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)

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.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Placebo; Drug: Enpatoran low dose; Drug: Enpatoran medium dose; Drug: Enpatoran high dose

• Study Type: Interventional
• Enrollment (Actual): 456
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • CINME - Centro de Investigaciones Metabolicas
  • Ciudad Autonoma 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
  • Mar del Plata, Argentina
    • Centro de Investigaciones Medicas Mar del Plata - CIM
  • Mendoza, Argentina
    • Instituto de Reumatologia
  • Rosario, Argentina
    • Instituto Medico de La Fundacion Estudios Clinicos
  • San Fernando, Argentina
    • Instituto Medico de alta Complejidad San Isidro S.A (IMAC)
  • San Juan, Argentina
    • CER San Juan Centro Polivalente de Asistencia e Inv. Clinica
  • San Miguel, Argentina
    • PSORIAHUE-Medicina Interdisciplinar
  • San Miguel de Tucumán, Argentina
    • Centro de Investigaciones Medicas Tucuman
  • San Miguel de Tucumán, Argentina
    • Investigaciones Clinicas Tucuman
• Australia
  • Clayton, Australia
    • Monash Medical Centre Clayton
  • Westmead, Australia
    • Westmead Hospital - SUPERSEDED
  • Woolloongabba, Australia
    • Veracity Clinical Research
• Brazil
  • Belo Horizonte, Brazil
    • Santa Casa de Misericordia de Belo Horizonte
  • Cuiabá, Brazil
    • Oncovida - Centro de Onco-Hematologia de Mato Grosso
  • Curitiba, Brazil
    • CETI - Centro de Estudos em Terapias Inovadoras Ltda.
  • Fortaleza, Brazil
    • HUWC - UFC - Hospital Universitário Walter Cantídio - Universidade Federal do Ceará
  • Juiz de Fora, Brazil
    • CMiP - Centro Mineiro de Pesquisa
  • Lajeado, Brazil
    • Hospital Bruno Born
  • Porto Alegre, Brazil
    • Hospital Moinhos de Vento
  • Salvador, Brazil
    • Clínica SER da Bahia
  • São José do Rio Preto, Brazil
    • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto - CIP - Centro Integrado de Pesquisa
  • São Paulo, Brazil
    • CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos
  • São Paulo, Brazil
    • CPCLIN - Centro de Pesquisas Clínicas Ltda.
• Bulgaria
  • Haskovo, Bulgaria
    • DCC 'Sveti Georgi' EOOD - Cardiology Office
  • Plovdiv, Bulgaria
    • MC Artmed OOD
  • Sevlievo, Bulgaria
    • Medical Center-1-Sevlievo EOOD
  • Sofia, Bulgaria
    • DCC "Alexandrovska", EOOD
  • Sofia, Bulgaria
    • Military Medical Academy - MHAT - Sofia - Department of Rheumatology
  • Sofia, Bulgaria
    • UMHAT "Sv. Ivan Rilski", EAD - Clinic of Rheumatology
• Chile
  • Osorno, Chile
    • Clinica Alemana de Osorno
  • Santiago, Chile
    • Centro Medico Prosalud
  • Santiago, Chile
    • BioMedica Research Group - Psicomedica Clinical and Research Group
  • Santiago, Chile
    • CeCim Biocinetic
  • Santiago, Chile
    • CIEC - Centro Internacional de Estudios Clínicos - Valenzuela Y Compania Ltda
  • Santiago, Chile
    • Dermacross
• China
  • Baotou, China
    • The First Affiliated Hospital of Baotou Medical College
  • Beijing, China
    • Peking Union Medical College Hospital - Beijing Union Medical College Hospital
  • Changchun, China
    • The First Hospital of Jilin University
  • Changsha, China
    • The 2nd Xiangya Hospital of Central South University
  • Chengdu, China
    • West China Hospital, Sichuan University
  • Guangzhou, China
    • The First Affiliated Hospital, Sun Yat-sen University
  • Guangzhou, China
    • Guangdong Provincial People's Hospital - Oncology
  • Haikou, China
    • Hainan General Hospital
  • Hohhot, China
    • The Affiliated Hospital of Inner Mongolia Medical University
  • Luoyang, China
    • The first affiliated hospital of Henan University of science and technology
  • Nanchang, China
    • The Second Affiliated Hospital of Nanchang University
  • Nanjing, China
    • Hospital for Skin Diseases, Chinese Academy of Medical Sciences
  • Nanjing, China
    • The Affiliated Drum Tower Hospital of Nanjing University
  • Shanghai, China
    • Shanghai skin disease hospital
  • Shanghai, 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
  • Suzhou, China
    • The First Affiliated Hospital of Soochow University
  • Tianjin, China
    • Tianjin Medical University General Hospital
  • Xi'an, China
    • The First Affiliated Hospital of Xi'an Jiaotong University
