Study of M5049 in CLE and SLE Participants
Phase 1
Completed
- Conditions
- Systemic Lupus ErythematosusCutaneous Lupus Erythematosus
- Interventions
- Drug: Placebo
- Registration Number
- NCT04647708
- Lead Sponsor
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 25
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A (Cohort 4): M5049 Dose D M5049 - Part B: Placebo Placebo - Part A (Cohort 1): M5049 Dose A M5049 - Part A (Cohort 2): M5049 Dose B M5049 - Part B (Cohort 5): M5049 Dose E M5049 - Part A: Placebo Placebo - Part A (Cohort 3): M5049 Dose C M5049 -
- Primary Outcome Measures
Name Time Method 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 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 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 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), 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 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
Name Time Method Part A and Part B: Apparent Terminal Half-life (t1/2) of M5049 Day 1 and Day 29 Part A and Part B: Total Body Clearance (CL/f) of M5049 Day 1 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: 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: 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: Apparent Volume of Distribution (Vz/f) of M5049 Day 1 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: 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: Elimination Rate Constant (Lambda z) of M5049 Day 1 and Day 29 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: 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: 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 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 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: 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
Trial Locations
- Locations (12)
SocraTec R&D GmbH
🇩🇪Erfurt, Germany
Fraunhofer ITMP (Fraunhofer Institute for Translational Medicine and Pharmacology)
🇩🇪Frankfurt, Germany
Medical Center-1-Sevlievo EOOD
🇧🇬Sevlievo, Bulgaria
Hospital Universitario Rio Hortega - Servicio de Medicina Interna
🇪🇸Valladolid, Spain
Hospital Universitario Nuestra Señora de Valme
🇪🇸Sevilla, Spain
PHI University Clinic of Rheumatology Skopje
🇲🇰Skopje, North Macedonia
Medical center Medconsult Pleven OOD
🇧🇬Pleven, Bulgaria
Medical Center of Limited Liability Company "Harmoniya krasy", Department of clinical trials
🇺🇦Kyiv, Ukraine
Military Medical Academy - MHAT - Sofia
🇧🇬Sofia, Bulgaria
ARENSIA Exploratory Medicine Phase I Unit, Clinical Republican Hospital
🇲🇩Chisinau, Moldova, Republic of
UMHAT "Sv. Ivan Rilski", EAD
🇧🇬Sofia, Bulgaria
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain