	0	0/184 (0%)	0
Invasive ductal breast carcinoma	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Haemangioma of liver	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Nervous system disorders
Myasthenia gravis	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Seizure	1/93 (1.1%)	1	0/180 (0%)	0	0/184 (0%)	0
Syncope	0/93 (0%)	0	1/180 (0.6%)	1	1/184 (0.5%)	1
Neuropsychiatric lupus	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Psychiatric disorders
Conversion disorder	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Suicide attempt	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Renal and urinary disorders
Nephritis	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Chronic kidney disease	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Dysuria	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Lupus nephritis	0/93 (0%)	0	0/180 (0%)	0	2/184 (1.1%)	2
Renal failure	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Reproductive system and breast disorders
Endometrial hypertrophy	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	0/93 (0%)	0	2/180 (1.1%)	2	1/184 (0.5%)	1
Acute respiratory failure	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Dyspnoea	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Pulmonary embolism	0/93 (0%)	0	1/180 (0.6%)	1	1/184 (0.5%)	1
Pleurisy	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Respiratory failure	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Skin and subcutaneous tissue disorders
Angioedema	0/93 (0%)	0	1/180 (0.6%)	1	0/184 (0%)	0
Drug eruption	1/93 (1.1%)	1	0/180 (0%)	0	0/184 (0%)	0
Swelling face	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Urticaria	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Vascular disorders
Raynaud's phenomenon	1/93 (1.1%)	1	0/180 (0%)	0	0/184 (0%)	0
Deep vein thrombosis	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Hypertension	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Venous thrombosis limb	0/93 (0%)	0	0/180 (0%)	0	1/184 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Anifrolumab 150 mg		Anifrolumab 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	78/93 (83.9%)		157/180 (87.2%)		141/184 (76.6%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/93 (1.1%)	1	4/180 (2.2%)	4	3/184 (1.6%)	3
Anaemia	0/93 (0%)	0	1/180 (0.6%)	1	4/184 (2.2%)	4
Ear and labyrinth disorders
Ear pain	2/93 (2.2%)	2	2/180 (1.1%)	2	1/184 (0.5%)	1
Endocrine disorders
Steroid withdrawal syndrome	0/93 (0%)	0	5/180 (2.8%)	5	1/184 (0.5%)	1
Gastrointestinal disorders
Diarrhoea	8/93 (8.6%)	11	6/180 (3.3%)	9	14/184 (7.6%)	14
Vomiting	4/93 (4.3%)	7	9/180 (5%)	9	4/184 (2.2%)	6
Nausea	3/93 (3.2%)	5	9/180 (5%)	10	14/184 (7.6%)	19
Gastrooesophageal reflux disease	4/93 (4.3%)	4	5/180 (2.8%)	5	6/184 (3.3%)	6
Dyspepsia	6/93 (6.5%)	6	3/180 (1.7%)	6	5/184 (2.7%)	5
Abdominal pain	2/93 (2.2%)	2	4/180 (2.2%)	6	2/184 (1.1%)	2
Abdominal pain upper	1/93 (1.1%)	1	4/180 (2.2%)	5	8/184 (4.3%)	11
Constipation	1/93 (1.1%)	1	4/180 (2.2%)	4	2/184 (1.1%)	2
Abdominal distension	2/93 (2.2%)	2	0/180 (0%)	0	0/184 (0%)	0
Gastritis	1/93 (1.1%)	1	1/180 (0.6%)	1	5/184 (2.7%)	5
General disorders
Pyrexia	4/93 (4.3%)	5	5/180 (2.8%)	8	4/184 (2.2%)	5
Chest pain	1/93 (1.1%)	1	3/180 (1.7%)	3	0/184 (0%)	0
Non-cardiac chest pain	3/93 (3.2%)	3	1/180 (0.6%)	1	5/184 (2.7%)	6
Fatigue	0/93 (0%)	0	4/180 (2.2%)	5	2/184 (1.1%)	2
Oedema peripheral	2/93 (2.2%)	2	2/180 (1.1%)	2	3/184 (1.6%)	3
Peripheral swelling	2/93 (2.2%)	2	1/180 (0.6%)	1	1/184 (0.5%)	1
Immune system disorders
