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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05162586
Recruitment Status : Recruiting
First Posted : December 17, 2021
Last Update Posted : March 6, 2024
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Tracking Information
First Submitted Date  ICMJE December 8, 2021
First Posted Date  ICMJE December 17, 2021
Last Update Posted Date March 6, 2024
Actual Study Start Date  ICMJE March 31, 2022
Estimated Primary Completion Date July 8, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 8, 2021)
  • Cohort A: Percent Change from Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-A) at Week 16 [ Time Frame: Baseline, Week 16 ]
  • Cohort B: British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response at Week 24 [ Time Frame: At Week 24 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2022)
  • 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 [ Time Frame: 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 [ Time Frame: Baseline, Week 16 and 24 ]
  • Cohort A and Cohort B: Change from Baseline in Physician's Global Assessment of Cutaneous Lupus Disease Activity at Week 16 and 24 [ Time Frame: 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 [ Time Frame: 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: Clinically Meaningful Corticosteroids (CS) Reduction [ Time Frame: 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 [ Time Frame: At Week 16 and 24 ]
  • Cohort B: Systemic lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24 [ Time Frame: At Week 24 ]
  • Cohort B: Lupus Low Disease Activity State (LLDAS) Attainment at Week 24 [ Time Frame: At Week 24 ]
  • Cohort B: Remission Attainment at Week 24 [ Time Frame: At Week 24 ]
  • Cohort B: Change From Baseline in Tender Joint Count and Swollen Joint Count at Week 24 [ Time Frame: Baseline, Week 24 ]
  • Cohort B: Change from Baseline in Physician's Global Assessment at Week 24 [ Time Frame: Baseline, Week 24 ]
  • Cohort B: Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare [ Time Frame: Day 1 through Week 24 ]
  • Cohort B: Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare [ Time Frame: Day 1 through Week 24 ]
  • Cohort A and B: Change from Baseline in Skindex 29+3 Symptom Domain Score at Week 24 [ Time Frame: Baseline, Week 24 ]
  • Cohort A and B: Change from Baseline in the Skindex 29+3 Functioning and Emotion Domain Scores at Week 24 [ Time Frame: Baseline, Week 24 ]
  • Change from Baseline in the Skindex 29+3 Lupus-Specific Domain Score at Week 24 [ Time Frame: Baseline, Week 24 ]
  • Cohort A and B: Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scores at Week 24 [ Time Frame: Baseline, Week 24 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 8, 2021)
  • 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 [ Time Frame: 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 [ Time Frame: Baseline, Week 16 and 24 ]
  • Cohort A and Cohort B: Change from Baseline in Physician's Global Assessment of Cutaneous Lupus Disease Activity at Week 16 and 24 [ Time Frame: 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 [ Time Frame: 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: Clinically Meaningful Corticosteroids (CS) Reduction [ Time Frame: 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 [ Time Frame: At Week 16 and 24 ]
  • Cohort B: Systemic lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24 [ Time Frame: At Week 24 ]
  • Cohort B: Lupus Low Disease Activity State (LLDAS) Attainment at Week 24 [ Time Frame: At Week 24 ]
  • Cohort B: Remission Attainment at Week 24 [ Time Frame: At Week 24 ]
  • Cohort B: Change From Baseline in Tender Joint Count and Swollen Joint Count at Week 24 [ Time Frame: Baseline, Week 24 ]
  • Cohort B: Change from Baseline in Physician's Global Assessment at Week 24 [ Time Frame: Baseline, Week 24 ]
  • Cohort B: Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare [ Time Frame: Day 1 through Week 24 ]
  • Cohort B: Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare [ Time Frame: Day 1 through Week 24 ]
  • Cohort A and B: Change from Baseline in Skindex 29+3 Symptom Domain Score at Week 24 [ Time Frame: Baseline, Week 24 ]
  • Cohort A and B: Change from Baseline in the Skindex 29+3 Functioning and Emotion Domain Scores at Week 24 [ Time Frame: Baseline, Week 24 ]
  • Cohort A and B: Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scores at Week 24 [ Time Frame: Baseline, Week 24 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The WILLOW Study With M5049 in SLE and CLE (SCLE and/or DLE) (WILLOW)
Official Title  ICMJE 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)
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Systemic Lupus Erythematosus
Intervention  ICMJE
  • 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 Name: M5049
  • Drug: Enpatoran medium dose
    Participants will receive film-coated tablets of Enpatoran at a medium dose, orally, BID up to 24 weeks.
    Other Name: M5049
  • Drug: Enpatoran high dose
    Participants will receive film-coated tablets of Enpatoran at a high dose, orally, BID up to 24 weeks.
    Other Name: M5049
  • Drug: Placebo
    Participants will receive placebo matched to Enpatoran up to 24 weeks.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Placebo
  • 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.
    Intervention: Drug: Enpatoran low dose
  • 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.
    Intervention: Drug: Enpatoran medium dose
  • 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.
    Intervention: Drug: Enpatoran high dose
  • 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 .
    Intervention: Drug: Placebo
  • 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.
    Intervention: Drug: Enpatoran high dose
  • 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.
    Intervention: Drug: Enpatoran low dose
  • 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.
    Intervention: Drug: Enpatoran medium dose
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 14, 2023)
532
Original Estimated Enrollment  ICMJE
 (submitted: December 8, 2021)
440
Estimated Study Completion Date  ICMJE August 16, 2024
Estimated Primary Completion Date July 8, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US Medical Information 888-275-7376 eMediUSA@emdserono.com
Contact: Communication Center +49 6151 72 5200 service@emdgroup.com
Listed Location Countries  ICMJE 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,   United States
Removed Location Countries Germany
 
Administrative Information
NCT Number  ICMJE NCT05162586
Other Study ID Numbers  ICMJE MS200569_0003
2021-004648-27 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: Analytic Code
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
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.
URL: https://bit.ly/IPD21
Current Responsible Party EMD Serono ( EMD Serono Research & Development Institute, Inc. )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE EMD Serono Research & Development Institute, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Merck KGaA, Darmstadt, Germany
Investigators  ICMJE
Study Director: Medical Responsible EMD Serono Research & Development Institute, Inc.
PRS Account EMD Serono
Verification Date February 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP