Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Sifalimumab in Adults With Systemic Lupus Erythematosus (NCT NCT01283139)

Last Updated: 2018-04-19

Results Overview

SRI (4) responder is defined as: 1) a reduction in baseline Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) disease activity score of greater than or equal to (\>=) 4 points (with increased deoxyribonucleic acid \[DNA\] binding item of SLEDAI-2K score based on the ANA Multi-Lyte® ANA-II Plus Test System); 2) no worsening in Physician Global Assessment (MDGA) (worsening is defined as an increase of \>=0.3 from baseline on a 0-3 visual analogue scale) and 3) no worsening in British Isles Lupus Assessment Group (BILAG-2004) (worsening is defined as at least 1 new 'A' score or 2 new 'B' scores on the BILAG-2004 compared with baseline).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

834 participants

Primary outcome timeframe

Day 365

Results posted on

2018-04-19

Participant Flow

A total of 834 participants were screened out of which 402 participants did not meet eligibility criteria and were considered screen failures, and 432 participants were randomized into the study.

Participant milestones

Participant milestones
Measure	Placebo Placebo matching to sifalimumab administered by intravenous infusion at a fixed dose of every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 200 Milligram (mg) Sifalimumab 200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 600 mg Sifalimumab 600 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 1,200 mg Sifalimumab 1,200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.
Overall Study STARTED	108	108	109	107
Overall Study COMPLETED	91	90	91	92
Overall Study NOT COMPLETED	17	18	18	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo matching to sifalimumab administered by intravenous infusion at a fixed dose of every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 200 Milligram (mg) Sifalimumab 200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 600 mg Sifalimumab 600 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 1,200 mg Sifalimumab 1,200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.
Overall Study Lost to Follow-up	5	2	3	1
Overall Study Withdrawal by Subject	8	8	6	8
Overall Study Death	2	0	2	2
Overall Study Lack of Efficacy	1	2	2	1
Overall Study Early termination due to AE/SAE	1	1	0	0
Overall Study Participant's refusal to continue	0	3	1	1
Overall Study Pregnancy	0	1	1	0
Overall Study Missed follow-up visit	0	1	2	2
Overall Study Participant randomized in error	0	0	1	0

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Sifalimumab in Adults With Systemic Lupus Erythematosus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=108 Participants Placebo matching to sifalimumab administered by intravenous infusion at a fixed dose of every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 200 Milligram (mg) n=108 Participants Sifalimumab 200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 600 mg n=109 Participants Sifalimumab 600 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 1,200 mg n=107 Participants Sifalimumab 1,200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Total n=432 Participants Total of all reporting groups
Age, Continuous	38.4 years STANDARD_DEVIATION 12.3 • n=5 Participants	39.9 years STANDARD_DEVIATION 11.4 • n=7 Participants	40.1 years STANDARD_DEVIATION 11.3 • n=5 Participants	39.4 years STANDARD_DEVIATION 12.1 • n=4 Participants	39.4 years STANDARD_DEVIATION 11.7 • n=21 Participants
Sex: Female, Male Female	101 Participants n=5 Participants	103 Participants n=7 Participants	98 Participants n=5 Participants	97 Participants n=4 Participants	399 Participants n=21 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants	10 Participants n=4 Participants	33 Participants n=21 Participants

PRIMARY outcome

Timeframe: Day 365

Population: The modified intent-to-treat (mITT) population included all randomized participants who received any investigational product and had a baseline primary efficacy measurement.

Outcome measures

Outcome measures
Measure	Placebo n=108 Participants Placebo matching to sifalimumab administered by intravenous infusion at a fixed dose of every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 200 Milligram (mg) n=108 Participants Sifalimumab 200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 600 mg n=108 Participants Sifalimumab 600 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 1,200 mg n=107 Participants Sifalimumab 1,200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.
Percentage of Participants Achieving a Response in Systemic Lupus Erythematosus Responder Index 4 (SRI [4])	45.4 percentage of participants	58.3 percentage of participants	56.5 percentage of participants	59.8 percentage of participants

PRIMARY outcome

Timeframe: Day 365

Population: The mITT population included all randomized participants who received any investigational product and had a baseline primary efficacy measurement. Here, "N" signifies number of participants with positive diagnostic test.

