Study of M5049 in CLE and SLE Participants

Systemic Lupus Erythematosus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04647708
• Other study ID #: MS200569_0004
• Secondary ID: 2020-003118-11
• Status: Completed
• Phase: Phase 1
• Start date: December 16, 2020
• Est. completion date: December 19, 2023

Study information

• Verified date: February 2024
• Source: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: December 19, 2023
• Est. primary completion date: December 19, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Cutaneous Lupus Erythematosus
• Lupus Erythematosus, Cutaneous
• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• M5049
Participants will receive low oral dose of M5049, twice daily in Part A.
• M5049
Participants will receive ascending oral dose of M5049, twice daily in Part A.
• M5049
Participants will receive high oral dose of M5049, twice daily in Part B.
• Placebo
Participants will receive placebo matched to M5049.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

Bulgaria,  Germany,  Moldova, Republic of,  North Macedonia,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Part A: Cohort 1 and 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Based on Severity		Up to Day 102
Primary	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
Primary	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
Primary	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
Primary	Part A: Cohort 1 and 2: Number of Participants with Confirmed Signs and Symptoms of Prodromal Seizure		Up to Day 102
Primary	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
Primary	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	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
Secondary	Part A and Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M5049		Day 1 and Day 29
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part A and Part B: Elimination Rate Constant (Lambda z) of M5049		Day 1 and Day 29
Secondary	Part A and Part B: Apparent Terminal Half-life (t1/2) of M5049		Day 1 and Day 29
Secondary	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
Secondary	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
Secondary	Part A and Part B: Total Body Clearance (CL/f) of M5049		Day 1
Secondary	Part A and Part B: Apparent Volume of Distribution (Vz/f) of M5049		Day 1
Secondary	Part A and Part B: Area Under Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of M5049		Day 1
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Trial Awareness and Transparency website