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 dose; Drug: Enpatoran high dose; Drug: Enpatoran low dose; Drug: Placebo

• Registration Number: NCT05162586
• Lead Sponsor: EMD Serono Research & Development Institute, Inc.

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

Study Timeline

• Study First Submitted: 2021-12-08
• Study First Submitted QC: 2021-12-08
• Study First Posted: 2021-12-17
• Study Start: 2022-03-31
• Primary Completion: 2024-11-20
• Study Completion: 2024-11-20
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-03
• Last Update Posted: 2024-12-05

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

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

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

Buenos Aires Skin; 🇦🇷 Ciudad Autonoma Buenos Aires, Argentina

Instituto de Reumatologia; 🇦🇷 Mendoza, Argentina

Instituto Medico de la Fundacion Estudios Clinicos; 🇦🇷 Rosario, Argentina

Centro Dermatologico Schejtman; 🇦🇷 Ciudad Autonoma Buenos Aires, Argentina

Hospital Militar Central Dr. Cosme Argerich; 🇦🇷 Ciudad Autonoma Buenos Aires, Argentina

CINME - Centro De Investigaciones Metabolicas; 🇦🇷 Ciudad Autonoma de Buenos Aires, Argentina

Centro de Investigaciones Medicas Mar del Plata - CIM; 🇦🇷 Mar del Plata, 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

Investigaciones Clinicas Tucuman; 🇦🇷 San Miguel de Tucuman, Argentina

PSORIAHUE-Medicina Interdisciplinar; 🇦🇷 San Miguel, Argentina

Centro de Investigaciones Medicas Tucuman; 🇦🇷 Tucuman, Argentina

Veracity Clinical Research; 🇦🇺 Woolloongabba, Australia

Santa Casa de Misericórdia de Belo Horizonte; 🇧🇷 Belo Horizonte, Brazil

Monash Medical Centre Clayton; 🇦🇺 Clayton, Australia

Westmead Hospital - SUPERSEDED; 🇦🇺 Westmead, Australia

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

Fundação Faculdade Regional de Medicina de São José do Rio Preto - CIP - Centro Integrado de Pesquisa; 🇧🇷 Sao Jose do Rio Preto, Brazil

CPCLIN - Centro de Pesquisas Clínicas Ltda.; 🇧🇷 Sao Paulo, Brazil

CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos; 🇧🇷 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

Hospital Bruno Born; 🇧🇷 Lajeado, Brazil

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; 🇨🇴 Medellin, 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; 🇬🇷 Patra, 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-shi, Japan

Hospital Moinhos de Vento; 🇧🇷 Porto Alegre, Brazil

St. Luke's International Hospital - Dept of Immunology/Allergy; 🇯🇵 Chuo-ku, Japan

Hiroshima University Hospital - Dept of Rheumatology/Immunology; 🇯🇵 Hiroshima-shi, Japan

Eiraku Clinic - Dept of Rheumatology; 🇯🇵 Kagoshima-shi, Japan

Kanazawa University Hospital - Dept of Rheumatology/Immunology; 🇯🇵 Kanazawa-shi, 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-shi, Japan

Tohoku University Hospital - Dept of Hematology/Immunology; 🇯🇵 Sendai-shi, Japan

Ehime University Hospital - Dept of Immunology/Rheumatology; 🇯🇵 Toon-shi, Japan

Pusan National University Hospital; 🇰🇷 Busan, Korea, Republic of

Gachon University Gil Medical Center; 🇰🇷 Incheon, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Ajou University Hospital; 🇰🇷 Suwon, Korea, Republic of

CAP Research Ltd; 🇲🇺 Quatre Bornes, Mauritius

CAIMED Investigacion en salud S.A de C.V.; 🇲🇽 Ciudad de México, Mexico

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

Centro de Investigacion Clínica GRAMEL S.C; 🇲🇽 Mexico, Mexico

Citer, Centro de Investigación Y Tratamiento de Las Enfermedades Reumaticas Sa de Cv; 🇲🇽 Mexico, Mexico

Clinstile, S.A. de C.V.; 🇲🇽 Mexico, Mexico

Consultorio de Reumatologia - Hospital Angeles Lindavista Cons. 445B; 🇲🇽 Mexico, Mexico

Grupo Medico Camino S.C.; 🇲🇽 Mexico, Mexico

CIMAB S.A. de C.V. - Centro de Investigacion Medica Alberto Bazzoni; 🇲🇽 Torreon, Mexico

Medical Care & Research SA de CV; 🇲🇽 Yucatan, Mexico

ICS ARENSIA Exploratory Medicine SRL - Republican Clinical Hospital "Timofei Mosneaga"; 🇲🇩 Chisinau, Moldova, Republic of

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; 🇵🇱 Koscian, 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

Clínica SER da Bahia; 🇧🇷 Salvador, Brazil

Twoja Przychodnia-Szczecinskie Centrum Medyczne; 🇵🇱 Szczecin, Poland

Clinical Best Solutions - Warszawa; 🇵🇱 Warszawa, Poland

Centrul Medical Monza SRL - Arensia Exploratory Medicine; 🇷🇴 Bucharest, Romania

S.C Delta Health Care S.R.L - Ponderas Academic Hospital; 🇷🇴 Bucuresti, Romania

Spitalul Clinic "Sf. Maria" - Clinica de Medicina Interna si Reumatologie; 🇷🇴 Bucuresti, Romania

Spitalul Clinic "Sf. Maria" - parent; 🇷🇴 Bucuresti, Romania

Spitalul Clinic Colentina - parent; 🇷🇴 Bucuresti, Romania

Sc Medaudio-Optica SRL; 🇷🇴 Ramnicu Valcea, 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

Hospital Universitario 12 de Octubre - Servicio de Reumatologia; 🇪🇸 Madrid, Spain

Hospital Universitario Marques de Valdecilla - Servicio de Reumatologia; 🇪🇸 Santander, Spain

Naidoo, A - Netcare Umhlanga Hospital; 🇿🇦 Umhlanga, South Africa

Hospital General de Castellon - Servicio de Reumatologia; 🇪🇸 Castelló, Spain

Hospital Regional Universitario de Malaga - Reumatology Dept; 🇪🇸 Málaga, Spain

Complejo Hospitalario Universitario A Coruña - Servicio de Reumatologia; 🇪🇸 La Coruña, Spain

Hospital Universitario Rio Hortega - Servicio de Medicina Interna; 🇪🇸 Valladolid, Spain

Hospital Quironsalud Sagrado Corazon - Reumatologia; 🇪🇸 Sevilla, Spain

Hospital Universitario Dr. Peset - Servicio de Reumatologia; 🇪🇸 Valencia, Spain

Kaohsiung Chang Gung Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei City, Taiwan

Cheng Hsin General Hospital; 🇨🇳 Taipei, Taiwan