Study of M5049 in DM and PM Participants (NEPTUNIA)

NCT05650567 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: MS200569_00412022-501351-82-00
• Study Type: interventional
• Target: 40
• Locations: 7 countries
• Sites: 31

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of orally administered M5049 in idiopathic inflammatory myopathies, specifically dermatomyositis (DM) and polymyositis (PM) participants for 24 weeks.

Conditions

Dermatomyositis; Polymyositis

Keywords

Toll-like Receptor 7; Toll-like Receptor 8; Anti-synthetase syndrome; Idiopathic immune myopathies; Myositis; M5049

Outcome Measures

Primary Outcomes (3)

• DBPC Period: American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Total Improvement Score (TIS) at Week 24

  at Week 24

• DBPC Period: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)

  up to Week 26

• DBPC Period: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters, Vital Signs and 12-Lead Electrocardiogram (ECG) Measurements

  up to Week 26

Secondary Outcomes (13)

• DBPC Period: Number of Participants with American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Total Improvement Score (TIS) Greater Than or Equal to (>=) 20, >= 40 and >= 60

  Week 16 and Week 24

• DBPC Period: Total Improvement Score (TIS)

  Week 4 up to Week 20

• DBPC Period: Mean Score for Core Set Measures (CSM) from Week 4 up to Week 24.

  Week 4 up to Week 24

• DBPC Period: Percent Change from Baseline in Most Abnormal Muscle-associated Enzyme at Weeks 4, 8, 12, 16, 20 and 24

  Baseline, Weeks 4, 8, 12, 16, 20 and 24

• DBPC Period: Absolute Change from Baseline in the Core Set Measures (CSM) at Weeks 4, 8, 12, 16, 20 and 24'

  Baseline, Weeks 4, 8, 12, 16, 20 and 24

Study Arms (3)

Double-blind Placebo Controlled (DBPC) Period: M5049 high dose

EXPERIMENTAL

Drug: M5049 high dose

DBPC Period: Placebo

PLACEBO COMPARATOR

Drug: Placebo

Open Label Extension (OLE) Period: M5049 high dose

EXPERIMENTAL

Drug: M5049 high dose

Interventions

M5049 high dose DRUG

Participants will receive film-coated tablets of M5049 at a high dose orally, twice daily up to 24 weeks.

Also known as: Enpatoran

Double-blind Placebo Controlled (DBPC) Period: M5049 high dose; Open Label Extension (OLE) Period: M5049 high dose

Placebo DRUG

Participants will receive placebo matched to M5049 orally, twice daily up to 24 weeks.

DBPC Period: Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of probable or definite DM or PM as per 2017 ACR/EULAR classification criteria, with positive autoantibody status. Anti-synthetase syndrome (ASyS) participants that meet classification criteria are allowed
• Active disease on standard of care (SoC), must meet 1 of the criteria within 6 months prior to Screening: Pathological evidence of active myositis in muscle biopsy; Evidence of active myositis by Electromyography (EMG); Magnetic resonance imaging (MRI) with evidence of active myositis; or any muscle enzyme greater than or equal to (\>=) 4 × upper limit of normal (ULN) at time of Screening; Active PM/DM skin rash as per cutaneous dermatomyositis area and severity index-A (CDASI-A) \>= 7 at time of Screening
• Minimum disease severity defined by: moderate to severe myopathy with manual muscle testing-8 (MMT-8) \>= 80 and less than or equal to (\<=) 142 AND at least 2 of the following core set measures (CSM) abnormalities: Patient Global Activity (PtGA) \>= 2 centimeters (cm); Physician Global Activity (PGA) derived from myositis disease activity assessment tool (MDAAT) \>= 2 cm; Extramuscular Activity Assessment derived from MDAAT \>2 cm; At least 1 muscle enzyme \> 1.5 times ULN; health assessment questionnaire-disability index (HAQ-DI) \>= 0.25
• Stable doses of oral corticosteroids (CS) and/or maximum of 1 non-corticosteroid immunosuppressive/immunomodulatory medications (methotrexate, 6 mercaptopurine, sulfasalazine, mycophenolate mofetil or sodium, azathioprine, leflunomide, cyclosporine, oral tacrolimus) for DM or PM
• Participants have a body mass index (BMI) lower or Equal to 40.0 kilograms per square meter (kg/m\^2)