Hypersensitivity	4/93 (4.3%)	6	11/180 (6.1%)	12	2/184 (1.1%)	2
Infections and infestations
Nasopharyngitis	15/93 (16.1%)	18	36/180 (20%)	58	24/184 (13%)	28
Upper respiratory tract infection	17/93 (18.3%)	25	22/180 (12.2%)	27	19/184 (10.3%)	27
Urinary tract infection	8/93 (8.6%)	10	22/180 (12.2%)	29	26/184 (14.1%)	32
Bronchitis	7/93 (7.5%)	9	15/180 (8.3%)	17	9/184 (4.9%)	11
Pharyngitis	6/93 (6.5%)	8	12/180 (6.7%)	13	13/184 (7.1%)	15
Herpes zoster	5/93 (5.4%)	5	10/180 (5.6%)	10	3/184 (1.6%)	3
Sinusitis	5/93 (5.4%)	6	8/180 (4.4%)	12	12/184 (6.5%)	13
Pneumonia	4/93 (4.3%)	5	4/180 (2.2%)	4	2/184 (1.1%)	2
Gastroenteritis	5/93 (5.4%)	5	5/180 (2.8%)	5	2/184 (1.1%)	3
Oral herpes	0/93 (0%)	0	8/180 (4.4%)	10	5/184 (2.7%)	8
Cellulitis	0/93 (0%)	0	6/180 (3.3%)	6	2/184 (1.1%)	2
Folliculitis	4/93 (4.3%)	5	3/180 (1.7%)	4	3/184 (1.6%)	3
Conjunctivitis	2/93 (2.2%)	2	4/180 (2.2%)	5	1/184 (0.5%)	1
Influenza	2/93 (2.2%)	2	3/180 (1.7%)	3	2/184 (1.1%)	2
Respiratory tract infection	0/93 (0%)	0	5/180 (2.8%)	7	3/184 (1.6%)	3
Rhinitis	1/93 (1.1%)	1	4/180 (2.2%)	9	4/184 (2.2%)	4
Tooth infection	0/93 (0%)	0	5/180 (2.8%)	5	0/184 (0%)	0
Vulvovaginal mycotic infection	2/93 (2.2%)	2	3/180 (1.7%)	3	4/184 (2.2%)	4
Onychomycosis	0/93 (0%)	0	4/180 (2.2%)	4	0/184 (0%)	0
Subcutaneous abscess	2/93 (2.2%)	2	1/180 (0.6%)	1	1/184 (0.5%)	1
Furuncle	2/93 (2.2%)	3	1/180 (0.6%)	1	1/184 (0.5%)	1
Viral infection	2/93 (2.2%)	2	1/180 (0.6%)	1	2/184 (1.1%)	4
Cystitis	1/93 (1.1%)	1	1/180 (0.6%)	1	4/184 (2.2%)	4
Hordeolum	2/93 (2.2%)	2	0/180 (0%)	0	0/184 (0%)	0
Injury, poisoning and procedural complications
Infusion related reaction	9/93 (9.7%)	17	16/180 (8.9%)	37	13/184 (7.1%)	32
Contusion	2/93 (2.2%)	2	4/180 (2.2%)	4	3/184 (1.6%)	3
Fall	0/93 (0%)	0	6/180 (3.3%)	7	4/184 (2.2%)	4
Arthropod bite	0/93 (0%)	0	4/180 (2.2%)	4	3/184 (1.6%)	3
Rib fracture	2/93 (2.2%)	2	1/180 (0.6%)	1	1/184 (0.5%)	1
Investigations
Blood pressure increased	2/93 (2.2%)	2	2/180 (1.1%)	3	0/184 (0%)	0
Metabolism and nutrition disorders
Hypokalaemia	3/93 (3.2%)	4	1/180 (0.6%)	1	4/184 (2.2%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	2/93 (2.2%)	3	11/180 (6.1%)	13	3/184 (1.6%)	5
Back pain	2/93 (2.2%)	2	10/180 (5.6%)	10	13/184 (7.1%)	16
Fibromyalgia	3/93 (3.2%)	3	2/180 (1.1%)	2	4/184 (2.2%)	4
Pain in extremity	3/93 (3.2%)	3	2/180 (1.1%)	2	1/184 (0.5%)	1
Myalgia	2/93 (2.2%)	3	2/180 (1.1%)	2	5/184 (2.7%)	6
Osteoarthritis	3/93 (3.2%)	4	1/180 (0.6%)	1	1/184 (0.5%)	1
Trigger finger	2/93 (2.2%)	2	0/180 (0%)	0	0/184 (0%)	0
Bursitis	1/93 (1.1%)	1	0/180 (0%)	0	4/184 (2.2%)	5
Muscle spasms	1/93 (1.1%)	1	1/180 (0.6%)	1	4/184 (2.2%)	4
Osteoporosis	1/93 (1.1%)	1	0/180 (0%)	0	4/184 (2.2%)	4
Nervous system disorders
Headache	6/93 (6.5%)	8	17/180 (9.4%)	37	18/184 (9.8%)	23
Migraine	4/93 (4.3%)	4	5/180 (2.8%)	6	5/184 (2.7%)	6
Dizziness	2/93 (2.2%)	2	5/180 (2.8%)	5	7/184 (3.8%)	8
Psychiatric disorders
Depression	7/93 (7.5%)	7	6/180 (3.3%)	8	5/184 (2.7%)	5
Anxiety	4/93 (4.3%)	4	4/180 (2.2%)	5	4/184 (2.2%)	5
Insomnia	3/93 (3.2%)	3	4/180 (2.2%)	4	8/184 (4.3%)	9
Renal and urinary disorders
Renal colic	0/93 (0%)	0	4/180 (2.2%)	5	0/184 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	2/93 (2.2%)	2	11/180 (6.1%)	13	7/184 (3.8%)	9
Epistaxis	0/93 (0%)	0	1/180 (0.6%)	1	5/184 (2.7%)	7
Skin and subcutaneous tissue disorders
Rash pruritic	3/93 (3.2%)	3	0/180 (0%)	0	1/184 (0.5%)	1
Rash	1/93 (1.1%)	1	0/180 (0%)	0	5/184 (2.7%)	5
Vascular disorders
Hypertension	5/93 (5.4%)	5	4/180 (2.2%)	4	9/184 (4.9%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.