Cutaneous Lupus Erythematosus, Systemic Lupus Erythematosus
Conditions
Keywords
Lupus Erythematosus, Systemic, Lupus Erythematosus, Cutaneous, Autoimmune Diseases
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).
Interventions
DRUGM5049
Participants will receive low oral dose of M5049, twice daily in Part A.
DRUGPlacebo
Participants will receive placebo matched to M5049.
Sponsors
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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: 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: 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 |
| 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: 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 |
Countries
Bulgaria, Germany, Moldova, North Macedonia, Spain, Ukraine
Outcome results
None listed