The WILLOW Study With M5049 in SLE and CLE (SCLE and/or DLE) (WILLOW)

NCT ID: NCT05162586

Last Updated: 2025-12-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 456 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-31
• Study Completion Date: 2024-11-20

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.

Conditions

Systemic Lupus Erythematosus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive placebo matched to Enpatoran up to 24 weeks.

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.

Group Type: EXPERIMENTAL

Enpatoran low dose

Intervention Type: DRUG

Participants will receive film-coated tablets of Enpatoran at a low dose orally, twice daily (BID) up to 24 weeks.

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.

Group Type: EXPERIMENTAL

Enpatoran medium dose

Intervention Type: DRUG

Participants will receive film-coated tablets of Enpatoran at a medium dose, orally, BID up to 24 weeks.

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.

Group Type: EXPERIMENTAL

Enpatoran high dose

Intervention Type: DRUG

Participants will receive film-coated tablets of Enpatoran at a high dose, orally, BID up to 24 weeks.

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 .

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive placebo matched to Enpatoran up to 24 weeks.

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.

Group Type: EXPERIMENTAL

Enpatoran high dose

Intervention Type: DRUG

Participants will receive film-coated tablets of Enpatoran at a high dose, orally, BID up to 24 weeks.

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.

Group Type: EXPERIMENTAL

Enpatoran low dose

Intervention Type: DRUG

Participants will receive film-coated tablets of Enpatoran at a low dose orally, twice daily (BID) up to 24 weeks.

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.

Group Type: EXPERIMENTAL

Enpatoran medium dose

Intervention Type: DRUG

Participants will receive film-coated tablets of Enpatoran at a medium dose, orally, BID up to 24 weeks.

Interventions

Enpatoran low dose

Participants will receive film-coated tablets of Enpatoran at a low dose orally, twice daily (BID) up to 24 weeks.

Intervention Type: DRUG

Enpatoran medium dose

Participants will receive film-coated tablets of Enpatoran at a medium dose, orally, BID up to 24 weeks.

Intervention Type: DRUG

Enpatoran high dose

Participants will receive film-coated tablets of Enpatoran at a high dose, orally, BID up to 24 weeks.

Intervention Type: DRUG

Placebo

Participants will receive placebo matched to Enpatoran up to 24 weeks.

Intervention Type: DRUG

Other Intervention Names

M5049; M5049; M5049

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

EMD Serono Research & Development Institute, Inc.

Locations

The Lundquist Institute at Harbor-UCLA Medical Center

Torrance, California, United States

Bay Area Arthritis and Osteoporosis

Brandon, Florida, United States

Advance Medical Research Center

Miami, Florida, United States

New Horizon Research Center, Inc

Miami, Florida, United States

Charisma Medical and Research Center

Miami Lakes, 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

University of Minnesota

Minneapolis, Minnesota, United States

Across the Life Span

Smithfield, North Carolina, United States

Ohio State University - CTMO Parent

Columbus, Ohio, United States

Ramesh C Gupta, MD - Memphis, TN

Memphis, Tennessee, 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

Countries

United States; Argentina; Australia; Brazil; Bulgaria; Chile; China; Colombia; Greece; Israel; Japan; Mauritius; Mexico; Moldova; Philippines; Poland; Romania; Serbia; South Africa; South Korea; Spain; Taiwan

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS200569_0003

Trial Awareness and Transparency website

https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

2021-004648-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-510872-18-00

Identifier Type: CTIS

Identifier Source: secondary_id

MS200569_0003

Identifier Type: -

Identifier Source: org_study_id