• Colombia
  • Barranquilla, Colombia
    • Centro de Investigacion Medico Asistencial S.A.S
  • Bogotá, Colombia
    • Centro de Investigacion en Reumatologia y Especialidades Medicas CIREEM S.A.S.
  • Bucaramanga, Colombia
    • Servimed S.A.S.
  • Medellín, Colombia
    • Centro Integral de Reumatologia del Caribe SAS CIRCARIBE SAS
  • Zipaquirá, Colombia
    • Healthy Medical Center
• Greece
  • Athens, Greece
    • General Hospital of Athens Laiko
  • Athens, Greece
    • "Andreas Syggros" Hospital - Department of Dermatology
  • Pátrai, Greece
    • University Hospital of Patra
  • Thessaloniki, Greece
    • General Hospital of Thessaloniki "Hippokration"
  • Thessaloniki, Greece
    • General Hospital Papageorgiou
  • Thessaloniki, Greece
    • Skin and Venereal Diseases' Hospital
• Israel
  • Ramat Gan, Israel
    • Chaim Sheba Medical Center - pt
• Japan
  • Asahikawa-shi, Japan
    • NHO Asahikawa Medical Center - Dept of Gastroenterology
  • Chiba, Japan
    • NHO Chibahigashi National Hospital - Dept of Allergy/Rheumatology
  • Chūōku, Japan
    • St. Luke's International Hospital - Dept of Immunology/Allergy
  • Hiroshima, Japan
    • Hiroshima University Hospital - Dept of Rheumatology/Immunology
  • Kagoshima, Japan
    • Eiraku Clinic - Dept of Rheumatology
  • Kanazawa, Japan
    • Kanazawa University Hospital - Dept of Rheumatology/Immunology
  • Kawagoe-shi, Japan
    • Saitama Medical Center - Dept of Rheumatology/Immunology
  • Kita-gun, Japan
    • Kagawa University Hospital - Dept of Immunology/ Rheumatology
  • Meguro-ku, Japan
    • Toho University Ohashi Medical Center - Dept of Immunology/Rheumatology
  • Sapporo, Japan
    • Hokkaido University Hospital - Dept of Internal Medicine 2(Rheumatology/Immunolog
  • Sendai, Japan
    • Tohoku University Hospital - Dept of Hematology/Immunology
  • Toon-shi, Japan
    • Ehime University Hospital - Dept of Immunology/Rheumatology
• Mauritius
  • Quatre Bornes, Mauritius
    • CAP Research Ltd
• Mexico
  • Cuernavaca, Mexico
    • Consultorio Particular del Dr. Miguel Cortes Hernandez - (dentro del Centro de Especialidades Medicas Vista
  • Guadalajara, Mexico
    • Centro de Estudios de Investigacion Basica Y Clinica SC
  • Mexicali, Mexico
    • Centro Medico del Angel
  • Mexico City, Mexico
    • CAIMED Investigacion en salud S.A de C.V.
  • México, Mexico
    • Centro de Investigacion Clínica GRAMEL S.C
  • México, Mexico
    • Consultorio de Reumatologia - Hospital Angeles Lindavista Cons. 445B
  • México, Mexico
    • Grupo Medico Camino S.C.
  • México, Mexico
    • Clinstile, S.A. de C.V.
  • México, Mexico
    • CITER, Centro de Investigacion y Tratamiento de las Enfermedades Reumaticas SA de CV
  • Torreón, Mexico
    • CIMAB S.A. de C.V. - Centro de Investigacion Medica Alberto Bazzoni
  • Yucatán, Mexico
    • Medical Care & Research SA de CV
• Moldova
  • Chisinau, Moldova
    • ICS ARENSIA Exploratory Medicine SRL - Republican Clinical Hospital "Timofei Mosneaga"
• Philippines
  • Cebu City, Philippines
    • Perpetual Succour Hospital
  • Davao City, Philippines
    • Davao Doctors Hospital - Medicine
  • Iloilo City, Philippines
    • Iloilo Doctors Hospital
  • Lipa City, Philippines
    • Mary Mediatrix Medical Center
  • Manila, Philippines
    • Chinese General Hospital & Medical Center
  • Quezon City, Philippines
    • Far Eastern University - Dr. Nicanor Reyes Medical Foundation - Department of Child Health
  • Quezon City, Philippines
    • Ospital ng Makati
• Poland
  • Bialystok, Poland
    • Nova Reuma Spolka Partnerska
  • Kościan, Poland
    • Prywatna Praktyka Lekarska prof Pawel Hrycaj
  • Krakow, Poland
    • Centrum Medyczne Plejady
  • Krakow, Poland
    • Centrum Nowoczesnych Terapii Dobry Lekarz
  • Opole, Poland
    • Twoja Przychodnia Opolskie Centrum Medyczne
  • Poznan, Poland
    • Twoja Przychodnia PCM
  • Szczecin, Poland
    • Twoja Przychodnia-Szczecinskie Centrum Medyczne
  • Warsaw, Poland
    • Clinical Best Solutions - Warszawa
• Romania
  • Bucharest, Romania
    • 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
  • Râmnicu Vâlcea, Romania
    • Sc Medaudio-Optica SRL
• Serbia
  • Belgrade, 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
  • Kragujevac, Serbia
    • University Clinical Center Kragujevac
• South Africa
