A 2-Part Phase 2 Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of BIIB059 in Subjects With Systemic Lupus Erythematosus and Active Skin Manifestations and in Subjects With Active Cutaneous Lupus Erythematosus With or Without Systemic Manifestations
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 264
- 试验地点
- 54
- 主要终点
- Part A: Change From Baseline in Active Joint Count (28-joint Assessment) to Week 24
研究概览
简要总结
The primary purpose of the study is to evaluate the efficacy of BIIB059 (litifilimab) in reducing disease activity in participants with systemic lupus erythematosus (SLE) with active cutaneous manifestations and joint involvement (Part A), and in participants with active cutaneous lupus erythematosus (CLE) (Subacute cutaneous lupus erythematosus (SCLE) or chronic CLE, including discoid lupus erythematosus (DLE)) with or without systemic manifestations (Part B). The secondary objective is to evaluate additional efficacy parameters of BIIB059 in reducing SLE/CLE disease activity, pharmacokinetic parameters, safety and tolerability of BIIB059 (Parts A and B).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of systemic lupus erythematosus (SLE) fulfilling at least 4 out of 11 of the 1997 revised American College of Rheumatology (ACR) classification criteria for SLE along with active skin manifestations and joint involvement.
- •At least 4 tender joints and at least 4 swollen joints with at least 4 of the swollen joints in the proximal interphalangeal (PIP) joints, metacarpophalangeal (MCP) joints and/or wrist.
- •Demonstrate at least one sign of active lupus skin disease, including acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), and/or chronic cutaneous lupus erythematosus (CCLE) (e.g., discoid lupus erythematosus (DLE)), with skin activity defined by SLE Disease Activity Index 2000 (SLEDAI-2K) at the time of Screening and randomization.
- •Active skin manifestations Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) ≥8)) and a diagnosis of cutaneous lupus erythematosus (CLE) that has been histologically confirmed (in the past or at Screening), with or without SLE manifestations.
排除标准
- •Active lupus nephritis or moderate-to-severe or chronic kidney disease.
- •Any active skin conditions other than CLE that may interfere with the study (e.g., psoriasis, non-LE skin lupus, drug-induced lupus).
- •History of chronic, recurrent (3 or more of the same type of infection in a 12-month period), or recent serious infection (e.g., pneumonia, septicemia, herpes zoster) as determined by the Investigator and requiring anti-infective treatment within 12 weeks prior to Screening.
- •Use of immunosuppressive or disease-modifying treatments for SLE or CLE that were initiated less than 12 weeks prior to Randomization.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Part A: BIIB059 450 mg
BIIB059 450 mg administered SC, Q4W with an additional dose at Week 2 for a total of 7 doses (Weeks 0, 2, 4, 8, 12, 16, and 20) in participants with SLE with active skin manifestations and joint involvement.
干预措施: BIIB059 (litifilimab) (Drug)
Part A: Placebo
BIIB059 matching placebo administered SC, Q4W with an additional dose at Week 2 for total of 7 doses (Weeks 0, 2, 4, 8, 12, 16, and 20) in participants with SLE with active skin manifestations and joint involvement.
干预措施: Placebo (Drug)
Part B: BIIB059 50 mg
BIIB059 50 mg administered SC, Q4W with an additional loading dose at Week 2 for a total of 5 doses (Weeks 0, 2, 4, 8, and 12) in participants with active CLE with or without systemic manifestations.
干预措施: BIIB059 (litifilimab) (Drug)
Part B: BIIB059 150 mg
BIIB059 150 mg administered SC, Q4W with an additional loading dose at Week 2 for a total of 5 doses (Weeks 0, 2, 4, 8, and 12) in participants with active CLE with or without systemic manifestations.
干预措施: BIIB059 (litifilimab) (Drug)
Part B: BIIB059 450 mg
BIIB059 450 mg administered, Q4W with an additional loading dose at Week 2 for a total of 5 doses (Weeks 0, 2, 4, 8, and 12) in participants with active CLE with or without systemic manifestations.
干预措施: BIIB059 (litifilimab) (Drug)
Part B: Placebo
BIIB059 matching placebo administered SC, Q4W with an additional loading dose at Week 2 for a total of 5 doses (Weeks 0, 2, 4, 8, and 12) in participants with active CLE with or without systemic manifestations.
干预措施: Placebo (Drug)
结局指标
主要结局
Part A: Change From Baseline in Active Joint Count (28-joint Assessment) to Week 24
时间窗: Baseline to Week 24
An active joint is defined as a joint with pain and signs of inflammation (e.g., tenderness, swelling or effusion). The 28 Joint Count includes assessment of swelling and tenderness in the shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints and knees. The investigator counts how many of the 28 joints are swollen or tender at the given week.
