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Study of M5049 in CLE and SLE Participants

Primary Purpose

Systemic Lupus Erythematosus, Cutaneous Lupus Erythematosus

Status

Active

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

M5049

Placebo

About this trial

This is an interventional treatment trial for Systemic Lupus Erythematosus focused on measuring Lupus Erythematosus, Systemic, Lupus Erythematosus, Cutaneous, Autoimmune Diseases

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Part A (Cohort 1): M5049 Dose A

Part A (Cohort 2): M5049 Dose B

Part A (Cohort 3): M5049 Dose C

Part A (Cohort 4): M5049 Dose D

Part A: Placebo

Part B (Cohort 5): M5049 Dose E

Part B: Placebo

Arm Description

Outcomes

Primary Outcome Measures

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

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

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

Part A: Cohort 3 and 4; Part B: Cohort 5: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Based on Severity

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

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

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

Part A: Cohort 3 and 4; Part B: Cohort 5: Number of Participants with Confirmed Signs and Symptoms of Prodromal Seizure

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)

Secondary Outcome Measures

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

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

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

Part A and Part B: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M5049

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

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

Part A and Part B: Elimination Rate Constant (Lambda z) of M5049

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

Part A and Part B: Area Under the Plasma Concentration-Time Curve From Time Zero to 12 Hours Post-Dose (AUC0-12h) of M5049

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

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

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

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

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

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

Part A and Part B: Change from Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)

Part A and Part B: Change from Baseline in 28-Joint Count

Part A and Part B: Change from Baseline in Physician Global Assessment (PGA) Score

Full Information

NCT ID

NCT04647708

First Posted

November 23, 2020

Last Updated

October 20, 2023

Sponsor

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

1. Study Identification

Unique Protocol Identification Number

NCT04647708

Brief Title

Study of M5049 in CLE and SLE Participants

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

December 16, 2020 (Actual)

Primary Completion Date

December 22, 2023 (Anticipated)

Study Completion Date

December 22, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Systemic Lupus Erythematosus, Cutaneous Lupus Erythematosus

Keywords

Lupus Erythematosus, Systemic, Lupus Erythematosus, Cutaneous, Autoimmune Diseases

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A (Cohort 1): M5049 Dose A

Arm Type

Experimental

Arm Title

Part A (Cohort 2): M5049 Dose B

Arm Type

Experimental

Arm Title

Part A (Cohort 3): M5049 Dose C

Arm Type

Experimental

Arm Title

Part A (Cohort 4): M5049 Dose D

Arm Type

Experimental

Arm Title

Part A: Placebo

Arm Type

Placebo Comparator

Arm Title

Part B (Cohort 5): M5049 Dose E

Arm Type

Experimental

Arm Title

Part B: Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

M5049

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

M5049

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

M5049

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Participants will receive placebo matched to M5049.

Primary Outcome Measure Information:

Title

Time Frame

Up to Day 102

Title

Time Frame

Up to Day 186

Title

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

Time Frame

Up to Day 102

Title

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

Title

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

Title

Time Frame

Up to Day 186

Title

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

Time Frame

Up to Day 102

Title

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

Title

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)

Time Frame

Up to Day 102

Secondary Outcome Measure Information:

Title

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

Title

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

Time Frame

Day 1 and Day 29

Title

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

Title

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

Title

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

Title

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

Title

Part A and Part B: Elimination Rate Constant (Lambda z) of M5049

Time Frame

Day 1 and Day 29

Title

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

Time Frame

Day 1 and Day 29

Title

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

Title

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

Title

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

Time Frame

Day 1

Title

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

Time Frame

Day 1

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Responsible

Organizational Affiliation

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

Official's Role

Study Director

Facility Information:

Facility Name

Medical center Medconsult Pleven OOD

City

Pleven

Country

Bulgaria

Facility Name

Medical Center-1-Sevlievo EOOD

City

Sevlievo

Country

Bulgaria

Facility Name

Military Medical Academy - MHAT - Sofia

City

Sofia

Country

Bulgaria

Facility Name

UMHAT "Sv. Ivan Rilski", EAD

City

Sofia

Country

Bulgaria

Facility Name

SocraTec R&D GmbH

City

Erfurt

Country

Germany

Facility Name

Fraunhofer ITMP (Fraunhofer Institute for Translational Medicine and Pharmacology)

City

Frankfurt

Country

Germany

Facility Name

ARENSIA Exploratory Medicine Phase I Unit, Clinical Republican Hospital

City

Chisinau

Country

Moldova, Republic of

Facility Name

PHI University Clinic of Rheumatology Skopje

City

Skopje

Country

North Macedonia

Facility Name

Hospital Universitario Nuestra Señora de Valme

City

Sevilla

Country

Spain

Facility Name

Hospital Universitario Virgen del Rocio

City

Sevilla

Country

Spain

Facility Name

Hospital Universitario Rio Hortega - Servicio de Medicina Interna

City

Valladolid

Country

Spain

Facility Name

Medical Center of Limited Liability Company "Harmoniya krasy", Department of clinical trials

City

Kyiv

Country

Ukraine

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://bit.ly/IPD21

Citations:

PubMed Identifier

35390178

Citation

Klopp-Schulze L, Shaw JV, Dong JQ, Khandelwal A, Vazquez-Mateo C, Goteti K. Applying Modeling and Simulations for Rational Dose Selection of Novel Toll-Like Receptor 7/8 Inhibitor Enpatoran for Indications of High Medical Need. Clin Pharmacol Ther. 2022 Aug;112(2):297-306. doi: 10.1002/cpt.2606. Epub 2022 May 21.

Results Reference

derived

Links:

URL

https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS200569_0004

Description

Trial Awareness and Transparency website

Learn more about this trial

Study of M5049 in CLE and SLE Participants

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