A Study to Evaluate the Continuous Safety and Efficacy of Litifilimab (BIIB059) in Adults With Active Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the long-term safety and tolerability of litifilimab in participants with active systemic lupus erythematosus (SLE). The secondary objectives of this study are to evaluate the long-term effect of litifilimab on disease activity in participants with SLE, to evaluate the long-term effect of litifilimab in participants with SLE in maintaining low disease activity, to evaluate the effect of litifilimab in participants with active SLE in preventing irreversible organ damage, to assess long-term use of oral corticosteroid (OCS) with participants receiving litifilimab treatment, to assess the impact of litifilimab on participant-reported Health-Related Quality-of-Life Questionnaire (HRQoL), symptoms, and impacts of SLE, to evaluate long-term effect of litifilimab on laboratory parameters, and to evaluate immunogenicity of litifilimab.

Detailed Description
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This is an extension study for all participants who completed study 230LE303 (NCT04895241) and 230LE304 (NCT04961567) (parent phase 3 studies) through Week 52 and did not discontinue litifilimab or placebo. Eligible participants from parent phase 3 studies will be followed for up to 180 weeks.

Official Title
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A Multicenter, Randomized, Dose-Blind, Phase 3 Long-Term Extension Study to Evaluate Continuous Safety and Efficacy of Litifilimab (BIIB059) in Adult Participants With Active Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus (SLE)

Intervention / Treatment
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* Drug: Litifilimab
* Drug: Litifilimab-matching placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participants who completed 1 of the 52-week of the double-blind placebo-controlled, parent Phase 3 studies (230LE303 (NCT04895241) and 230LE304 (NCT04961567)) on study treatments with either litifilimab or placebo to Week 48 and attended the last study assessment visit at Week 52 Key Exclusion Criteria: Early parent Phase 3 studies treatment terminators (participants who discontinued study treatment before Week 52) Early parent Phase 3 studies terminators (participants who withdrew from study participation and did not complete the 52 week treatment period) Participants who developed moderate-to-severe worsening of organ-specific lupus manifestations that would require a change in antimalarials and/or immunosuppressive therapy (initiation of new treatment or increase in dose above the allowed maximum dose) Use of other investigational drugs or off-label drugs used to treat SLE, cutaneous lupus, or lupus nephritis during the parent Phase 3 studies NOTE: Other inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Litifilimab Low Dose<br>Participants who are receiving background nonbiologic lupus standard of care (SOC) therapy and received litifilimab low dose, subcutaneously (SC), every 4 weeks (Q4W) during the parent Phase 3 studies (i.e. studies 230LE303 [NCT04895241] or 230LE304 [NCT04961567]) will continue to receive litifilimab low dose, SC, Q4W from Day 1 up to 152 weeks with an additional dose of litifilimab-matching placebo at Week 2. Participants who are receiving background nonbiologic lupus SOC therapy and received litifilimab-matching placebo in the parent Phase 3 studies (i.e. studies 230LE303 [NCT04895241] or 230LE304 [NCT04961567]) will be randomized to receive litifilimab low dose, SC, Q4W from Day 1 up to 152 weeks with an additional dose at Week 2. | Drug: Litifilimab<br>* Administered as specified in the treatment arm.<br>* Other names: BIIB059;Drug: Litifilimab-matching placebo<br>* Administered as specified in the treatment arm.<br>|
| Experimental: Litifilimab High Dose<br>Participants who are receiving background nonbiologic lupus SOC therapy and received litifilimab high dose, SC, Q4W during the parent Phase 3 studies (i.e. studies 230LE303 [NCT04895241] or 230LE304 [NCT04961567]) will continue to receive litifilimab high dose, SC, Q4W from Day 1 up to 152 weeks with an additional dose of litifilimab-matching placebo at Week 2. Participants who are receiving background nonbiologic lupus SOC therapy and received litifilimab-matching placebo in the parent Phase 3 studies (i.e. studies 230LE303 [NCT04895241] or 230LE304 [NCT04961567]) will be randomized to receive litifilimab high dose, SC, Q4W from Day 1 up to 152 weeks with an additional dose at Week 2. | Drug: Litifilimab<br>* Administered as specified in the treatment arm.<br>* Other names: BIIB059;Drug: Litifilimab-matching placebo<br>* Administered as specified in the treatment arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment Emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is an AE that started or worsened in severity after the first dose of study treatment through 28 days after the last dose of study treatment or end of study (EOS) date, whichever comes earlier. | Up to Week 180 | 
| Number of Participants with Serious Adverse Events (SAEs) | An SAE is any untoward medical occurrence that at any dose results in death, in the view of the Investigator, places the participant at immediate risk of death (a life threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, and is a medically important event. | Up to Week 180 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants who Achieved an Systemic Lupus Erythematosus Responder Index (SRI)-4 Response | SRI-4 is a composite endpoint defined as the following: A reduction from baseline of ≥4 points in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) score. No new organ system affected, as defined by no new British Isles Lupus Activity Group-2004 (BILAG-2004 grade A) and no more than 1 new BILAG 2004 grade B versus previous visit. No worsening from baseline in lupus disease activity as defined by <0.3-point increase on 3-point Physician's Global Assessment (PGA) visual analog scale (VAS). No violation of protocol-specified medication rules | Up to Week 180 | 