SRI (4) responder is defined as: 1) a reduction in baseline SLEDAI-2K disease activity score of \>=4 points (with increased DNA binding item of SLEDAI-2K score based on the ANA Multi-Lyte® ANA-II Plus Test System); 2) no worsening in Physician Global Assessment (MDGA) (worsening is defined as an increase of \>=0.3 from baseline on a 0-3 visual analogue scale) and 3) no worsening in BILAG-2004 (worsening is defined as at least 1 new 'A' score or 2 new 'B' scores on the BILAG-2004 compared with baseline).

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants Placebo matching to sifalimumab administered by intravenous infusion at a fixed dose of every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 200 Milligram (mg) n=87 Participants Sifalimumab 200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 600 mg n=88 Participants Sifalimumab 600 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 1,200 mg n=87 Participants Sifalimumab 1,200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.
Percentage of Participants Achieving a Positive Response in SRI (4) in 4-Gene Interferon Test High Participants	42.0 percentage of participants	57.5 percentage of participants	50.0 percentage of participants	57.5 percentage of participants

SECONDARY outcome

Timeframe: Day 365

Percentage of participants on \>=10 mg/day oral corticosteroids (OCS) at baseline who were able to taper it to \<=7.5 mg/day by Day 365 were recorded.

Outcome measures

Outcome measures
Measure	Placebo n=62 Participants Placebo matching to sifalimumab administered by intravenous infusion at a fixed dose of every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 200 Milligram (mg) n=61 Participants Sifalimumab 200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 600 mg n=53 Participants Sifalimumab 600 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 1,200 mg n=65 Participants Sifalimumab 1,200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.
Percentage of Participants on Greater Than or Equal to 10 mg/Day Oral Prednisone (or Equivalent) at Baseline Who Were Able to Reduce to Less Than or Equal to (<=) 7.5 mg/Day Reduce OCS to <=7.5 mg/day: Yes	6.5 percentage of participants	8.2 percentage of participants	9.4 percentage of participants	6.2 percentage of participants
Percentage of Participants on Greater Than or Equal to 10 mg/Day Oral Prednisone (or Equivalent) at Baseline Who Were Able to Reduce to Less Than or Equal to (<=) 7.5 mg/Day Reduce OCS to <=7.5 mg/day: No	93.5 percentage of participants	91.8 percentage of participants	90.6 percentage of participants	93.8 percentage of participants

SECONDARY outcome

Timeframe: Day 365

The CLASI consists of two scores, the first summarizes the activity of the disease while the second is a measure of the damage done by the disease. Activity is scored on the basis of erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. Damage is scored in terms of dyspigmentation and scarring, including scarring alopecia. The percentage of participants with a CLASI activity score \>=10 at baseline who achieved a clinically significant (\>=4-point) reduction at Day 365 were reported.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Placebo matching to sifalimumab administered by intravenous infusion at a fixed dose of every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 200 Milligram (mg) n=33 Participants Sifalimumab 200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 600 mg n=33 Participants Sifalimumab 600 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 1,200 mg n=26 Participants Sifalimumab 1,200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.
Percentage of Participants With a Cutaneous Lupus Erythematosus Disease Activity and Severity Index (CLASI) Activity Score Greater Than or Equal to (>=) 10 at Baseline Who Achieved a >= 4-point Reduction Achieved >=4-point reduction: Yes	48.6 percentage of participants	72.7 percentage of participants	57.6 percentage of participants	73.1 percentage of participants
Percentage of Participants With a Cutaneous Lupus Erythematosus Disease Activity and Severity Index (CLASI) Activity Score Greater Than or Equal to (>=) 10 at Baseline Who Achieved a >= 4-point Reduction Achieved >=4-point reduction: No	51.4 percentage of participants	27.3 percentage of participants	42.4 percentage of participants	26.9 percentage of participants

SECONDARY outcome

Timeframe: Day 365

FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score).