You may not qualify if:

• Primary diagnosis of juvenile DM, or adult participants previously diagnosed with juvenile DM
• Any other active concurrent connective tissue disease associated with inflammatory myopathy in the Investigator's opinion. Eligibility of participants with diagnosis of concurrent connective tissue disease(s) will be reviewed and approved by an idiopathic inflammatory myopathies (IIM) expert committee
• Severe interstitial lung disease defined as supplemental oxygen required at rest, or forced vital capacity (FVC) of \<60 percent (%) predicted. Participants within 1 year of PM/DM diagnosis and anti-MDA5 antibody, should have been evaluated for interstitial lung disease (ILD) with high resolution computed tomography (HRCT) Chest
• Any uncontrolled disease (for example \[e.g.\], severe respiratory, cardiovascular, gastrointestinal, neurological, psychiatric, hematological, metabolic \[including thyroiditis with increased/decreased thyroid stimulating hormone (TSH)\], renal \[Estimated glomerular filtration rate \< 40 milliliter per minute/1.73 m\^2 as calculated by the Modification of Diet in Renal Disease equation by the central laboratory\], hepatic, endocrine/reproductive organ disease) other than DM/PM, that in the Investigator's or Sponsor/designee's opinion constitutes an inappropriate risk or contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (31)

Neuromuscular Research Center

Phoenix, Arizona, 85028, United States

Location

HonorHealth Research Institute - Bob Bove Neuroscience Institute-Neuroscience Research

Scottsdale, Arizona, 85251, United States

Location

Mayo Clinic Scottsdale (6365)

Scottsdale, Arizona, 85259, United States

Location

Barbara Davis Center

Aurora, Colorado, 80045, United States

Location

HMD Research LLC

Orlando, Florida, 32819, United States

Location

Bolanos Clinical Research

Pembroke Pines, Florida, 33026, United States

Location

Augusta University-Rheumatology

Augusta, Georgia, 30912, United States

Location

Johns Hopkins University - Department of Medicine, Division of Rheumatology

Baltimore, Maryland, 21224, United States

Location

University of Minnesota-Dermatology

Minneapolis, Minnesota, 55455, United States

Location

University of Kansas Medical Center-Neuromuscular

Kansas City, Missouri, 66103, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Austin Neuromuscular Center

Austin, Texas, 78759, United States

Location

Nerve and Muscle Center of Texas-Clinical research

Houston, Texas, 77030, United States

Location

Institute of Rheumatology - Rheumatology

Prague, Czechia

Location

Hippokration Hospital - 2nd Department of Medicine and Laboratory

Athens, Greece

Location

National and Kapodistrian University of Athens (Egnitio Hospital)

Athens, Greece

Location

University General Hospital of Larissa

Larissa, Greece

Location

Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco Di Catania (Vittorio Emanuele) - Reumatologia

Catania, Italy

Location

Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania

Catania, Italy

Location

Azienda Usl Toscana Centro

Florence, Italy

Location

Arcispedale S. Maria Nuova

Reggio Emilia, Italy

Location

Fondazione Policlinico Universitario A. Gemelli-IRCCS, UCSC - Scienze Mediche e Chirurgiche

Rome, Italy

Location

Instytut Reumatologii im. Eleonory Reicher - Department of Connective Tissue Diseases

Warsaw, Poland

Location

CHUAC - Complexo Hospitalario Universitario A Coruña - Rheumatology

A Coruña, Spain

Location

Hospital Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario Ramon y Cajal, Madrid - Rheumatology Department

Madrid, Spain

Location

Doncaster Royal Infirmary (3466)

Doncaster, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, United Kingdom

Location

University College London Hospitals NHS Foundation Trust- Neuromuscular Diseases

London, United Kingdom

Location

Salford Royal Hospital, Barnes Clinical Research Facility

Salford, United Kingdom

Location

Royal Wolverhampton Hospitals (6493)

Wolverhampton, United Kingdom

Location

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Dermatomyositis; Polymyositis; Myositis

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Medical Responsible

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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2022
• First Posted: December 14, 2022
• Study Start: January 19, 2023
• Primary Completion: June 25, 2025
• Study Completion: June 25, 2025
• Last Updated: July 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.

Locations

US (13); CZ (1); GR (3); IT (5); ES (3); GB (5); PL (1)