| Percentage of Participants who Achieved a Joint-50 Response | Joint-50 response is a 50% reduction in total active joint count from baseline. An active joint is defined as a joint with pain and signs of inflammation (e.g., tenderness, swelling or effusion). A 28-joint assessment will be performed to determine the active joint count, which is defined as the sum of tender and swollen joint counts. | Up to Week 180 | 
| Percentage of Participants who Achieved Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-50, CLASI-70, and CLASI-90 Response | CLASI score is used to evaluate lupus skin manifestations. The activity scale (CLASI-A) includes measurements of erythema, scale and hypertrophy, and mucous membrane disease. Each part of the body is listed separately, from the scalp to the feet, in addition to sections focusing on mucous membrane involvement and alopecia. Points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. Scores for each area are assigned based on the most severe lesion within the area of interest. CLASI-A scores of 0 to 9, 10 to 20, and 21 to 70 represent disease severity of mild, moderate, and severe, respectively. CLASI-50 is 50% of improvement from baseline in CLASI-A. CLASI-70 is 70% of improvement from baseline in CLASI-A and CLASI-90 is 90% of improvement from baseline in CLASI-A. | Up to Week 180 | 
| Percentage of Participants who Achieved a British Isles Lupus Assessment Group based Composite Lupus Assessment (BICLA) Response | BICLA is a composite endpoint defined as the following: BILAG-2004 improvement, defined as all of BILAG-2004 Grade A at Baseline improved to B, C, or D and all of BILAG-2004 Grade B at Baseline improved to C or D. No BILAG-2004 worsening in other BILAG-2004 organ systems such that there are no new BILAG-2004 Grade A or greater than 1 new BILAG-2004 Grade B. No worsening in the SLEDAI-2K total score compared to baseline. No worsening from baseline in lupus disease activity defined by a <0.3-point increase on a 3-point PGA VAS. No violation of protocol-specified medication rules. | Up to Week 180 | 
| Annualized Severe Safety of Estrogens in Systemic Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index Flare Index (SFI) Flare Rate | A severe flare is defined as any of the following: Change in SLEDAI instrument score to >12 New or worse: central nervous system SLE; vasculitis; nephritis; myositis; platelets <60,000/mL, or hemolytic anemia with hemoglobin <7 grams per deciliter (g/dL) or decrease in hemoglobin >3 g/dL and requiring: doubling prednisone dose, increase to >0.5 milligrams per kilograms per day (mg/kg/day) or hospitalization Increase in prednisone dose to >0.5 mg/kg/day New requirement for cyclophosphamide, azathioprine, methotrexate, or mycophenolate for SLE activity Hospitalization for SLE activity Increase in PGA score to >2.5 | Up to Week 156 | 
| Percentage of Time Spent in Lupus Low Disease Activity State (LLDAS) | LLDAS is a composite endpoint defined as the following: i. SLEDAI-2K score ≤ 4, with no activity in a major organ system (renal, central nervous system, cardiopulmonary, vasculitis, fever); and ii. No new features of lupus disease activity compared with the previous assessment; and iii. SELENA-SLEDAI PGA ≤ 1; and iv. Current prednisone (or equivalent) dose ≤ 7.5 mg/day; and v. Standard maintenance doses of immunosuppressive drugs and approved biological agents. No new features is defined as any new SLEDAI-2K component that was not present at the previous assessment. The SELENA-SLEDAI PGA Scale ranges from 0-3, where 0 is no disease activity and 3 is maximum disease activity. Standard maintenance doses include drugs limited to those allowed per protocol. | Up to Week 180 | 
| Percentage of Participants With Sustained LLDAS | LLDAS is a composite endpoint defined as the following: i. SLEDAI-2K score ≤ 4, with no activity in a major organ system (renal, central nervous system, cardiopulmonary, vasculitis, fever); and ii. No new features of lupus disease activity compared with the previous assessment; and iii. SELENA-SLEDAI PGA ≤ 1; and iv. Current prednisone (or equivalent) dose ≤ 7.5 mg/day; and v. Standard maintenance doses of immunosuppressive drugs and approved biological agents. No new features is defined as any new SLEDAI-2K component that was not present at the previous assessment. The SELENA-SLEDAI PGA Scale ranges from 0-3, where 0 is no disease activity and 3 is maximum disease activity. Standard maintenance doses include drugs limited to those allowed per protocol. | Up to Week 180 | 
| Duration of Sustained LLDAS as Defined by the Number of Visits in LLDAS | LLDAS is a composite endpoint defined as the following: i. SLEDAI-2K score ≤ 4, with no activity in a major organ system (renal, central nervous system, cardiopulmonary, vasculitis, fever); and ii. No new features of lupus disease activity compared with the previous assessment; and iii. SELENA-SLEDAI PGA ≤ 1; and iv. Current prednisone (or equivalent) dose ≤ 7.5 mg/day; and v. Standard maintenance doses of immunosuppressive drugs and approved biological agents. No new features is defined as any new SLEDAI-2K component that was not present at the previous assessment. The SELENA-SLEDAI PGA Scale ranges from 0-3, where 0 is no disease activity and 3 is maximum disease activity. Standard maintenance doses include drugs limited to those allowed per protocol. | Up to Week 180 | 
