A Phase II, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging, Parallel and Adaptive Study to Evaluate the Efficacy and Safety of Enpatoran in SLE and in CLE (SCLE and/or DLE) Participants Receiving Standard of Care (WILLOW)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 456
- 试验地点
- 153
- 主要终点
- Cohort A: Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index-A (CLASI-A) Total Score at Week 16
研究概览
简要总结
The purpose of this Proof of Concept (PoC) and Dose-finding (DF) basket study is to evaluate the efficacy and safety of orally administered Enpatoran over 24 weeks in systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE; subacute cutaneous lupus erythematosus [SCLE] and/or discoid lupus erythematosus [DLE]) participants in a randomized, double-blind, placebo-controlled, parallel, adaptive and dose-ranging setting. Study Duration: 33 weeks Visit Frequency: every 2 or 4 weeks Enpatoran is not available through an expanded access program.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Active CLE (SCLE and/or DLE) with a CLE disease area and activity index (CLASI-A) >= 8
- •Active SLE with presence of: CLASI-A >= 8 and BILAG 2004 1B, C, D (that is [i.e.], No BILAG 2004 A and No BILAG 2004 >= 2B) or BILAG 2004 >= 1A or 2B and 1 or 2 of the following: Hybrid Safety of Estrogens in Systemic Lupus Erythematosus National Assessment (SELENA)-SLEDAI >= 6 at Screening Visit and confirmed clinical hybrid SELENA-SLEDAI >= 4 (excluding laboratory parameters) at Day 1 Visit and/or CLASI-A >= 8
- •Receiving a stable dose of at least one of the following standards of care therapies for lupus: Immunomodulator/immunosuppressant, oral corticosteroids, and/or topical corticosteroids
- •Other protocol defined inclusion criteria could apply
排除标准
- •Autoimmune or rheumatic disease other than SLE or CLE
- •Dermatological diseases other than cutaneous manifestations of SLE or CLE
- •Uncontrolled medical conditions including significant cardiovascular events, active lupus nephritis, and active neurological disorder
- •Ongoing or active clinically significant viral, bacterial, or fungal infection
- •History of uncontrolled seizures or other neurological disorder
- •History of or positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B virus
- •History of malignancy
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Cohort A: Placebo
Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (Cutaneous Lupus Erythematosus Disease Area and Severity Index [CLASI-A] greater than or equal to [>=] 8) will be enrolled in Cohort A to receive placebo matched to Enpatoran.
干预措施: Placebo (Drug)
Cohort A: Enpatoran low dose
Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (CLASI-A >= 8) will be enrolled in Cohort A to receive low dose of Enpatoran.
干预措施: Enpatoran low dose (Drug)
Cohort A: Enpatoran medium dose
Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (CLASI-A >= 8) will be enrolled in Cohort A to receive medium dose of Enpatoran.
干预措施: Enpatoran medium dose (Drug)
Cohort A: Enpatoran high dose
Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (CLASI-A >= 8) will be enrolled in Cohort A to receive high dose of Enpatoran.
干预措施: Enpatoran high dose (Drug)
Cohort B (Part 1 + Part 2): Placebo
Participants with active SLE who have moderate to high systemic disease activity (British Isles Lupus Assessment Group [BILAG A/2B]) with 1 or 2 of the following: CLASI-A >= 8 and/or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) >= 6 will be enrolled in Cohort B to receive placebo matched to Enpatoran .
干预措施: Placebo (Drug)
Cohort B (Part 1 + Part 2): Enpatoran high dose
Participants with active SLE who have moderate to high systemic disease activity (BILAG A/2B) with 1 or 2 of the following: CLASI-A >= 8 and/or SLEDAI >= 6 will be enrolled in Cohort B to receive high dose of Enpatoran.
干预措施: Enpatoran high dose (Drug)
Cohort B (Part 2): Enpatoran low dose
Participants with active SLE who have moderate to high systemic disease activity (BILAG A/2B) with 1 or 2 of the following: CLASI-A >= 8 and/or SLEDAI >= 6 will be enrolled in Cohort B to receive low dose of M5049.
干预措施: Enpatoran low dose (Drug)
Cohort B (Part 2): Enpatoran medium dose
Participants with active SLE who have moderate to high systemic disease activity (BILAG A/2B) with 1 or 2 of the following: CLASI-A >= 8 and/or SLEDAI >= 6 will be enrolled in Cohort B to receive medium dose of Enpatoran.
