Study of M5049 in CLE and SLE Participants

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany25 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Systemic Lupus Erythematosus Cutaneous Lupus Erythematosus

Interventions

M5049DRUG

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

M5049DRUG

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

M5049DRUG

Participants will receive high oral dose of M5049, twice daily in Part B.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (12)

Medical center Medconsult Pleven OOD

Pleven, Bulgaria

Medical Center-1-Sevlievo EOOD

Sevlievo, Bulgaria

Military Medical Academy - MHAT - Sofia

Sofia, Bulgaria

Outcomes

Primary Outcomes

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

Time frame: 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

Time frame: Up to Day 186

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Up to Day 186

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

Time frame: 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

Time frame: Up to Day 186

Data from ClinicalTrials.gov

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Secondary Outcomes

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

Time frame: 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

Time frame: Day 1 and Day 29

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

Time frame: 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

Time frame: 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

Time frame: Day 1 and Day 29

Part A and Part B: Accumulation Ratio for Maximum Observed Plasma Concentration (Racc Cmax) of M5049

Time frame: 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

Time frame: Day 1 and Day 29

Part A and Part B: Apparent Terminal Half-life (t1/2) of M5049

Time frame: 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

Time frame: 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

Time frame: Day 29

Part A and Part B: Total Body Clearance (CL/f) of M5049

Time frame: Day 1

Part A and Part B: Apparent Volume of Distribution (Vz/f) of M5049

Time frame: Day 1

Part A and Part B: Area Under Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of M5049

Time frame: 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

Time frame: Day 1

Part A and Part B: Change from Baseline in Cutaneous Lupus Erythematosus Disease Area and Activity Index (CLASI-A)

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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