Outcome measures

Outcome measures
Measure	Placebo n=105 Participants Placebo matching to sifalimumab administered by intravenous infusion at a fixed dose of every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 200 Milligram (mg) n=105 Participants Sifalimumab 200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 600 mg n=102 Participants Sifalimumab 600 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 1,200 mg n=101 Participants Sifalimumab 1,200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.
Percentage of Participants Who Achieved a Greater Than 3-Point Improvement in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Achieved > 3-point improvement: Yes	30.5 percentage of participants	38.1 percentage of participants	42.2 percentage of participants	35.6 percentage of participants
Percentage of Participants Who Achieved a Greater Than 3-Point Improvement in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Achieved > 3-point improvement: No	69.5 percentage of participants	61.9 percentage of participants	57.8 percentage of participants	64.4 percentage of participants

SECONDARY outcome

Timeframe: Day 1 up to Week 74

Population: The safety population included all participants who received any investigational product.

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent defined as events present at baseline that worsened in intensity after administration of investigational product or events absent at baseline that emerged after administration of investigational product, for the period extending until the end of participant participation in the study.

Outcome measures

Outcome measures
Measure	Placebo n=108 Participants Placebo matching to sifalimumab administered by intravenous infusion at a fixed dose of every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 200 Milligram (mg) n=108 Participants Sifalimumab 200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 600 mg n=108 Participants Sifalimumab 600 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 1,200 mg n=107 Participants Sifalimumab 1,200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) TEAE	94 participants	97 participants	97 participants	93 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) TESAE	19 participants	16 participants	22 participants	21 participants

SECONDARY outcome

Timeframe: Day 1 up to Week 61

Population: The safety population included all participants who received any investigational product.

Laboratory investigations included hematology, serum chemistries and urinalysis parameters. Participants with clinically significant abnormalities in these laboratory investigations recorded as TEAEs were reported.

Outcome measures

Outcome measures
Measure	Placebo n=108 Participants Placebo matching to sifalimumab administered by intravenous infusion at a fixed dose of every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 200 Milligram (mg) n=108 Participants Sifalimumab 200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 600 mg n=108 Participants Sifalimumab 600 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 1,200 mg n=107 Participants Sifalimumab 1,200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Hypoalbuminaemia	2 participants	0 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Low density lipoprotein increased	0 participants	1 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Blood albumin decreased	0 participants	0 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Anaemia	1 participants	4 participants	4 participants	2 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) White blood cell count increased	3 participants	1 participants	2 participants	3 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Neutrophil count increased	3 participants	1 participants	2 participants	2 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Iron deficiency anaemia	1 participants	2 participants	0 participants	2 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Haemoglobin decreased	0 participants	1 participants	0 participants	1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Lymphocyte count decreased	2 participants	1 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) White blood cell count decreased	1 participants	0 participants	1 participants	1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Autoimmune haemolytic anaemia	1 participants	1 participants	0 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Eosinophilia	0 participants	0 participants	0 participants	1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Haematocrit increased	0 participants	0 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Haemoglobin increased	0 participants	0 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Leukopenia	0 participants	1 participants	0 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Lymphopenia	1 participants	1 participants	0 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Neutropenia	3 participants	0 participants	0 participants	1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Neutrophil count decreased	1 participants	0 participants	0 participants	1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Platelet count increased	0 participants	0 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Red blood cell count decreased	0 participants	0 participants	0 participants	1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Thrombocytopenia	0 participants	1 participants	0 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Platelet count decreased	2 participants	0 participants	0 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Monocyte count increased	1 participants	0 participants	0 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Hypokalaemia	4 participants	1 participants	4 participants	5 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Alanine aminotransferase increased	5 participants	1 participants	1 participants	3 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Gamma-glutamyltransferase increased	5 participants	0 participants	1 participants	4 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Hypertriglyceridaemia	2 participants	1 participants	1 participants	3 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Dyslipidaemia	2 participants	0 participants	2 participants	2 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Hepatic enzyme increased	2 participants	2 participants	2 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Aspartate aminotransferase increased	2 participants	1 participants	0 participants	2 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Blood creatine phosphokinase increased	2 participants	0 participants	2 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Blood creatinine increased	0 participants	1 participants	0 participants	1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Blood glucose increased	1 participants	0 participants	0 participants	2 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Hyperglycaemia	1 participants	0 participants	0 participants	2 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Transaminases increased	1 participants	0 participants	1 participants	1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Blood potassium decreased	0 participants	1 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Blood alkaline phosphatase decreased	1 participants	0 participants	0 participants	1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Blood calcium increased	1 participants	0 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Blood cholesterol increased	0 participants	0 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Blood homocysteine increased	0 participants	0 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Liver function test abnormal	1 participants	0 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Hyperlipidaemia	0 participants	0 participants	0 participants	1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Hypoglycaemia	0 participants	0 participants	0 participants	1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Blood bilirubin increased	1 participants	0 participants	0 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Hypocalcaemia	1 participants	0 participants	0 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Blood triglycerides increased	1 participants	0 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Hyperbilirubinaemia	0 participants	0 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Hypertransaminasaemia	0 participants	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 up to Week 61

