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

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ClinicalTrials.gov Identifier: NCT05162586
Recruitment Status : Recruiting
First Posted : December 17, 2021
Last Update Posted : October 18, 2022
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Brief Summary:
The purpose of this Proof of Concept (PoC) and Dose-finding (DF) basket study is to evaluate the efficacy and safety of orally administered M5049 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 M5049 is not available through an expanded access program.

Condition or disease Intervention/treatment Phase
Systemic Lupus Erythematosus Drug: M5049 low dose Drug: M5049 medium dose Drug: M5049 high dose Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 440 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : March 31, 2022
Estimated Primary Completion Date : July 8, 2024
Estimated Study Completion Date : August 16, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus

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 M5049.
Drug: Placebo
Participants will receive placebo matched to M5049 up to 24 weeks.

Experimental: Cohort A: M5049 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 M5049.
Drug: M5049 low dose
Participants will receive film-coated tablets of M5049 at a low dose orally, twice daily (BID) up to 24 weeks.
Other Name: Enpatoran

Experimental: Cohort A: M5049 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 M5049.
Drug: M5049 medium dose
Participants will receive film-coated tablets of M5049 at a medium dose, orally, BID up to 24 weeks.
Other Name: Enpatoran

Experimental: Cohort A: M5049 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 M5049.
Drug: M5049 high dose
Participants will receive film-coated tablets of M5049 at a high dose, orally, BID up to 24 weeks.
Other Name: Enpatoran

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 M5049.
Drug: Placebo
Participants will receive placebo matched to M5049 up to 24 weeks.

Experimental: Cohort B (Part 1 + Part 2): M5049 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 M5049.
Drug: M5049 high dose
Participants will receive film-coated tablets of M5049 at a high dose, orally, BID up to 24 weeks.
Other Name: Enpatoran

Experimental: Cohort B (Part 2): M5049 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: M5049 low dose
Participants will receive film-coated tablets of M5049 at a low dose orally, twice daily (BID) up to 24 weeks.
Other Name: Enpatoran

Experimental: Cohort B (Part 2): M5049 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 M5049.
Drug: M5049 medium dose
Participants will receive film-coated tablets of M5049 at a medium dose, orally, BID up to 24 weeks.
Other Name: Enpatoran




Primary Outcome Measures :
  1. 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 ]
  2. Cohort B: British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response at Week 24 [ Time Frame: At Week 24 ]

Secondary Outcome Measures :
  1. 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) ]
  2. 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 ]
  3. 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 ]
  4. 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.

  5. 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.

  6. 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 ]
  7. Cohort B: Systemic lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24 [ Time Frame: At Week 24 ]
  8. Cohort B: Lupus Low Disease Activity State (LLDAS) Attainment at Week 24 [ Time Frame: At Week 24 ]
  9. Cohort B: Remission Attainment at Week 24 [ Time Frame: At Week 24 ]
  10. Cohort B: Change From Baseline in Tender Joint Count and Swollen Joint Count at Week 24 [ Time Frame: Baseline, Week 24 ]
  11. Cohort B: Change from Baseline in Physician's Global Assessment at Week 24 [ Time Frame: Baseline, Week 24 ]
  12. Cohort B: Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare [ Time Frame: Day 1 through Week 24 ]
  13. Cohort B: Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare [ Time Frame: Day 1 through Week 24 ]
  14. Cohort A and B: Change from Baseline in Skindex 29+3 Symptom Domain Score at Week 24 [ Time Frame: Baseline, Week 24 ]
  15. 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 ]
  16. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05162586


Contacts
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Contact: US Medical Information 888-275-7376 eMediUSA@emdserono.com
Contact: Communication Center +49 6151 72 5200 service@emdgroup.com

Locations
Show Show 86 study locations
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Medical Responsible EMD Serono Research & Development Institute, Inc.
Additional Information:
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Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT05162586    
Other Study ID Numbers: MS200569_0003
2021-004648-27 ( EudraCT Number )
First Posted: December 17, 2021    Key Record Dates
Last Update Posted: October 18, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
Toll-like Receptor 7
Toll-like Receptor 8
WILLOW
Adults
SLE
CLE
Lupus
Discoid lupus erythematosus
Subacute cutaneous lupus erythematosus
M5049
Enpatoran
Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases