Study of M5049 in CLE and SLE Participants

A Phase Ib, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Safety and Pharmacokinetics of Multiple Ascending Doses of M5049 Administered Orally in SLE and CLE Participants Treated With Standard of Care

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).

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus; Cutaneous Lupus Erythematosus
• Intervention / Treatment: Drug: M5049; Drug: M5049; Drug: M5049; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria
    • Medical Center Medconsult Pleven Ood
  • Sevlievo, Bulgaria
    • Medical Center-1-Sevlievo EOOD
  • Sofia, Bulgaria
    • Military Medical Academy - MHAT - Sofia
  • Sofia, Bulgaria
    • UMHAT "Sv. Ivan Rilski", EAD
• Germany
  • Erfurt, Germany
    • SocraTec R&D GmbH
  • Frankfurt, Germany
    • Fraunhofer ITMP (Fraunhofer Institute for Translational Medicine and Pharmacology)
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • ARENSIA Exploratory Medicine Phase I Unit, Clinical Republican Hospital
• North Macedonia
  • Skopje, North Macedonia
    • PHI University Clinic of Rheumatology Skopje
• Spain
  • Sevilla, Spain
    • Hospital Universitario Virgen del Rocio
  • Sevilla, Spain
    • Hospital Universitario Nuestra Señora de Valme
  • Valladolid, Spain
    • Hospital Universitario Rio Hortega - Servicio de Medicina Interna
• Ukraine
  • Kyiv, Ukraine
    • Medical Center of Limited Liability Company "Harmoniya krasy", Department of clinical trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
• 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: Sequential Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A (Cohort 1): M5049 Dose A	Drug: M5049; Participants will receive low oral dose of M5049, twice daily in Part A.; Drug: M5049; Participants will receive ascending oral dose of M5049, twice daily in Part A.; Drug: M5049; Participants will receive high oral dose of M5049, twice daily in Part B.
Experimental: Part A (Cohort 2): M5049 Dose B	Drug: M5049; Participants will receive low oral dose of M5049, twice daily in Part A.; Drug: M5049; Participants will receive ascending oral dose of M5049, twice daily in Part A.; Drug: M5049; Participants will receive high oral dose of M5049, twice daily in Part B.
Experimental: Part A (Cohort 3): M5049 Dose C	Drug: M5049; Participants will receive low oral dose of M5049, twice daily in Part A.; Drug: M5049; Participants will receive ascending oral dose of M5049, twice daily in Part A.; Drug: M5049; Participants will receive high oral dose of M5049, twice daily in Part B.
Experimental: Part A (Cohort 4): M5049 Dose D	Drug: M5049; Participants will receive low oral dose of M5049, twice daily in Part A.; Drug: M5049; Participants will receive ascending oral dose of M5049, twice daily in Part A.; Drug: M5049; Participants will receive high oral dose of M5049, twice daily in Part B.
Placebo Comparator: Part A: Placebo	Drug: Placebo; Participants will receive placebo matched to M5049.
Experimental: Part B (Cohort 5): M5049 Dose E	Drug: M5049; Participants will receive low oral dose of M5049, twice daily in Part A.; Drug: M5049; Participants will receive ascending oral dose of M5049, twice daily in Part A.; Drug: M5049; Participants will receive high oral dose of M5049, twice daily in Part B.
Placebo Comparator: Part B: Placebo	Drug: Placebo; Participants will receive placebo matched to M5049.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Part A and Part B: Accumulation Ratio for Maximum Observed Plasma Concentration (Racc 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: Elimination Rate Constant (Lambda z) of M5049	Day 1 and Day 29
Part A and Part B: Apparent Terminal Half-life (t1/2) of M5049	Day 1 and Day 29
Part A and Part B: Area Under the Plasma Concentration-Time Curve From Time Zero to 12 Hours Post-Dose (AUC0-12h) of M5049	Day 29
Part A and Part B: Dose Normalized Area Under Plasma Concentration-Time Curve from Time Zero to 12 Hours Post-Dose (AUC0-12h/Dose) of M5049	Day 29
Part A and Part B: Total Body Clearance (CL/f) of M5049	Day 1
Part A and Part B: Apparent Volume of Distribution (Vz/f) of M5049	Day 1
Part A and Part B: Area Under Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of M5049	Day 1
Part A and Part B: Dose Normalized Area Under Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of M5049	Day 1
Part A and Part B: Change from Baseline in Cutaneous Lupus Erythematosus Disease Area and Activity Index (CLASI-A)	Baseline (Day 1) through Day 85 for Cohort 1 and 2 of Part A, Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B
Part A and Part B: Change from Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)	Baseline (Day 1) through Day 85 for Cohort 1 and 2 of Part A, Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B
Part A and Part B: Change from Baseline in 28-Joint Count	Baseline (Day 1) through Day 85 for Cohort 1 and 2 of Part A, Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B
Part A and Part B: Change from Baseline in Physician Global Assessment (PGA) Score	Baseline (Day 1) through Day 85 for Cohort 1 and 2 of Part A, Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B

Collaborators and Investigators

• Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

General Publications

• 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.

Helpful Links

• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2020
• Primary Completion (Actual): December 19, 2023
• Study Completion (Actual): December 19, 2023

Study Registration Dates

• First Submitted: November 23, 2020
• First Submitted That Met QC Criteria: November 23, 2020
• First Posted (Actual): December 1, 2020

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Autoimmune Diseases; Lupus Erythematosus, Systemic; Lupus Erythematosus, Cutaneous
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Erythematosus, Cutaneous
• Other Study ID Numbers: MS200569_0004; 2020-003118-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• 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 the 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 https://bit.ly/IPD21

Drug and device information, study documents

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