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

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of sifalimumab compared to placebo in subjects with moderately to severely active Systemic Lupus Erythematosus (SLE).

Detailed Description
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This is a Phase 2b, multinational, multicenter, randomized, double-blind, placebo controlled, parallel group study to evaluate the efficacy and safety of three intravenous (IV) treatment regimens of sifalimumab (200, 600, or 1,200 mg) in adult subjects with chronic moderately-to-severely active SLE with an inadequate response to standard of care (SOC) for SLE.

Official Title
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A Phase 2b, Dose-ranging Study to Evaluate the Efficacy and Safety of Sifalimumab in Adults With Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Biological: Sifalimumab 200 mg
* Biological: Sifalimumab 600 mg
* Biological: Sifalimumab 1,200 mg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Fulfills at least 4 of American College of Rheumatology (ACR) criteria for systemic lupus erythematosus (SLE) including a positive antinuclear antibody (ANA) or elevated ds-deoxyribonucleic acid (DNA) or Sm antibody at screening - Disease history of SLE greater than or equal to (>=) 24 weeks at screening - Weight more than (>) 40 kilogram (kg) - Currently receiving stable dose of oral prednisone and/or antimalarials/immunosuppressives - Active moderate to severe SLE disease based on SLE disease activity score (SLEDAI) and British Isles Lupus Assessment Group Index (BILAG) and Physicians Global Assessment - No evidence of cervical malignancy on PAP within 6 months of randomization - Female subjects must be willing to avoid pregnancy - Negative TB test or newly positive TB test due to latent TB for which treatment must be initiated at or before randomization. Exclusion Criteria: - Active severe SLE-driven renal disease or unstable renal disease prior to screening - Active severe or unstable neuropsychiatric SLE - Clinically significant active infection including ongoing and chronic infections - History of human immunodeficiency virus (HIV) - Confirmed Positive tests for Hepatitis B or positive test for hepatitis C - History of severe herpes infection such as herpes encephalitis, ophthalmic herpes, disseminated herpes - Herpes Zoster within 3 months of screening - History of cancer other than basal cancer or cervical cancer treated with apparent success >=1 year prior to randomization - Receipt of a biologic agent within 5 half-lives or prior to loss of pharmacodynamic and/or clinical effect (whichever is longer) prior to screening - Live or attenuated vaccine within 4 weeks prior to screening - Subjects with substance abuse - Subjects with significant hematologic abnormalities.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sifalimumab 200 milligram (mg)<br>Sifalimumab 200 milligram (mg) will be administered intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses. | Biological: Sifalimumab 200 mg<br>* Sifalimumab 200 mg intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.<br>* Other names: MEDI-545;|
| Experimental: Sifalimumab 600 mg<br>Sifalimumab 600 mg will be administered intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses. | Biological: Sifalimumab 600 mg<br>* Sifalimumab 600 mg intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.<br>* Other names: MEDI-545;|
| Experimental: Sifalimumab 1,200 mg<br>Sifalimumab 1,200 mg will be administered intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses. | Biological: Sifalimumab 1,200 mg<br>* Sifalimumab 1,200 mg intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.<br>* Other names: MEDI-545;|
| Placebo Comparator: Placebo<br>Placebo matching to sifalimumab will be administered intravenously at a fixed dose every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses. | Other: Placebo<br>* IV Placebo every 2 weeks for 4 weeks and then monthly for 44 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Response in Systemic Lupus Erythematosus Responder Index 4 (SRI [4]) | 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). | Day 365 | 
| Percentage of Participants Achieving a Positive Response in SRI (4) in 4-Gene Interferon Test High Participants | 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). | Day 365 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Day 365 | 
| 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 | 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. | Day 365 | 
| Percentage of Participants Who Achieved a Greater Than 3-Point Improvement in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale | 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). | Day 365 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) | 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. | Day 1 up to Week 74 | 
| Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) | Laboratory investigations included hematology, serum chemistries and urinalysis parameters. Participants with clinically significant abnormalities in these laboratory investigations recorded as TEAEs were reported. | Day 1 up to Week 61 | 
| Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) | Vital sign assessments included blood pressure, pulse rate, temperature, weight and respiratory rate. Vital signs abnormalities recorded as TEAEs were reported. | Day 1 up to Week 61 | 
| Number of Participants With Abnormal Electrocardiogram (ECG) Findings Reported as TEAEs | 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. | Day 1 up to Week 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLE, Systemic Lupus Erythematosus, Sifalimumab, MEDI-545