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

Systemic Lupus Erythematosus Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05162586
• Other study ID #: MS200569_0003
• Secondary ID: 2021-004648-27
• Status: Recruiting
• Phase: Phase 2
• Start date: March 31, 2022
• Est. completion date: August 16, 2024

Study information

• Verified date: February 2024
• Source: EMD Serono
• Contact: US Medical Information
• Phone: 888-275-7376
• Email: eMediUSA[@]emdserono.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 532
• Est. completion date: August 16, 2024
• Est. primary completion date: July 8, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• Enpatoran low dose
Participants will receive film-coated tablets of Enpatoran at a low dose orally, twice daily (BID) up to 24 weeks.
• Enpatoran medium dose
Participants will receive film-coated tablets of Enpatoran at a medium dose, orally, BID up to 24 weeks.
• Enpatoran high dose
Participants will receive film-coated tablets of Enpatoran at a high dose, orally, BID up to 24 weeks.
• Placebo
Participants will receive placebo matched to Enpatoran up to 24 weeks.

Locations

Country	Name	City	State
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	CINME - Centro De Investigaciones Metabolicas	Ciudad Autonoma de 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	Cordis S.A.	Salta
Argentina	Investigaciones Clínicas Salta (ICSAL)	Salta
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	Investigaciones Clinicas Tucuman	San Miguel de Tucuman
Argentina	Centro de Investigaciones Medicas Tucuman	Tucuman
Australia	Box Hill Hospital - PARENT	Caulfield
Australia	Monash Medical Centre Clayton	Clayton
Australia	Fiona Stanley Hospital - Haematology	Murdoch
Australia	Royal Melbourne Hospital - PARENT	Parkville
Australia	Westmead Hospital - SUPERSEDED	Westmead
Australia	Veracity Clinical Research	Woolloongabba
Brazil	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	Edumed - Educação e Saúde SA	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	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
Bulgaria	DCC 'Sveti Georgi' EOOD - Cardiology Office	Haskovo
Bulgaria	Medical center Medconsult Pleven OOD	Pleven
Bulgaria	MC Artmed OOD	Plovdiv
Bulgaria	DCC 1 - Ruse, EOOD	Ruse
Bulgaria	Medical Center-1-Sevlievo EOOD	Sevlievo
Bulgaria	DCC "Alexandrovska", EOOD	Sofia
Bulgaria	DCC Focus 5 - MEOH OOD	Sofia
Bulgaria	Military Medical Academy - MHAT - Sofia - Department of Rheumatology	Sofia
Bulgaria	UMHAT "Sv. Ivan Rilski", EAD - Clinic of Rheumatology	Sofia
Bulgaria	UMHAT Prof. Dr. Stoyan Kirkovich AD	Stara Zagora
Chile	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
China	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
Colombia	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
Greece	"Andreas Syggros" Hospital - Department of Dermatology	Athens
Greece	General Hospital of Athens Laiko	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
Israel	Chaim Sheba Medical Center - pt	Ramat Gan
Japan	NHO Asahikawa Medical Center - Dept of Gastroenterology	Asahikawa-shi
Japan	NHO Chibahigashi National Hospital - Dept of Allergy/Rheumatology	Chiba-shi
Japan	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
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Kyung Hee University Hospital at Gangdong:	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon
Mauritius	CAP Research Ltd	Quatre Bornes
Mexico	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	Consultorio Médico del Dr. Federico Galván Villegas	Guadalajara
Mexico	Diseño y Planeacion en Investigacion Medica S.C.	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	AMAF Clinical Research S.C	México
Mexico	Centro Regiomontano de Estudios Clínicos Roma S.C.	Monterrey
Mexico	CIMAB S.A. de C.V. - Centro de Investigacion Medica Alberto Bazzoni	Torreon
Mexico	Medical Care & Research SA de CV	Yucatan
Moldova, Republic of	ICS ARENSIA Exploratory Medicine SRL - Republican Clinical Hospital "Timofei Mosneaga"	Chisinau
Philippines	Green City Medical Center	Angeles City
Philippines	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
Poland	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	Twoja Przychodnia-Szczecinskie Centrum Medyczne	Szczecin