  • Cape Town, South Africa
    • Arthritis Clinical Research Trial Unit - Dr CE Spargo and Dr RB Bhorat
  • Pretoria, South Africa
    • University of Pretoria Clinical Research Unit - Parent
  • Umhlanga, South Africa
    • Naidoo, A - Netcare Umhlanga Hospital
• South Korea
  • Busan, South Korea
    • Pusan National University Hospital
  • Incheon, South Korea
    • Gachon University Gil Medical Center
  • Seoul, South Korea
    • Seoul National University Hospital
  • Suwon, South Korea
    • Ajou University Hospital
• Spain
  • A Coruña, Spain
    • Complejo Hospitalario Universitario A Coruña - Servicio de Reumatologia
  • Castelló, Spain
    • Hospital General de Castellon - Servicio de Reumatologia
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre - Servicio de Reumatologia
  • Málaga, Spain
    • Hospital Regional Universitario de Malaga - Reumatology Dept
  • Santander, Spain
    • Hospital Universitario Marques de Valdecilla - Servicio de Reumatologia
  • Seville, Spain
    • Hospital Quironsalud Sagrado Corazon - Reumatologia
  • Valencia, Spain
    • Hospital Universitario Dr. Peset - Servicio de Reumatologia
  • Valladolid, Spain
    • Hospital Universitario Rio Hortega - Servicio de Medicina Interna
• Taiwan
  • Kaohsiung City, Taiwan
    • Kaohsiung Chang Gung Memorial Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taipei, Taiwan
    • Cheng Hsin General Hospital
• United States
  • California
    • Torrance, California, United States, 90509
      • The Lundquist Institute at Harbor-UCLA Medical Center
  • Florida
    • Brandon, Florida, United States, 33511
      • Bay Area Arthritis And Osteoporosis
    • Miami, Florida, United States, 33135
      • Advance Medical Research Center
    • Miami, Florida, United States, 33165
      • New Horizon Research Center, Inc
    • Miami Lakes, Florida, United States, 33014
      • Charisma Medical and Research Center
    • Orlando, Florida, United States, 32819
      • HMD Research, LLC
    • Tamarac, Florida, United States, 33321
      • D&H Tamarac Research Center, LLC
  • Georgia
    • Sugar Hill, Georgia, United States, 30518
      • RNA America Health Sciences
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Dawes Fretzin Dermatology Group, LLC
  • Michigan
    • Grand Blanc, Michigan, United States, 48439
      • AA MRC LLC Ahmed Arif Medical Research Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • North Carolina
    • Smithfield, North Carolina, United States, 27577
      • Across the Life Span
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Ohio State University - CTMO Parent
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Ramesh C Gupta, MD - Memphis, TN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	Drug: Placebo; Participants will receive placebo matched to Enpatoran up to 24 weeks.
Experimental: 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.	Drug: Enpatoran low dose; Participants will receive film-coated tablets of Enpatoran at a low dose orally, twice daily (BID) up to 24 weeks.; Other Names: M5049
Experimental: 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.	Drug: Enpatoran medium dose; Participants will receive film-coated tablets of Enpatoran at a medium dose, orally, BID up to 24 weeks.; Other Names: M5049
Experimental: 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.	Drug: Enpatoran high dose; Participants will receive film-coated tablets of Enpatoran at a high dose, orally, BID up to 24 weeks.; Other Names: M5049
Placebo Comparator: 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 .	Drug: Placebo; Participants will receive placebo matched to Enpatoran up to 24 weeks.
Experimental: 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.	Drug: Enpatoran high dose; Participants will receive film-coated tablets of Enpatoran at a high dose, orally, BID up to 24 weeks.; Other Names: M5049
Experimental: 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.	Drug: Enpatoran low dose; Participants will receive film-coated tablets of Enpatoran at a low dose orally, twice daily (BID) up to 24 weeks.; Other Names: M5049
Experimental: 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.	Drug: Enpatoran medium dose; Participants will receive film-coated tablets of Enpatoran at a medium dose, orally, BID up to 24 weeks.; Other Names: M5049

