The WILLOW Study With M5049 in SLE and CLE (SCLE and/or DLE) (WILLOW)
Phase 2
Completed
- Conditions
- Systemic Lupus Erythematosus
- Interventions
- Drug: Enpatoran medium doseDrug: Enpatoran high doseDrug: Enpatoran low doseDrug: Placebo
- Registration Number
- NCT05162586
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 456
Inclusion Criteria
- 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
Exclusion Criteria
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A: Enpatoran medium dose 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. Cohort B (Part 1 + Part 2): Enpatoran high dose 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. Cohort A: Enpatoran low dose 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. Cohort B (Part 1 + Part 2): Placebo 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 . Cohort B (Part 2): Enpatoran low dose 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. Cohort A: Placebo 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. Cohort B (Part 2): Enpatoran medium dose 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. Cohort A: Enpatoran high dose 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.
- Primary Outcome Measures
Name Time Method Cohort A: Percent Change from Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-A) at Week 16 Baseline, Week 16 Cohort B: British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response at Week 24 At Week 24
- Secondary Outcome Measures
Name Time Method Cohort A and Cohort B: Change from Baseline in Physician's Global Assessment of Cutaneous Lupus Disease Activity at Week 16 and 24 Baseline, Week 16 and 24 Cohort B: Remission Attainment at Week 24 At Week 24 Cohort A: Clinically Meaningful Corticosteroids (CS) Reduction Day 1 up to Week 24 CS reduction is defined as the reduction of daily prednisone-equivalent dose from \>= 10 mg at Day 1 to \<= 5 mg by the Week 12 visit and sustained through Week 24.
Cohort A: Ocurrence of Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) Score 0 or 1 at Week 16 and Week 24 At Week 16 and 24 Cohort B: Systemic lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24 At Week 24 Cohort B: Change from Baseline in Physician's Global Assessment at Week 24 Baseline, Week 24 Cohort A and Cohort B: Safety Profile as Assessed by Incidence of Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), AEs of Special Interest, Clinically Significant Abnormalities in Laboratory Parameters and QT Interval Corrected Baseline (Day 1) up to End of Safety Follow-up Period (Week 33) Cohort A and Cohort B: Change from Baseline in Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) at Week 16 and Week 24 Baseline, Week 16 and 24 Cohort B: Participants with British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response and with Clinically Meaningful Corticosteroids (CS) Reduction Day 1 up to Week 24 CS reduction is defined as the reduction of daily prednisone-equivalent dose from \>= 10 mg at Day 1 to \<= 5 mg by the Week 12 visit and sustained through Week 24.
Cohort B: Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare Day 1 through Week 24 Cohort B: Lupus Low Disease Activity State (LLDAS) Attainment at Week 24 At Week 24 Cohort A and B: Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scores at Week 24 Baseline, Week 24 Cohort B: Change From Baseline in Tender Joint Count and Swollen Joint Count at Week 24 Baseline, Week 24 Cohort B: Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare Day 1 through Week 24 Cohort A and B: Change from Baseline in Skindex 29+3 Symptom Domain Score at Week 24 Baseline, Week 24 Cohort A and B: Change from Baseline in the Skindex 29+3 Functioning and Emotion Domain Scores at Week 24 Baseline, Week 24 Change from Baseline in the Skindex 29+3 Lupus-Specific Domain Score at Week 24 Baseline, Week 24
Related Research Topics
Explore scientific publications, clinical data analysis, treatment approaches, and expert-compiled information related to the mechanisms and outcomes of this trial. Click any topic for comprehensive research insights.
What molecular mechanisms and targets does Enpatoran modulate in systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE) to exert its therapeutic effects?
How does Enpatoran's efficacy in treating SLE and CLE compare to standard-of-care therapies in Phase II clinical trials?
Which biomarkers are being evaluated in the WILLOW study (NCT05162586) to predict patient response to Enpatoran in SLE and CLE subtypes?
What are the known or potential adverse events associated with Enpatoran in SLE and CLE patients, and how are they managed in clinical trials?
Are there other TLR7/8 inhibitors or combination therapies in development for SLE and CLE, and how does Enpatoran compare to these approaches?
Trial Locations
- Locations (153)
The Lundquist Institute at Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
Bay Area Arthritis and Osteoporosis
🇺🇸Brandon, Florida, United States
Charisma Medical and Research Center
🇺🇸Miami Lakes, Florida, United States
Advance Medical Research Center
🇺🇸Miami, Florida, United States
New Horizon Research Center, Inc
🇺🇸Miami, Florida, United States
HMD Research, LLC
🇺🇸Orlando, Florida, United States
D&H Tamarac Research Center, LLC
🇺🇸Tamarac, Florida, United States
RNA America Health Sciences
🇺🇸Sugar Hill, Georgia, United States
Dawes Fretzin Dermatology Group, LLC
🇺🇸Indianapolis, Indiana, United States
AA MRC LLC Ahmed Arif Medical Research Center
🇺🇸Grand Blanc, Michigan, United States
Scroll for more (143 remaining)The Lundquist Institute at Harbor-UCLA Medical Center🇺🇸Torrance, California, United States