The WILLOW Study With M5049 in SLE and CLE (SCLE and/or DLE) (WILLOW)
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)
3 other identifiers
interventional
456
22 countries
153
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Mar 2022
153 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 8, 2021
CompletedFirst Posted
Study publicly available on registry
December 17, 2021
CompletedStudy Start
First participant enrolled
March 31, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 20, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
November 20, 2024
CompletedResults Posted
Study results publicly available
December 1, 2025
CompletedDecember 1, 2025
November 1, 2025
2.6 years
December 8, 2021
November 17, 2025
November 17, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Cohort A: Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index-A (CLASI-A) Total Score at 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.
Baseline, week 16
Cohort B: Number of Participants With British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response 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.
At Week 24
Secondary Outcomes (19)
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
- +14 more secondary outcomes
Study Arms (8)
Cohort A: Placebo
PLACEBO COMPARATORParticipants 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 A: Enpatoran low dose
EXPERIMENTALParticipants 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 A: Enpatoran medium dose
EXPERIMENTALParticipants 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 A: Enpatoran high dose
EXPERIMENTALParticipants 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.
Cohort B (Part 1 + Part 2): Placebo
PLACEBO COMPARATORParticipants 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 1 + Part 2): Enpatoran high dose
EXPERIMENTALParticipants 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 B (Part 2): Enpatoran low dose
EXPERIMENTALParticipants 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 B (Part 2): Enpatoran medium dose
EXPERIMENTALParticipants 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.
Interventions
Participants will receive film-coated tablets of Enpatoran at a low dose orally, twice daily (BID) up to 24 weeks.
Participants will receive film-coated tablets of Enpatoran at a medium dose, orally, BID up to 24 weeks.
Participants will receive film-coated tablets of Enpatoran at a high dose, orally, BID up to 24 weeks.
Participants will receive placebo matched to Enpatoran up to 24 weeks.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (153)
The Lundquist Institute at Harbor-UCLA Medical Center
Torrance, California, 90509, United States
Bay Area Arthritis and Osteoporosis
Brandon, Florida, 33511, United States
Advance Medical Research Center
Miami, Florida, 33135, United States
New Horizon Research Center, Inc
Miami, Florida, 33165, United States
Charisma Medical and Research Center
Miami Lakes, Florida, 33014, United States
HMD Research, LLC
Orlando, Florida, 32819, United States
D&H Tamarac Research Center, LLC
Tamarac, Florida, 33321, United States
RNA America Health Sciences
Sugar Hill, Georgia, 30518, United States
Dawes Fretzin Dermatology Group, LLC
Indianapolis, Indiana, 46256, United States
AA MRC LLC Ahmed Arif Medical Research Center
Grand Blanc, Michigan, 48439, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Across the Life Span
Smithfield, North Carolina, 27577, United States
Ohio State University - CTMO Parent
Columbus, Ohio, 43215, United States
Ramesh C Gupta, MD - Memphis, TN
Memphis, Tennessee, 38119, United States
CINME - Centro De Investigaciones Metabolicas
Buenos Aires, Argentina
Buenos Aires Skin
Ciudad Autonoma Buenos Aires, Argentina
Centro Dermatologico Schejtman
Ciudad Autonoma Buenos Aires, Argentina
Hospital Militar Central Dr. Cosme Argerich
Ciudad Autonoma Buenos Aires, Argentina
Centro de Investigaciones Medicas Mar del Plata - CIM
Mar del Plata, Argentina
Instituto de Reumatologia
Mendoza, Argentina
Instituto Medico de la Fundacion Estudios Clinicos
Rosario, Argentina
Instituto Medico de alta Complejidad San Isidro S.A (IMAC)
San Fernando, Argentina
CER San Juan Centro Polivalente de Asistencia e Inv. Clinica
San Juan, Argentina
PSORIAHUE-Medicina Interdisciplinar
San Miguel, Argentina
Centro de Investigaciones Medicas Tucuman
San Miguel de Tucumán, Argentina
Investigaciones Clinicas Tucuman
San Miguel de Tucumán, Argentina
Monash Medical Centre Clayton
Clayton, Australia
Westmead Hospital - SUPERSEDED
Westmead, Australia
Veracity Clinical Research
Woolloongabba, Australia
Santa Casa de Misericórdia de Belo Horizonte
Belo Horizonte, Brazil
Oncovida - Centro de Onco-Hematologia de Mato Grosso
Cuiabá, Brazil
CETI - Centro de Estudos em Terapias Inovadoras Ltda.
Curitiba, Brazil
HUWC - UFC - Hospital Universitário Walter Cantídio - Universidade Federal do Ceará
Fortaleza, Brazil
CMiP - Centro Mineiro de Pesquisa
Juiz de Fora, Brazil
Hospital Bruno Born
Lajeado, Brazil
Hospital Moinhos de Vento
Porto Alegre, Brazil
Clínica SER da Bahia
Salvador, Brazil
Fundação Faculdade Regional de Medicina de São José do Rio Preto - CIP - Centro Integrado de Pesquisa
São José do Rio Preto, Brazil
CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos
São Paulo, Brazil
CPCLIN - Centro de Pesquisas Clínicas Ltda.