干预措施: Enpatoran medium dose (Drug)
结局指标
主要结局
Cohort A: Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index-A (CLASI-A) Total Score at Week 16
时间窗: Baseline, week 16
The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index) was a validated instrument used to assess disease activity (CLASI-A) and damage in lupus erythematosus. The activity scale included erythema, scale/hypertrophy, active alopecia, recent hair loss, and mucous membrane disease, while the damage scale measured dyspigmentation, atrophy, and scarring. CLASI-A scores ranged from 0 to 70, with mild, moderate, and severe disease corresponding to scores of 0-9, 10-20, and 21-70, respectively. Erythema and scale/hypertrophy sub-scores were computed across 13 body areas, with maximum scores of 39 and 26, respectively. The remaining 5 points reflected contributions from active alopecia (0-3), recent hair loss (0-1), and mucous membrane involvement (0-1), completing the total CLASI-A activity score. Directionality reflected worsening with higher scores and improvement with lower scores.
Cohort B: Number of Participants With British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response at Week 24
时间窗: At Week 24
BILAG-based BICLA response is defined as participants meeting all of the following criteria: 1. Improvement in baseline BILAG scores in all organ systems with moderate or severe disease activity-i.e., all grade A scores (severe disease requiring high-dose therapy) must improve to B (moderate), C (mild), or D (no activity); all grade B scores (moderate disease requiring moderate therapy) must improve to C or D; 2. No new BILAG A scores and no more than one new BILAG B score; 3. No worsening in total SLEDAI-2K score from baseline; 4. No significant deterioration (≤10%) in physician's global assessment; and 5. No treatment failure, defined as initiation of non-protocol therapy. Directionality is toward clinical improvement and disease stabilization.
次要结局
- Cohort A and B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events (AEs) of Special Interest(From screening upto safety follow up period (up to approximately 33 weeks))
- Cohort A and B: Number of Participants With Abnormal Laboratory Parameters(From screening upto safety follow up period (up to approximately 33 weeks))
- Cohort A and B: Number of Participants With Clinically Important Increases in QT Interval Corrected Using Fridericia's Formula (QTcF)(From screening upto safety follow up period (up to approximately 33 weeks))
- Cohort A and Cohort B: Change From Baseline in Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) Scale Score at Week 16 and Week 24(Baseline and at Week 16 and Week 24)
- Cohort A and Cohort B: Change From Baseline in Physician's Global Assessment of Cutaneous Lupus Disease Activity Score at Week 16 and 24(Baseline and at Week 16 and Week 24)
- Cohort B: Number of Participants With Both BICLA Response and With Clinically Meaningful Corticosteroids (CS) Reduction(At week 24 (BICLA Response) and Day 1 upto Week 24 (CS Reductions))
- Cohort A and B: Number of Participants With Clinically Meaningful Corticosteroids (CS) Reduction(Day 1 up to Week 24)
- Cohort A: Number of Participants With CLA-IGA Score 0 or 1 at Week 16 and Week 24(At Week 16 and Week 24)
- Cohort B: Number of Participants With Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24(At Week 24)
- Cohort B: Number of Participants With Lupus Low Disease Activity State (LLDAS) Attainment at Week 24(At Week 24)
- Cohort B: Number of Participants With Remission Attainment at Week 24(At Week 24)
- Cohort B: Percentage of Participants With 50% Reduction in Baseline Tender and Swollen Count at Week 24(At Week 24)
- Cohort B: Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare(Baseline (Day 1) through Week 24)
- Cohort B: Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare(Baseline (Day 1) through Week 24)
- Cohort A and B: Change From Baseline in Skindex 29+3 Symptom Domain Score at Week 24(Baseline and at week 24)
- Cohort A and B: Change From Baseline in the Skindex 29+3 Functioning Domain Scores at Week 24(Baseline and at Week 24)
- Cohort A and B: Change From Baseline in the Skindex 29+3 Emotion Domain Scores at Week 24(Baseline and at Week 24)
- Cohort A and B: Change From Baseline in the Skindex 29+3 Lupus-Specific Domain Scores at Week 24(Baseline and at Week 24)
- Cohort A and B: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scores at Week 24(Baseline and at Week 24)