Clinical trial NCT05162586: The WILLOW Study With M5049 in SLE and CLE (SCLE and/or DLE) (WILLOW)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Keywords: Toll-like Receptor 7
Toll-like Receptor 8
WILLOW
Adults
SLE
CLE
Lupus
Discoid lupus erythematosus
Subacute cutaneous lupus erythematosus
M5049
Enpatoran
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2021-12-17
Enrollment: 456
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Cohort A: Percent Change from Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-A) at Week 16
timeFrame: Baseline, Week 16
measure: Cohort B: British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response at Week 24
timeFrame: At Week 24
Secondary outcomes:
measure: 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
timeFrame: Baseline (Day 1) up to End of Safety Follow-up Period (Week 33)
measure: Cohort A and Cohort B: Change from Baseline in Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) at Week 16 and Week 24
timeFrame: Baseline, Week 16 and 24
measure: Cohort A and Cohort B: Change from Baseline in Physician's Global Assessment of Cutaneous Lupus Disease Activity at Week 16 and 24
timeFrame: Baseline, Week 16 and 24
measure: Cohort B: Participants with British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response and with Clinically Meaningful Corticosteroids (CS) Reduction
timeFrame: Day 1 up to Week 24
measure: Cohort A: Clinically Meaningful Corticosteroids (CS) Reduction
timeFrame: Day 1 up to Week 24
measure: Cohort A: Ocurrence of Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) Score 0 or 1 at Week 16 and Week 24
timeFrame: At Week 16 and 24
measure: Cohort B: Systemic lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24
timeFrame: At Week 24
measure: Cohort B: Lupus Low Disease Activity State (LLDAS) Attainment at Week 24
timeFrame: At Week 24
measure: Cohort B: Remission Attainment at Week 24
timeFrame: At Week 24
measure: Cohort B: Change From Baseline in Tender Joint Count and Swollen Joint Count at Week 24
timeFrame: Baseline, Week 24
measure: Cohort B: Change from Baseline in Physician's Global Assessment at Week 24
timeFrame: Baseline, Week 24
measure: Cohort B: Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare
timeFrame: Day 1 through Week 24
measure: Cohort B: Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare
timeFrame: Day 1 through Week 24
measure: Cohort A and B: Change from Baseline in Skindex 29+3 Symptom Domain Score at Week 24
timeFrame: Baseline, Week 24
measure: Cohort A and B: Change from Baseline in the Skindex 29+3 Functioning and Emotion Domain Scores at Week 24
timeFrame: Baseline, Week 24
measure: Change from Baseline in the Skindex 29+3 Lupus-Specific Domain Score at Week 24
timeFrame: Baseline, Week 24
measure: Cohort A and B: Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scores at Week 24
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Torrance
country: United States
facility: The Lundquist Institute at Harbor-UCLA Medical Center
state: California
city: Brandon
country: United States
facility: Bay Area Arthritis and Osteoporosis
state: Florida
city: Miami Lakes
country: United States
facility: Charisma Medical and Research Center
state: Florida
city: Miami
country: United States
facility: Advance Medical Research Center
state: Florida
city: Miami
country: United States
facility: New Horizon Research Center, Inc
state: Florida
city: Orlando
country: United States
facility: HMD Research, LLC
state: Florida
city: Tamarac
country: United States
facility: D&H Tamarac Research Center, LLC
state: Florida
city: Sugar Hill
country: United States
facility: RNA America Health Sciences
state: Georgia
city: Indianapolis
country: United States
facility: Dawes Fretzin Dermatology Group, LLC
state: Indiana
city: Grand Blanc
country: United States
facility: AA MRC LLC Ahmed Arif Medical Research Center
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Smithfield
country: United States
facility: Across the Life Span
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University - CTMO Parent
state: Ohio
city: Memphis
country: United States
facility: Ramesh C Gupta, MD - Memphis, TN
state: Tennessee
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Buenos Aires Skin
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Centro Dermatologico Schejtman
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital Militar Central Dr. Cosme Argerich
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: CINME - Centro De Investigaciones Metabolicas
city: Mar del Plata
country: Argentina
facility: Centro de Investigaciones Medicas Mar del Plata - CIM
city: Mendoza
country: Argentina
facility: Instituto de Reumatologia
city: Rosario
country: Argentina
facility: Instituto Medico de la Fundacion Estudios Clinicos
city: San Fernando
country: Argentina
facility: Instituto Medico de alta Complejidad San Isidro S.A (IMAC)
city: San Juan
country: Argentina
facility: CER San Juan Centro Polivalente de Asistencia e Inv. Clinica
city: San Miguel de Tucuman
country: Argentina
facility: Investigaciones Clinicas Tucuman
city: San Miguel
country: Argentina
facility: PSORIAHUE-Medicina Interdisciplinar
city: Tucuman
country: Argentina
facility: Centro de Investigaciones Medicas Tucuman
city: Clayton
country: Australia
facility: Monash Medical Centre Clayton
city: Westmead
country: Australia
facility: Westmead Hospital - SUPERSEDED
city: Woolloongabba
country: Australia
facility: Veracity Clinical Research
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericórdia de Belo Horizonte
city: Cuiabá
country: Brazil
facility: Oncovida - Centro de Onco-Hematologia de Mato Grosso
city: Curitiba
country: Brazil
facility: CETI - Centro de Estudos em Terapias Inovadoras Ltda.