São Paulo, Brazil
DCC 'Sveti Georgi' EOOD - Cardiology Office
Haskovo, Bulgaria
MC Artmed OOD
Plovdiv, Bulgaria
Medical Center-1-Sevlievo EOOD
Sevlievo, Bulgaria
DCC "Alexandrovska", EOOD
Sofia, Bulgaria
Military Medical Academy - MHAT - Sofia - Department of Rheumatology
Sofia, Bulgaria
UMHAT "Sv. Ivan Rilski", EAD - Clinic of Rheumatology
Sofia, Bulgaria
Clínica Alemana de Osorno
Osorno, Chile
BioMedica Research Group - Psicomedica Clinical and Research Group
Santiago, Chile
CeCim Biocinetic
Santiago, Chile
Centro Medico Prosalud
Santiago, Chile
CIEC - Centro Internacional de Estudios Clínicos - Valenzuela Y Compania Ltda
Santiago, Chile
Dermacross
Santiago, Chile
The First Affiliated Hospital of Baotou Medical College
Baotou, China
Peking Union Medical College Hospital - Beijing Union Medical College Hospital
Beijing, China
The First Hospital of Jilin University
Changchun, China
The 2nd Xiangya Hospital of Central South University
Changsha, China
West China Hospital, Sichuan University
Chengdu, China
Guangdong Provincial People's Hospital - Oncology
Guangzhou, China
The First Affiliated Hospital, Sun Yat-sen University
Guangzhou, China
Hainan General Hospital
Haikou, China
The Affiliated Hospital of Inner Mongolia Medical University
Hohhot, China
The First Affiliated Hospital of Henan University of Science and Technology
Luoyang, China
The Second Affiliated Hospital of Nanchang University
Nanchang, China
Hospital for Skin Diseases, Chinese Academy of Medical Sciences
Nanjing, China
The Affiliated Drum Tower Hospital of Nanjing University
Nanjing, China
Huashan Hospital, Fudan University
Shanghai, China
Renji Hospital Shanghai Jiaotong University School of Medicine - West Branch
Shanghai, China
Ruijin Hospital of Shanghai Jiaotong University School of Medicine
Shanghai, China
Shanghai Skin Disease Hospital
Shanghai, China
The First Affiliated Hospital of Soochow University
Suzhou, China
Tianjin Medical University General Hospital
Tianjin, China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, China
Centro de Investigacion Medico Asistencial S.A.S
Barranquilla, Colombia
Centro de Investigacion en Reumatologia y Especialidades Medicas CIREEM S.A.S.
Bogotá, Colombia
Servimed S.A.S.
Bucaramanga, Colombia
Centro Integral de Reumatologia del Caribe SAS CIRCARIBE SAS
Medellín, Colombia
Healthy Medical Center
Zipaquirá, Colombia
"Andreas Syggros" Hospital - Department of Dermatology
Athens, Greece
General Hospital of Athens Laiko
Athens, Greece
University Hospital of Patra
Pátrai, Greece
General Hospital of Thessaloniki "Hippokration"
Thessaloniki, Greece
General Hospital Papageorgiou
Thessaloniki, Greece
Skin and Venereal Diseases' Hospital
Thessaloniki, Greece
Chaim Sheba Medical Center - pt
Ramat Gan, Israel
NHO Asahikawa Medical Center - Dept of Gastroenterology
Asahikawa-shi, Japan
NHO Chibahigashi National Hospital - Dept of Allergy/Rheumatology
Chiba, Japan
St. Luke's International Hospital - Dept of Immunology/Allergy
Chūōku, Japan
Hiroshima University Hospital - Dept of Rheumatology/Immunology
Hiroshima, Japan
Eiraku Clinic - Dept of Rheumatology
Kagoshima, Japan
Kanazawa University Hospital - Dept of Rheumatology/Immunology
Kanazawa, Japan
Saitama Medical Center - Dept of Rheumatology/Immunology
Kawagoe-shi, Japan
Kagawa University Hospital - Dept of Immunology/ Rheumatology
Kita-gun, Japan
Toho University Ohashi Medical Center - Dept of Immunology/Rheumatology
Meguro-ku, Japan
Hokkaido University Hospital - Dept of Internal Medicine 2(Rheumatology/Immunolog
Sapporo, Japan
Tohoku University Hospital - Dept of Hematology/Immunology
Sendai, Japan
Ehime University Hospital - Dept of Immunology/Rheumatology
Toon-shi, Japan
CAP Research Ltd
Quatre Bornes, Mauritius
Consultorio Particular del Dr. Miguel Cortes Hernandez - (dentro del Centro de Especialidades Medicas Vista
Cuernavaca, Mexico
Centro de Estudios de Investigacion Basica y Clinica SC
Guadalajara, Mexico
Centro Medico del Angel
Mexicali, Mexico
CAIMED Investigacion en salud S.A de C.V.
