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

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 2

Conditions: Systemic Lupus Erythematosus

Treatments: Drug: Placebo; Drug: Enpatoran low dose; Drug: Enpatoran high dose; Drug: Enpatoran medium dose

Study type: Interventional

Funder types: Industry

Identifiers

NCT05162586

2021-004648-27 (EudraCT Number)

MS200569_0003

Details and patient eligibility

About

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.

Enrollment: 456 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

456 participants in 8 patient groups, including a placebo group

Cohort A: Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Cohort A: Enpatoran low dose

Experimental group

Description:

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.

Treatment:

Drug: Enpatoran low dose

Cohort A: Enpatoran medium dose

Experimental group

Description:

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.

Treatment:

Drug: Enpatoran medium dose

Cohort A: Enpatoran high dose

Experimental group

Description:

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.

Treatment:

Drug: Enpatoran high dose

Cohort B (Part 1 + Part 2): Placebo

Placebo Comparator group

Description:

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 .

Treatment:

Drug: Placebo

Cohort B (Part 1 + Part 2): Enpatoran high dose

Experimental group

Description:

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.

Treatment:

Drug: Enpatoran high dose

Cohort B (Part 2): Enpatoran low dose

Experimental group

Description:

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.

Treatment:

Drug: Enpatoran low dose

Cohort B (Part 2): Enpatoran medium dose

Experimental group

Description:

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.

Treatment:

Drug: Enpatoran medium dose