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort A and B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events (AEs) of Special Interest	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether considered related to the medicinal product or protocol-specified procedure. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious TEAEs and non-serious TEAEs. Adverse events of special interest (AESI) are serious or non-serious AEs that are of clinical interest and were closely followed.	From screening upto safety follow up period (up to approximately 33 weeks)
Cohort A and B: Number of Participants With Abnormal Laboratory Parameters	Laboratory parameters included hematology, biochemistry, Urinalysis, Renal Toxicity and Hepatotoxicity. Number of Participants with Abnormal laboratory parameters (severity of grade greater or equal to 3) were reported. Severity of grade 3 or higher TEAEs were graded using National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 toxicity grades, as follows: Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death.	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)	12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. The corrected QT interval (QTcF) was calculated using Fridericia's formula. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical importance was determined by the investigator. The number of participants with clinically important increases in QTCF findings were reported.	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	The Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) is a validated clinician-reported outcome measure used to assess disease severity in participants with cutaneous lupus erythematosus. It is based on a 5-point ordinal scale that evaluates overall lesion characteristics, where 0 indicates "clear" skin and 4 represents "severe" disease. The scale includes the following categories: 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe).	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	The Physician's Global Assessment of Disease Activity was recorded using the 100 millimeter horizontal Visual Analog Scale (VAS). The score reflects the clinician's integrated judgment based on clinical signs, symptoms, laboratory findings, and patient-reported outcomes. PGA is used to quantify disease severity and monitor treatment response over time. Physician rated participant's disease activity on a scale ranged from 0-100 millimeter (mm), where 0 indicated no disease activity and 100 represented maximum disease activity.	Baseline and at Week 16 and Week 24
Cohort B: Number of Participants With Both BICLA Response and With Clinically Meaningful Corticosteroids (CS) Reduction	BICLA (BILAG-Based Composite Lupus Assessment) defines response as improvement in all baseline BILAG A scores to B, C, or D and all B scores to C or D, with no new A scores and no more than one new B score. Responders must also show no worsening in SLEDAI-2K or Physician's Global Assessment (defined as ≥0.3-point increase). Corticosteroid (CS) reduction is defined as a decrease in daily prednisone-equivalent dose from ≥10 mg at Day 1 to ≤5 mg by Week 12, sustained through Week 24. BILAG grades reflect disease severity: A = severe disease requiring high-dose therapy; B = moderate disease requiring moderate therapy; C = mild stable disease; D = no current activity.	At week 24 (BICLA Response) and Day 1 upto Week 24 (CS Reductions)
Cohort A and B: Number of Participants 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. The number of participants with Clinically Meaningful CS Reduction were reported.	Day 1 up to Week 24
Cohort A: Number of Participants With CLA-IGA Score 0 or 1 at Week 16 and Week 24	The Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) is a validated clinician-reported outcome measure used to assess disease severity in participants with cutaneous lupus erythematosus. It is based on a 5-point ordinal scale that evaluates overall lesion characteristics, where 0 indicates "clear" skin and 4 represents "severe" disease. The scale includes the following categories: 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe). The number of participants with CLA-IGA score 0 or 1 at Week 16 and Week 24 were reported.	At Week 16 and Week 24
Cohort B: Number of Participants With Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24	SRI-4 response was defined as >= 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score, no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and no treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to Systemic Lupus Erythematosus (SLE), divided into 9 organ systems. For each organ system A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale =from 0(very well) to 100(very poor).	At Week 24
Cohort B: Number of Participants With Lupus Low Disease Activity State (LLDAS) Attainment at Week 24	Lupus Low Disease Activity State (LLDAS) Attainment at Week 24 is defined as meeting all of the following criteria at the specified time point: SLE Disease Activity Index 2000 (SLEDAI-2K) ≤4 with no activity in major organ systems, no new disease activity compared to the previous assessment, Physician's Global Assessment (PGA) ≤1, current prednisone dose ≤7.5 mg/day, and standard maintenance dosing of immunosuppressive therapies. The number of participants with LLDAS Attainment at Week 24 were reported.	At Week 24
Cohort B: Number of Participants With Remission Attainment at Week 24	Remission attainment was defined as a Clinical Hybrid Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index score of 0, Physician's Global Assessment of Systemic Lupus Erythematosus <0.5 (0-3 scale), daily prednisolone-equivalent dose ≤5 mg, and stable use of immunosuppressive therapies including biologics. Number of participants who attained remission was reported.	At Week 24
Cohort B: Percentage of Participants With 50% Reduction in Baseline Tender and Swollen Count at Week 24	The 28-joint count questionnaire assesses 14 joints on each side (28 joints overall) for both tenderness and swelling. The outcome for the assessment of each joint can be "absent", "present", "replaced" or "unable to evaluate".Tender 28-joint count will be derived as the count of joints which are tender. Swollen 28-joint count will be derived as the count of joints which are swollen. The number of tender and swollen joints will be calculated as the count of joints which are both tender and swollen. Percentage of Participants with 50% Reduction in Baseline Tender and Swollen Count at Week 24 was reported.	At Week 24
Cohort B: Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare	Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare is defined as the time from baseline to the first occurrence of moderate or severe disease activity, as measured by the BILAG Index. The BILAG Index assesses clinical signs, symptoms, and laboratory parameters related to systemic lupus erythematosus (SLE) across 9 organ systems. Each organ system is scored alphabetically: A (severe disease), B (moderate disease), C (mild stable disease), D (inactive but previously active), and E (inactive and never affected). A moderate/severe flare is defined as the presence of at least one new or worsening BILAG A score (severe disease activity) or two or more new or worsening BILAG B scores (moderate disease activity) in any organ system, compared to the previous visit. Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare was estimated via Kaplan-Meier method.	Baseline (Day 1) through Week 24
Cohort B: Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare	Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare is defined as the time from baseline to the first occurrence of a severe flare, as measured by the SLEDAI Flare Index (SFI). A severe flare is characterized by a ≥12-point increase in the SLEDAI score from the previous visit, accompanied by a ≥2.5-point increase in the physician's global assessment (on a 0-3 visual analogue scale), and a change in treatment such as initiation of corticosteroids at a dose >0.5 mg/kg/day and/or the addition of a new immunosuppressive agent. Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare was estimated via Kaplan-Meier method.	Baseline (Day 1) through Week 24
Cohort A and B: Change From Baseline in Skindex 29+3 Symptom Domain Score at Week 24	The Skindex 29+3 is a self-reported measure of skin-specific symptoms and functioning for CLE populations, and includes items from the Skindex-29, designed for use across dermatologic conditions, and 3 additional items specific for lupus. Subscale scores are generated for each of the 3 original domains of the Skindex-29 i.e., symptoms, functioning, and emotional well-being. For all subscale scores, higher scores indicate lower functioning/worse symptoms. The symptoms domain includes items measuring physical sensations such as itching, burning, stinging, and pain. Each item is rated on a 5-point Likert scale from 1 ("never") to 5 ("all the time"), and scores are transformed to a 0-100 scale, with higher scores indicating more severe symptoms.	Baseline and at week 24