Part B: Percent Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score to Week 16
时间窗: Baseline to Week 16
The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a clinical tool that quantifies disease activity and damage in cutaneous lupus erythematosus (CLE). 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. Composite scores are calculated by summing the individual component scores. CLASI-A scores of 0-9, 10-20, and 21-70 represent disease severity of mild, moderate, and severe, respectively. Higher scores indicate more disease activity.
次要结局
- Part A: Percentage of Participants With a >=4-point Reduction From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 24(Week 24)
- Part B: Percentage of Participants With a >=7-point Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 12 and 16(Week 12, Week 16)
- Part B: Percentage of Participants With Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity- 50 (CLASI-50) Response at Week 12 and 16(Week 12, Week 16)
- Part A: Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Score at Week 24(Baseline to Week 24)
- Part B: Percent Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 12(Baseline, Week 12)
- Part A: Percentage of Participants With a >=7-point Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 24(Week 24)
- Part A: Percentage of Participants Achieving a Systemic Lupus Erythematosus (SLE) Responder Index >=4 (SRI-4) at Week 24(Week 24)
- Part B: Number of Participants With Clinically Significant Laboratory Assessment Abnormalities(Baseline up to Week 28)
- Part A : Percentage of Participants With Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity- 50 (CLASI-50) Response at Week 24(Week 24)
- Part B: Percentage of Participants With a >=4-point Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 12 and 16(Week 12, Week 16)
- Part B: Number of Participants With Positive BIIB059 Antibodies(Baseline up to Week 16)
- Part A: Absolute Change From Baseline Over Time in Immunoglobulin Levels(Baseline up to Week 24)
- Part B: Percent Change From Baseline Over Time in Immunoglobulin Levels(Baseline up to Week 16)
- Part B: Serum Concentration of BIIB059(Part B: pre-dose on Days 1, 29, 85 and post-dose on Days 1, 29, 85, 113, 141, 169 and 197)
- Part A: Percent Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 12, 16 and 24(Baseline, Week 12, 16 and 24)
- Part A: Percentage of Participants With no New Organ System Affected at Week 24(Week 24)
- Part A: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to Week 36)
- Part B: Absolute Change From Baseline in Vaccine Titers - Clostridium Tetani (C. Tetani) and Diphtheria at Week 12(Baseline to Week 12)
- Part A: Percent Change From Baseline Over Time in Immunoglobulin Levels(Baseline up to Week 24)
- Part A: Number of Participants With Clinically Significant 12-Lead Electrocardiograms (ECGs) Abnormalities(Baseline up to Week 36)
- Part A: Number of Participants With Positive BIIB059 Antibodies(Baseline up to Week 24)
- Part B: Absolute Change From Baseline in Vaccine Titers - Streptococcus Pneumoniae (S. Pneumoniae) at Week 12(Baseline to Week 12)
- Part A: Absolute Change From Baseline in Vaccine Titers - Clostridium Tetani (C. Tetani) and Diphtheria at Week 24(Baseline to Week 24)
- Part A: Serum Concentration of BIIB059(Part A: pre-dose on Days 1, 29, 85 and 113 and post-dose on Days 1, 8, 29, 85, 169, 197 and 253)
- Part A: Change From Baseline in Physician's Global Assessment (PGA) of SLE Visual Analog Scale (VAS) Score at Week 24(Baseline to Week 24)
- Part B: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to Week 28)
- Part A: Number of Participants With Clinically Significant Laboratory Assessment Abnormalities(Baseline up to Week 36)
- Part B: Number of Participants With Clinically Significant 12-Lead Electrocardiograms (ECGs) Abnormalities(Baseline up to Week 28)
- Part A: Percent Change From Baseline in Vaccine Titers at Week 24(Baseline to Week 24)
- Part B: Percent Change From Baseline in Vaccine Titers at Week 12(Baseline to Week 12)
- Part A: Number of Participants With Clinically Significant Vital Sign Abnormalities(Baseline up to Week 36)
- Part B: Number of Participants With Clinically Significant Vital Sign Abnormalities(Baseline up to Week 28)
- Part B: Absolute Change From Baseline Over Time in Immunoglobulin Levels(Baseline up to Week 16)
- Part A: Absolute Change From Baseline in Vaccine Titers - Streptococcus Pneumoniae (S. Pneumoniae) at Week 24(Baseline to Week 24)