Population: The safety population included all participants who received any investigational product.

Vital sign assessments included blood pressure, pulse rate, temperature, weight and respiratory rate. Vital signs abnormalities recorded as TEAEs were reported.

Outcome measures

Outcome measures
Measure	Placebo n=108 Participants Placebo matching to sifalimumab administered by intravenous infusion at a fixed dose of every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 200 Milligram (mg) n=108 Participants Sifalimumab 200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 600 mg n=108 Participants Sifalimumab 600 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 1,200 mg n=107 Participants Sifalimumab 1,200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) Pyrexia	3 participants	2 participants	6 participants	7 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) Hypertension	7 participants	4 participants	5 participants	4 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) Weight increased	0 participants	1 participants	2 participants	2 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) Blood pressure increased	1 participants	2 participants	1 participants	0 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) Chills	1 participants	2 participants	0 participants	1 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) Hypertensive crisis	0 participants	0 participants	0 participants	1 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) Orthostatic hypotension	1 participants	0 participants	0 participants	1 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) Weight decreased	1 participants	0 participants	0 participants	1 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) Hypotension	1 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 up to Week 56

Population: The safety population included all participants who received any investigational product.

The 12-lead ECG data were summarized and evaluated. Number of participants with clinically significant abnormal ECG findings as assessed by cardiologist were recorded and reported as TEAEs.

Outcome measures

Outcome measures
Measure	Placebo n=108 Participants Placebo matching to sifalimumab administered by intravenous infusion at a fixed dose of every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 200 Milligram (mg) n=108 Participants Sifalimumab 200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 600 mg n=108 Participants Sifalimumab 600 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.	Sifalimumab 1,200 mg n=107 Participants Sifalimumab 1,200 mg administered by intravenous infusion every 2 weeks (14 days) for the first 3 doses (Days 1, 15, and 29) and then every 4 weeks (28 days) thereafter for 11 doses for a total of 14 doses.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Reported as TEAEs	2 participants	0 participants	1 participants	0 participants

Adverse Events

Placebo

Serious events: 19 serious events

Other events: 93 other events

Deaths: 0 deaths

Sifalimumab 200 mg

Serious events: 16 serious events

Other events: 94 other events

Deaths: 0 deaths

Sifalimumab 600 mg

Serious events: 22 serious events

Other events: 96 other events

Deaths: 0 deaths

Sifalimumab 1200 mg

Serious events: 21 serious events

Other events: 92 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Gabor Illei, MD, Senior Director, Clinical Development

MedImmune, LLC

Phone: 301-398-0000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome. The PIs also agree for data to be presented first as a joint, multi-center publication.
Publication restrictions are in place

Restriction type: OTHER