Mexico City, Mexico
Centro de Investigacion Clínica GRAMEL S.C
México, Mexico
Citer, Centro de Investigación Y Tratamiento de Las Enfermedades Reumaticas Sa de Cv
México, Mexico
Clinstile, S.A. de C.V.
México, Mexico
Consultorio de Reumatologia - Hospital Angeles Lindavista Cons. 445B
México, Mexico
Grupo Medico Camino S.C.
México, Mexico
CIMAB S.A. de C.V. - Centro de Investigacion Medica Alberto Bazzoni
Torreón, Mexico
Medical Care & Research SA de CV
Yucatán, Mexico
ICS ARENSIA Exploratory Medicine SRL - Republican Clinical Hospital "Timofei Mosneaga"
Chisinau, Moldova
Perpetual Succour Hospital
Cebu City, Philippines
Davao Doctors Hospital - Medicine
Davao City, Philippines
Iloilo Doctors Hospital
Iloilo City, Philippines
Mary Mediatrix Medical Center
Lipa City, Philippines
Chinese General Hospital & Medical Center
Manila, Philippines
Far Eastern University - Dr. Nicanor Reyes Medical Foundation - Department of Child Health
Quezon City, Philippines
Ospital Ng Makati
Quezon City, Philippines
Nova Reuma Spolka Partnerska
Bialystok, Poland
Prywatna Praktyka Lekarska prof Pawel Hrycaj
Kościan, Poland
Centrum Medyczne Plejady
Krakow, Poland
Centrum Nowoczesnych Terapii Dobry Lekarz
Krakow, Poland
Twoja Przychodnia Opolskie Centrum Medyczne
Opole, Poland
Twoja Przychodnia PCM
Poznan, Poland
Twoja Przychodnia-Szczecinskie Centrum Medyczne
Szczecin, Poland
Clinical Best Solutions - Warszawa
Warsaw, Poland
Centrul Medical Monza SRL - Arensia Exploratory Medicine
Bucharest, Romania
S.C Delta Health Care S.R.L - Ponderas Academic Hospital
Bucharest, Romania
Spitalul Clinic "Sf. Maria" - Clinica de Medicina Interna si Reumatologie
Bucharest, Romania
Spitalul Clinic "Sf. Maria" - parent
Bucharest, Romania
Spitalul Clinic Colentina - parent
Bucharest, Romania
Sc Medaudio-Optica SRL
Râmnicu Vâlcea, Romania
Institute of Rheumatology- 1
Belgrade, Serbia
Institute of Rheumatology-1
Belgrade, Serbia
Institute of Rheumatology
Belgrade, Serbia
University Clinical Center of Serbia - Clinic of Alergology and Imunology
Belgrade, Serbia
University Clinical Center Kragujevac
Kragujevac, Serbia
Arthritis Clinical Research Trial Unit - Dr CE Spargo and Dr RB Bhorat
Cape Town, South Africa
University of Pretoria Clinical Research Unit - Parent
Pretoria, South Africa
Naidoo, A - Netcare Umhlanga Hospital
Umhlanga, South Africa
Pusan National University Hospital
Busan, South Korea
Gachon University Gil Medical Center
Incheon, South Korea
Seoul National University Hospital
Seoul, South Korea
Ajou University Hospital
Suwon, South Korea
Complejo Hospitalario Universitario A Coruña - Servicio de Reumatologia
A Coruña, Spain
Hospital General de Castellon - Servicio de Reumatologia
Castelló, Spain
Hospital Universitario 12 de Octubre - Servicio de Reumatologia
Madrid, Spain
Hospital Regional Universitario de Malaga - Reumatology Dept
Málaga, Spain
Hospital Universitario Marques de Valdecilla - Servicio de Reumatologia
Santander, Spain
Hospital Quironsalud Sagrado Corazon - Reumatologia
Seville, Spain
Hospital Universitario Dr. Peset - Servicio de Reumatologia
Valencia, Spain
Hospital Universitario Rio Hortega - Servicio de Medicina Interna
Valladolid, Spain
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, Taiwan
Cheng Hsin General Hospital
Taipei, Taiwan
Taipei Veterans General Hospital
Taipei, Taiwan
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Communication Center
- Organization
- Merck Healthcare KGaA, DarmstadtGermany, an affiliate of Merck KGaA,Darmstadt, Germany
Study Officials
- STUDY DIRECTOR
Medical Responsible
EMD Serono Research & Development Institute, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 8, 2021
First Posted
December 17, 2021
Study Start
March 31, 2022
Primary Completion
November 20, 2024
Study Completion
November 20, 2024
Last Updated
December 1, 2025
Results First Posted
December 1, 2025
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
- Time Frame
- Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
- Access Criteria
- Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21