Poland	Clinical Best Solutions - Warszawa	Warszawa
Romania	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
Serbia	Institute of Rheumatology	Belgrade
Serbia	Institute of Rheumatology- 1	Belgrade
Serbia	Institute of Rheumatology-1	Belgrade
Serbia	University Clinical Center of Serbia - Clinic of Alergology and Imunology	Belgrade
Serbia	University Clinical Center Kragujevac	Kragujevac
South Africa	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
Spain	Hospital General de Castellon - Servicio de Reumatologia	Castelló
Spain	Complejo Hospitalario Universitario A Coruña - Servicio de Reumatologia	La Coruña
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	Sevilla
Spain	Hospital Universitario Dr. Peset - Servicio de Reumatologia	Valencia
Spain	Hospital Universitario Rio Hortega - Servicio de Medicina Interna	Valladolid
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	Cheng Hsin General Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei City
United States	Austin Regional Clinic, P.A.	Austin	Texas
United States	Bay Area Arthritis and Osteoporosis	Brandon	Florida
United States	Precision Comprehensive Clinical Research Solutions	Colleyville	Texas
United States	Ohio State University - CTMO Parent	Columbus	Ohio
United States	AA MRC LLC Ahmed Arif Medical Research Center	Grand Blanc	Michigan
United States	Dawes Fretzin Dermatology Group, LLC	Indianapolis	Indiana
United States	Ramesh C Gupta, MD - Memphis, TN	Memphis	Tennessee
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	University of Minnesota	Minneapolis	Minnesota
United States	HMD Research, LLC	Orlando	Florida
United States	Across the Life Span	Smithfield	North Carolina
United States	Jordan Valley Dermatology Center	South Jordan	Utah
United States	RNA America Health Sciences	Sugar Hill	Georgia
United States	D&H Tamarac Research Center, LLC	Tamarac	Florida
United States	Model Research Center, LLC	Tampa	Florida
United States	University of Toledo - PARENT	Toledo	Ohio
United States	The Lundquist Institute at Harbor-UCLA Medical Center	Torrance	California
United States	Rheumatology & Osteoporosis Institute of Oklahoma	Tulsa	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort A: Percent Change from Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-A) at Week 16		Baseline, Week 16
Primary	Cohort B: British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response at Week 24		At Week 24
Secondary	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)
Secondary	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
Secondary	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
Secondary	Cohort B: Participants with British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response and with Clinically Meaningful Corticosteroids (CS) Reduction	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.	Day 1 up to Week 24
Secondary	Cohort A: Clinically Meaningful Corticosteroids (CS) Reduction	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.	Day 1 up to Week 24
Secondary	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
Secondary	Cohort B: Systemic lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24		At Week 24
Secondary	Cohort B: Lupus Low Disease Activity State (LLDAS) Attainment at Week 24		At Week 24
Secondary	Cohort B: Remission Attainment at Week 24		At Week 24
Secondary	Cohort B: Change From Baseline in Tender Joint Count and Swollen Joint Count at Week 24		Baseline, Week 24
Secondary	Cohort B: Change from Baseline in Physician's Global Assessment at Week 24		Baseline, Week 24
Secondary	Cohort B: Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare		Day 1 through Week 24
Secondary	Cohort B: Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare		Day 1 through Week 24
Secondary	Cohort A and B: Change from Baseline in Skindex 29+3 Symptom Domain Score at Week 24		Baseline, Week 24
Secondary	Cohort A and B: Change from Baseline in the Skindex 29+3 Functioning and Emotion Domain Scores at Week 24		Baseline, Week 24
Secondary	Change from Baseline in the Skindex 29+3 Lupus-Specific Domain Score at Week 24		Baseline, Week 24
Secondary	Cohort A and B: Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scores at Week 24		Baseline, Week 24

External Links

•   Trial Awareness and Transparency website