| Annual Change From Baseline Value From the Parent Phase 3 Studies in Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) Score | SDI score is used to assess the accumulated damage in participants with SLE. It assess 12 organ systems and records damage in participants with lupus, regardless of its cause. Damage could be due to previous disease activity, medication, or intercurrent illness (such as surgery or cancer). To distinguish between active inflammation and damage, an item must be present for at least 6 months. It is assumed that persistent inflammation (for at least 6 months) would result in tissue injury and hence damage. SDI is evaluated on a scale 0-47 with higher score indicating higher damage. | Up to Week 156 | 
| Cumulative Exposure to OCS Over Time |  | Up to Week 156 | 
| Percentage of Participants With OCS ≤7.5 mg |  | Up to Week 156 | 
| Percentage of Participants With OCS ≤5 mg |  | Up to Week 156 | 
| Change From Baseline in Lupus-Specific Health-Related Quality-Of-Life (LupusQoL) Score | The LupusQoL is a participant-reported, lupus-specific, HRQoL questionnaire consisting of 34 items grouped in 8 domains: physical health, pain, planning, intimate relationships, burden to others, emotional health, body image and fatigue. Participants indicate their responses on a 5-point Likert response format, where 4 = never, 3 = occasionally, 2 = a good bit of the time, 1 = most of the time, and 0 = all the time. A LupusQoL score for each domain will be reported on a 0 to 100 scale, with greater values indicating better HRQoL. | Up to Week 156 | 
| Change From Baseline in Short Form Health Survey-36 (SF-36) (Acute Version) Score | The SF-36 is a 36-item scale which assesses HRQoL in 8 domains: limitations in physical activities due to health problems, limitations in social activities due to physical or emotional problems, limitations in usual role activities due to physical health problems, bodily pain, general mental health (psychological distress and well-being), limitations in usual role activities due to emotional problems, vitality (energy and fatigue), general health perceptions. The SF-36 (Acute Version) form asks for participants to reply to questions (items) according to how they have felt over a specifically defined period of time. Items 1-4 primarily contribute to the physical component summary (PCS) score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36 where higher scores indicate best health. Scores on each item are summed and averaged (range: 0=worse health to 100=best possible health). | Up to Week 156 | 
| Change From Baseline in European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L) | The EQ-5D is a standardized generic measure of health status developed by the European Quality of Life Group. This study uses the EQ-5D-3L version of the instrument. This instrument consists of 2 sections. The first section comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. All dimensions are measured on a 3-point scale, 1: No problems; 2: Some problems; 3: Extreme problems. The second section comprises the Visual Analogue Scale, which records the respondent's self-rated health on a vertical scale ranging from 0 to 100, lower scores indicate the worst possible health state. | Up to Week 156 | 
| Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score | The FACIT-Fatigue is a participant-administered HRQoL questionnaire that evaluates participant's fatigue in 5 broad categories: physical well-being, social/family well-being, emotional well-being, functional well-being and additional concerns. The level of fatigue is measured by questions assessed on a 5-point scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The responses for each item are added to obtain a total score which ranges from 0 to 52, with a higher score indicating less fatigue. | Up to Week 156 | 
| Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Score | The PHQ-9 is a participant-administered HRQoL questionnaire to screen for the presence and severity of depression. The PHQ-9 is a participant-reported outcome (PRO) that is used to measure depression in adults. It contains 9 questions, with a 2 week recall period. The PHQ-9 yields an overall severity score that can range from 0 to 27 with the following severity scores: 0-4 = none; 5-9 = mild; 10-14 = moderate; 15-19 = moderate-to-severe; and 20-27 = severe. | Up to Week 156 | 
| Change From Baseline in Work Productivity and Activity Impairment (WPAI):Lupus Score | WPAI questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (work time missed) 2. Presenteesism (impairment at work / reduced on-the-job effectiveness) 3. Work productivity loss (overall work impairment / absenteeism plus presenteeism) 4. Activity Impairment. Each score ranges from 0 to 100, with higher numbers indicating greater impairment and less productivity. | Up to Week 156 | 
| Change from Baseline in Patient Global Assessment (PtGA) Score | The PtGA is participant-administered, single-item question evaluating the impact of health and illness, with responses ranging from very poor to very well on a 100 mm VAS. The participant will consider the previous week when addressing this question. | Up to Week 156 | 
| Number of Participants with Clinically Relevant Abnormalities in Standard Laboratory Parameters | Standard laboratory parameters will include hematology, blood chemistry, urinalysis, and coagulation. | Up to Week 180 | 
| Number of Participants with Clinically Relevant Abnormalities in Electrocardiogram (ECG) Results |  | Up to Week 156 | 
| Number of Participants with Antibodies to Litifilimab |  | Up to Week 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lupus Erythematosus, Systemic Autoimmune Diseases, Connective Tissue Diseases, Immune System Diseases