Cohort A and B: Change From Baseline in the Skindex 29+3 Functioning Domain Scores at Week 24	The Skindex 29+3 is a self-reported measure of skin-specific symptoms and functioning for CLE populations, and includes items from the Skindex-29, designed for use across dermatologic conditions, and 3 additional items specific for lupus. Subscale scores are generated for each of the 3 original domains of the Skindex-29 i.e., symptoms, functioning, and emotional well-being. For all subscale scores, higher scores indicate lower functioning/worse symptoms. The functioning domain assesses the impact of skin disease on daily activities, social interactions, and work. Items are rated on a 5-point Likert scale (1 = "never" to 5 = "all the time") and transformed to a 0-100 scale, where higher scores reflect greater impairment in functioning.	Baseline and at Week 24
Cohort A and B: Change From Baseline in the Skindex 29+3 Emotion Domain Scores at Week 24	The Skindex 29+3 is a self-reported measure of skin-specific symptoms and functioning for CLE populations, and includes items from the Skindex-29, designed for use across dermatologic conditions, and 3 additional items specific for lupus. Subscale scores are generated for each of the 3 original domains of the Skindex-29 i.e., symptoms, functioning, and emotional well-being. For all subscale scores, higher scores indicate lower functioning/worse symptoms. The emotion domain of the Skindex-29+3 assesses the psychological impact of skin disease in individuals with cutaneous lupus erythematosus. It includes items that measure feelings such as embarrassment, frustration, anger, sadness, and worry related to skin symptoms. Each item is rated on a 5-point Likert scale from 1 ("never") to 5 ("all the time"), and scores are transformed to a 0-100 scale, with higher scores indicating greater emotional distress.	Baseline and at Week 24
Cohort A and B: Change From Baseline in the Skindex 29+3 Lupus-Specific Domain Scores at Week 24	The Skindex-29+3 is a self-reported measure of skin-specific symptoms and functioning for CLE populations. It includes items from the Skindex-29, designed for use across dermatologic conditions, and 3 additional items specific to lupus. Subscale scores are generated for the 3 original domains: symptoms, functioning, and emotional well-being. For all subscales, higher scores indicate worse symptoms or lower functioning. The lupus-specific domain captures symptoms and concerns unique to cutaneous lupus, including sensitivity to sunlight, flares from environmental exposure, and emotional impact of lupus-related skin changes. Each item is rated on a 5-point Likert scale from 1 ("never") to 5 ("all the time"), and scores are transformed to a 0-100 scale. Higher scores reflect greater symptom burden and disease impact.	Baseline and at Week 24
Cohort A and B: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scores at Week 24	Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) is a 13-item, self-reported questionnaire designed to assess fatigue and its impact on daily activities and functioning in individuals with chronic illness, including systemic lupus erythematosus. Each item is rated on a 5-point Likert-type scale ranging from 0 = "not at all" to 4 = "very much". Items are scored to ensure that 0 represents the worst and 4 the best possible outcome. The score ranges from 0 to 52, with higher scores indicating less fatigue and better functioning.	Baseline and at Week 24

Collaborators and Investigators

• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, EMD Serono Research & Development Institute, Inc.

Publications and helpful links

Helpful Links

• US Medical Information website, Medical Resources
• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2022
• Primary Completion (Actual): November 20, 2024
• Study Completion (Actual): November 20, 2024

Study Registration Dates

• First Submitted: December 8, 2021
• First Submitted That Met QC Criteria: December 8, 2021
• First Posted (Actual): December 17, 2021

Study Record Updates

• Last Update Posted (Actual): December 1, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Lupus; Adults; SLE; Toll-like Receptor 7; Toll-like Receptor 8; WILLOW; CLE; Discoid lupus erythematosus; Subacute cutaneous lupus erythematosus; M5049; Enpatoran
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Discoid
• Other Study ID Numbers: MS200569_0003; 2021-004648-27 (EudraCT Number); 2024-510872-18-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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
• IPD Sharing 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
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No