Study of M5049 in CLE and SLE Participants

Study Overview
=================
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).

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

Conditions
-----------------
Systemic Lupus Erythematosus, Cutaneous Lupus Erythematosus

Intervention / Treatment
-----------------
* Drug: M5049
* Drug: M5049
* Drug: M5049
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lupus Erythematosus, Systemic, Lupus Erythematosus, Cutaneous, Autoimmune Diseases