city: Fortaleza
country: Brazil
facility: HUWC - UFC - Hospital Universitário Walter Cantídio - Universidade Federal do Ceará
city: Juiz de Fora
country: Brazil
facility: CMiP - Centro Mineiro de Pesquisa
city: Lajeado
country: Brazil
facility: Hospital Bruno Born
city: Porto Alegre
country: Brazil
facility: Hospital Moinhos de Vento
city: Salvador
country: Brazil
facility: Clínica SER da Bahia
city: Sao Jose do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto - CIP - Centro Integrado de Pesquisa
city: Sao Paulo
country: Brazil
facility: CPCLIN - Centro de Pesquisas Clínicas Ltda.
city: São Paulo
country: Brazil
facility: CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos
city: Haskovo
country: Bulgaria
facility: DCC 'Sveti Georgi' EOOD - Cardiology Office
city: Plovdiv
country: Bulgaria
facility: MC Artmed OOD
city: Sevlievo
country: Bulgaria
facility: Medical Center-1-Sevlievo EOOD
city: Sofia
country: Bulgaria
facility: DCC "Alexandrovska", EOOD
city: Sofia
country: Bulgaria
facility: Military Medical Academy - MHAT - Sofia - Department of Rheumatology
city: Sofia
country: Bulgaria
facility: UMHAT "Sv. Ivan Rilski", EAD - Clinic of Rheumatology
city: Osorno
country: Chile
facility: Clínica Alemana de Osorno
city: Santiago
country: Chile
facility: BioMedica Research Group - Psicomedica Clinical and Research Group
city: Santiago
country: Chile
facility: CeCim Biocinetic
city: Santiago
country: Chile
facility: Centro Medico Prosalud
city: Santiago
country: Chile
facility: CIEC - Centro Internacional de Estudios Clínicos - Valenzuela Y Compania Ltda
city: Santiago
country: Chile
facility: Dermacross
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College
city: Beijing
country: China
facility: Peking Union Medical College Hospital - Beijing Union Medical College Hospital
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Changsha
country: China
facility: The 2nd Xiangya Hospital of Central South University
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital - Oncology
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
city: Haikou
country: China
facility: Hainan General Hospital
city: Hohhot
country: China
facility: The Affiliated Hospital of Inner Mongolia Medical University
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
city: Nanjing
country: China
facility: Hospital for Skin Diseases, Chinese Academy of Medical Sciences
city: Nanjing
country: China
facility: The Affiliated Drum Tower Hospital of Nanjing University
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
city: Shanghai
country: China
facility: Renji Hospital Shanghai Jiaotong University School of Medicine - West Branch
city: Shanghai
country: China
facility: Ruijin Hospital of Shanghai Jiaotong University School of Medicine
city: Shanghai
country: China
facility: Shanghai Skin Disease Hospital
city: SuZhou
country: China
facility: The First Affiliated Hospital of Soochow University
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
city: Barranquilla
country: Colombia
facility: Centro de Investigacion Medico Asistencial S.A.S
city: Bogotá
country: Colombia
facility: Centro de Investigacion en Reumatologia y Especialidades Medicas CIREEM S.A.S.
city: Bucaramanga
country: Colombia
facility: Servimed S.A.S.
city: Medellin
country: Colombia
facility: Centro Integral de Reumatologia del Caribe SAS CIRCARIBE SAS
city: Zipaquirá
country: Colombia
facility: Healthy Medical Center
city: Athens
country: Greece
facility: "Andreas Syggros" Hospital - Department of Dermatology
city: Athens
country: Greece
facility: General Hospital of Athens Laiko
city: Patra
country: Greece
facility: University Hospital of Patra
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki "Hippokration"
city: Thessaloniki
country: Greece
facility: General Hospital Papageorgiou
city: Thessaloniki
country: Greece
facility: Skin and Venereal Diseases' Hospital
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center - pt
city: Asahikawa-shi
country: Japan
facility: NHO Asahikawa Medical Center - Dept of Gastroenterology
city: Chiba-shi
country: Japan
facility: NHO Chibahigashi National Hospital - Dept of Allergy/Rheumatology
city: Chuo-ku
country: Japan
facility: St. Luke's International Hospital - Dept of Immunology/Allergy
city: Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital - Dept of Rheumatology/Immunology
city: Kagoshima-shi
country: Japan
facility: Eiraku Clinic - Dept of Rheumatology
city: Kanazawa-shi
country: Japan
facility: Kanazawa University Hospital - Dept of Rheumatology/Immunology
city: Kawagoe-shi
country: Japan
facility: Saitama Medical Center - Dept of Rheumatology/Immunology
city: Kita-gun
country: Japan
facility: Kagawa University Hospital - Dept of Immunology/ Rheumatology
city: Meguro-ku
country: Japan
facility: Toho University Ohashi Medical Center - Dept of Immunology/Rheumatology
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital - Dept of Internal Medicine 2(Rheumatology/Immunolog
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital - Dept of Hematology/Immunology
city: Toon-shi
country: Japan
facility: Ehime University Hospital - Dept of Immunology/Rheumatology
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Quatre Bornes
country: Mauritius
facility: CAP Research Ltd
city: Ciudad de México
country: Mexico
facility: CAIMED Investigacion en salud S.A de C.V.
city: Cuernavaca
country: Mexico
facility: Consultorio Particular del Dr. Miguel Cortes Hernandez - (dentro del Centro de Especialidades Medicas Vista
city: Guadalajara
country: Mexico
facility: Centro de Estudios de Investigacion Basica y Clinica SC
city: Mexicali
country: Mexico
facility: Centro Medico del Angel
city: Mexico
country: Mexico
facility: Centro de Investigacion Clínica GRAMEL S.C
city: Mexico
country: Mexico
facility: Citer, Centro de Investigación Y Tratamiento de Las Enfermedades Reumaticas Sa de Cv
city: Mexico
country: Mexico
facility: Clinstile, S.A. de C.V.
city: Mexico
country: Mexico
facility: Consultorio de Reumatologia - Hospital Angeles Lindavista Cons. 445B
city: Mexico
country: Mexico
facility: Grupo Medico Camino S.C.
city: Torreon
country: Mexico
facility: CIMAB S.A. de C.V. - Centro de Investigacion Medica Alberto Bazzoni
city: Yucatan
country: Mexico
facility: Medical Care & Research SA de CV
city: Chisinau
country: Moldova, Republic of
facility: ICS ARENSIA Exploratory Medicine SRL - Republican Clinical Hospital "Timofei Mosneaga"
city: Cebu City
country: Philippines
facility: Perpetual Succour Hospital
city: Davao City
country: Philippines
facility: Davao Doctors Hospital - Medicine
city: Iloilo City
country: Philippines
facility: Iloilo Doctors Hospital
city: Lipa City
country: Philippines
facility: Mary Mediatrix Medical Center
city: Manila
country: Philippines
facility: Chinese General Hospital & Medical Center
city: Quezon City
country: Philippines
facility: Far Eastern University - Dr. Nicanor Reyes Medical Foundation - Department of Child Health
city: Quezon City
country: Philippines
facility: Ospital Ng Makati
city: Bialystok
country: Poland
facility: Nova Reuma Spolka Partnerska
city: Koscian
country: Poland
facility: Prywatna Praktyka Lekarska prof Pawel Hrycaj
city: Krakow
country: Poland
facility: Centrum Medyczne Plejady
city: Krakow
country: Poland
facility: Centrum Nowoczesnych Terapii Dobry Lekarz
city: Opole
country: Poland
facility: Twoja Przychodnia Opolskie Centrum Medyczne
city: Poznan
country: Poland
facility: Twoja Przychodnia PCM
city: Szczecin
country: Poland
facility: Twoja Przychodnia-Szczecinskie Centrum Medyczne
city: Warszawa
country: Poland
facility: Clinical Best Solutions - Warszawa
city: Bucharest
country: Romania
facility: Centrul Medical Monza SRL - Arensia Exploratory Medicine
city: Bucuresti
country: Romania
facility: S.C Delta Health Care S.R.L - Ponderas Academic Hospital
city: Bucuresti
country: Romania
facility: Spitalul Clinic "Sf. Maria" - Clinica de Medicina Interna si Reumatologie
city: Bucuresti
country: Romania
facility: Spitalul Clinic "Sf. Maria" - parent
city: Bucuresti
country: Romania
facility: Spitalul Clinic Colentina - parent
city: Ramnicu Valcea
country: Romania
facility: Sc Medaudio-Optica SRL
city: Belgrade
country: Serbia
facility: Institute of Rheumatology- 1
city: Belgrade
country: Serbia
facility: Institute of Rheumatology-1
city: Belgrade
country: Serbia
facility: Institute of Rheumatology
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia - Clinic of Alergology and Imunology
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: Cape Town
country: South Africa
facility: Arthritis Clinical Research Trial Unit - Dr CE Spargo and Dr RB Bhorat
city: Pretoria
country: South Africa
facility: University of Pretoria Clinical Research Unit - Parent
city: Umhlanga
country: South Africa
facility: Naidoo, A - Netcare Umhlanga Hospital
city: Castelló
country: Spain
facility: Hospital General de Castellon - Servicio de Reumatologia
city: La Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña - Servicio de Reumatologia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre - Servicio de Reumatologia
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga - Reumatology Dept
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla - Servicio de Reumatologia
city: Sevilla
country: Spain
facility: Hospital Quironsalud Sagrado Corazon - Reumatologia
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset - Servicio de Reumatologia
city: Valladolid
country: Spain
facility: Hospital Universitario Rio Hortega - Servicio de Medicina Interna
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Cheng Hsin General Hospital
Study officials:
affiliation: EMD Serono Research & Development Institute, Inc.
name: Medical Responsible
role: STUDY_DIRECTOR
References: