Phase 2
N=456
The WILLOW Study With M5049 in SLE and CLE (SCLE and/or DLE) (WILLOW)
Systemic Lupus Erythematosus
Bottom Line
View on ClinicalTrials.gov: NCT05162586 ↗Enrolled (actual)
456
Serious AEs
3.5%
Results posted
Dec 2025
Primary outcome: Primary: Cohort A: Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index-A (CLASI-A) Total Score at Week 16 — -5.0; -9.0; -10.2; -9.7 scores on a scale
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Enpatoran low dose (Drug); Enpatoran medium dose (Drug); Enpatoran high dose (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- EMD Serono Research & Development Institute, Inc.
- Primary completion
- Nov 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cohort A: Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index-A (CLASI-A) Total Score at Week 16 |
-5.0; -9.0; -10.2; -9.7 | — |
| PRIMARY Cohort B: Number of Participants With British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response at Week 24 |
37; 41; 36; 56 | — |
| SECONDARY Cohort A and B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events (AEs) of Special Interest |
12; 15; 15; 21; 61; 42 | — |
| SECONDARY Cohort A and B: Number of Participants With Abnormal Laboratory Parameters |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort A and B: Number of Participants With Clinically Important Increases in QT Interval Corrected Using Fridericia's Formula (QTcF) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY 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 |
3.0; 3.0; 3.0; 3.179; 2.8; 2.9 | — |
| SECONDARY Cohort A and Cohort B: Change From Baseline in Physician's Global Assessment of Cutaneous Lupus Disease Activity Score at Week 16 and 24 |
61.4; 61.8; 56.3; 61.7; 55.7; 56.1 | — |
| SECONDARY Cohort B: Number of Participants With Both BICLA Response and With Clinically Meaningful Corticosteroids (CS) Reduction |
16; 20; 20; 28 | — |
| SECONDARY Cohort A and B: Number of Participants With Clinically Meaningful Corticosteroids (CS) Reduction |
6; 7; 12; 9; 36; 28 | — |
| SECONDARY Cohort A: Number of Participants With CLA-IGA Score 0 or 1 at Week 16 and Week 24 |
4; 10; 10; 12; 7; 11 | — |
| SECONDARY Cohort B: Number of Participants With Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24 |
50; 44; 48; 77 | — |
| SECONDARY Cohort B: Number of Participants With Lupus Low Disease Activity State (LLDAS) Attainment at Week 24 |
23; 21; 32; 35 | — |
| SECONDARY Cohort B: Number of Participants With Remission Attainment at Week 24 |
10; 7; 8; 20 | — |
| SECONDARY Cohort B: Percentage of Participants With 50% Reduction in Baseline Tender and Swollen Count at Week 24 |
68.8; 72.2; 77.6; 79.1 | — |
| SECONDARY Cohort B: Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare |
NA; NA; NA; NA | — |
| SECONDARY Cohort B: Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare |
NA; NA; NA; NA | — |
| SECONDARY Cohort A and B: Change From Baseline in Skindex 29+3 Symptom Domain Score at Week 24 |
-13.7; -27.3; -28.6; -21.9; -9.2; -17.5 | — |
| SECONDARY Cohort A and B: Change From Baseline in the Skindex 29+3 Functioning Domain Scores at Week 24 |
-12.2; -17.9; -20.3; -15.1; -11.1; -14.2 | — |
| SECONDARY Cohort A and B: Change From Baseline in the Skindex 29+3 Emotion Domain Scores at Week 24 |
-15.8; -23.1; -21.2; -23.2; -15.3; -18.0 | — |
| SECONDARY Cohort A and B: Change From Baseline in the Skindex 29+3 Lupus-Specific Domain Scores at Week 24 |
-15.5; -19.9; -21.1; -11.0; -16.4; -10.9 | — |
| SECONDARY Cohort A and B: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scores at Week 24 |
3.0; 2.0; 6.9; 4.3; 2.4; 4.8 | — |
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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT05162586). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.