Study of M5049 in CLE and SLE Participants

NCT04647708 | Completed Phase 1

• 2 other identifiers: MS200569_00042020-003118-11
• Study Type: interventional
• Target: 25
• Locations: 6 countries
• Sites: 12

Brief Summary

This study is to evaluate the safety, tolerability and pharmacokinetics (PK) of orally administered M5049 in participants with systemic lupus erythematosus (SLE) or cutaneous lupus erythematosus (CLE).

Conditions

Systemic Lupus Erythematosus; Cutaneous Lupus Erythematosus

Keywords

Lupus Erythematosus, Systemic; Lupus Erythematosus, Cutaneous; Autoimmune Diseases

Outcome Measures

Primary Outcomes (9)

• Part A: Cohort 1 and 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Event of Special Interest (AESI), TEAEs Leading to Permanent Treatment Discontinuation and Treatment-Related TEAEs

  Up to Day 102

• Part A: Cohort 3 and 4; Part B: Cohort 5: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Event of Special Interest (AESI), TEAEs Leading to Permanent Treatment Discontinuation and Treatment-Related TEAEs

  Up to Day 186

• Part A: Cohort 1 and 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Based on Severity

  Up to Day 102

• Part A: Cohort 3 and 4; Part B: Cohort 5: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Based on Severity

  Up to Day 186

• Part A: Cohort 1 and 2: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters, Vital Signs, Electroencephalogram (EEG) and Electrocardiogram (ECG) Findings

  Up to Day 102

• Part A: Cohort 3 and 4; Part B: Cohort 5: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters, Vital Signs, Electroencephalogram (EEG) and Electrocardiogram (ECG) Findings

  Up to Day 186

• Part A: Cohort 1 and 2: Number of Participants with Confirmed Signs and Symptoms of Prodromal Seizure

  Up to Day 102

• Part A: Cohort 3 and 4; Part B: Cohort 5: Number of Participants with Confirmed Signs and Symptoms of Prodromal Seizure

  Up to Day 186

• Part A: Cohort 1 and 2: Number of Participants with Suicidal Behavior and Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)

  Up to Day 102

Secondary Outcomes (18)

• Part A and Part B: Maximum Observed Plasma Concentration (Cmax) of M5049

  Pre-dose up to Day 85 for Cohort 1 and 2 of Part A, up to Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B

• Part A and Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M5049

  Day 1 and Day 29

• Part A and Part B: Time to Reach Maximum Plasma Concentration (tmax) of M5049

  Pre-dose up to Day 85 for Cohort 1 and 2 of Part A, up to Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B

• Part A and Part B: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M5049

  Pre-dose up to Day 85 for Cohort 1 and 2 of Part A, up to Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B

• Part A and Part B: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of M5049

  Day 1 and Day 29

Study Arms (7)

Part A (Cohort 1): M5049 Dose A

EXPERIMENTAL

Drug: M5049

Part A (Cohort 2): M5049 Dose B

EXPERIMENTAL

Drug: M5049

Part A (Cohort 3): M5049 Dose C

EXPERIMENTAL

Drug: M5049

Part A (Cohort 4): M5049 Dose D

EXPERIMENTAL

Drug: M5049

Part A: Placebo

PLACEBO COMPARATOR

Drug: Placebo

Part B (Cohort 5): M5049 Dose E

EXPERIMENTAL

Drug: M5049

Part B: Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

M5049 DRUG

Participants will receive low oral dose of M5049, twice daily in Part A.

Part A (Cohort 1): M5049 Dose A

Placebo DRUG

Participants will receive placebo matched to M5049.

Part A: Placebo; Part B: Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Active systemic lupus erythematosus (SLE) with a Cutaneous lupus erythematosus disease area and activity index (CLASI-A) greater than or equal to \[\>= \] 6 and/or at least one active SLE clinical manifestation according to Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
• Active cutaneous lupus erythematosus (CLE) (subacute cutaneous lupus erythematosus and/or discoid lupus erythematosus) with a CLASI-A \>= 6

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany: lead

Study Sites (12)

Medical center Medconsult Pleven OOD

Pleven, Bulgaria

Location

Medical Center-1-Sevlievo EOOD

Sevlievo, Bulgaria

Location

Military Medical Academy - MHAT - Sofia

Sofia, Bulgaria

Location

UMHAT "Sv. Ivan Rilski", EAD

Sofia, Bulgaria

Location

SocraTec R&D GmbH

Erfurt, Germany

Location

Fraunhofer ITMP (Fraunhofer Institute for Translational Medicine and Pharmacology)

Frankfurt, Germany

Location

ARENSIA Exploratory Medicine Phase I Unit, Clinical Republican Hospital

Chisinau, Moldova

Location

PHI University Clinic of Rheumatology Skopje

Skopje, North Macedonia

Location

Hospital Universitario Nuestra Señora de Valme

Seville, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

Hospital Universitario Rio Hortega - Servicio de Medicina Interna

Valladolid, Spain

Location

Medical Center of Limited Liability Company "Harmoniya krasy", Department of clinical trials

Kyiv, Ukraine

Location

Related Publications (2)

• Witte T, Fernandez-Ruiz R, Abramova N, Weinelt D, Moreau F, Klopp-Schulze L, Shaw J, Denis D, Wenzel J. Enpatoran, a first-in-class, selective, orally administered toll-like receptor 7/8 inhibitor, in systemic and cutaneous lupus erythematosus: results from a randomised, placebo-controlled phase Ib study. Lupus Sci Med. 2025 Oct 23;12(2):e001705. doi: 10.1136/lupus-2025-001705.

  PMID: 41136221 DERIVED

• Klopp-Schulze L, Shaw JV, Dong JQ, Khandelwal A, Vazquez-Mateo C, Goteti K. Applying Modeling and Simulations for Rational Dose Selection of Novel Toll-Like Receptor 7/8 Inhibitor Enpatoran for Indications of High Medical Need. Clin Pharmacol Ther. 2022 Aug;112(2):297-306. doi: 10.1002/cpt.2606. Epub 2022 May 21.

  PMID: 35390178 DERIVED

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Lupus Erythematosus, Cutaneous; Autoimmune Diseases

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases; Skin Diseases

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2020
• First Posted: December 1, 2020
• Study Start: December 16, 2020
• Primary Completion: December 19, 2023
• Study Completion: December 19, 2023
• Last Updated: February 21, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); BU (4); UA (1); NO (1); ES (3); MO (1)