Study of M5049 in DM and PM Participants (NEPTUNIA)

NCT05650567 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: MS200569_00412022-501351-82-00
• Study Type: interventional
• Target: 20
• 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 (5)

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

  The ACR/EULAR TIS was derived from evaluation of results from 6 Core Set Measures(CSMs) of myositis disease activity in participants with Dermatomyositis and Polymyositis.TIS was determined by summing scores for each CSM,based on improvement in absolute percent change which is calculated by subtracting the baseline value from the final value,dividing difference by the range, and then multiplying the result by100 and relative weight of each core set measure. The TIS scale ranges from 0 to 100 with thresholds for minimal \[more than or equal to(\>= 20)\],moderate(\>= 40) and major(\>= 60)improvement in combined 6 CSM.The CSMs include,physician global activity visual analogue scale(VAS) score(0-10), patient global activity VAS score(0-10), manual muscle testing-8 score(0-150), health assessment questionnaire-disability index(0-3) along with checks for most abnormal muscle-associated enzymes and extra muscular activity assessment derived using myositis disease activity assessment tool(0-10).

  At Week 24 (end of DBPC period)

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

  An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether considered related to the medicinal product or protocol-specified procedure. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious TEAEs and non-serious TEAEs. Adverse events of special interest (AESI) are serious or non-serious AEs that are of clinical interest and were closely followed.

  Up to Week 26 (Safety follow up)

• DBPC Period: Number of Participants With Clinically Meaningful Changes From Baseline in Laboratory Parameters

  Laboratory parameters included hematology, biochemistry, urinalysis and reflex testing for HBV DNA. Number of participants with clinically meaningful changes from baseline in laboratory parameters were reported. Clinical meaningfulness was assessed by the investigator.

  Up to Week 26 (Safety follow up)

• DBPC Period: Number of Participants With Clinically Meaningful Changes From Baseline in Vital Signs

  Vital signs included body temperature, systolic and diastolic blood pressure, respiration rate, pulse rate, weight, height and body mass index. Number of participants with clinically meaningful changes from baseline in vital signs were reported. Clinical meaningfulness was assessed by the investigator.

  Up to Week 26 (Safety follow up)

• DBPC Period: Number of Participants With Clinically Meaningful Changes From Baseline in Electrocardiograms (ECG) Parameters

  12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. Number of participants with clinically meaningful changes from baseline in ECG parameters were reported. Clinical meaningfulness was assessed by the investigator.

  Up to Week 26 (Safety follow up)

Secondary Outcomes (15)

• 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

  At Week 16 and Week 24

• DBPC Period: Participant's Total Improvement Score (TIS)

  Week 4, 8, 12, 16, 20 and 24

• DBPC Period: Change From Baseline in Physician Global Activity (PGA) Scores From Myositis Disease Activity Assessment Tool (MDAAT)

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

• DBPC Period: Change From Baseline in Patient Global Activity (PtGA) Visual Analog Scale (VAS) Score

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

• DBPC Period: Change From Baseline in Extra Muscular Global Assessment From Myositis Disease Activity Assessment Tool (MDAAT) Score

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

Study Arms (3)

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

EXPERIMENTAL

Drug: M5049 dose

DBPC Period: Placebo

PLACEBO COMPARATOR

Drug: Placebo

Open Label Extension (OLE) Period: M5049 dose

EXPERIMENTAL

Drug: M5049 dose

Interventions

Placebo DRUG

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

DBPC Period: Placebo

M5049 dose DRUG

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

Also known as: Enpatoran

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

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

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

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: September 9, 2026
• Results First Posted: September 9, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: IPD from completed trials will be publicly available within 6 months after all of the following events: * Approval of a product/new indication by major authorities (FDA, EMA, PMDA if requested) with no pending submissions * Public results via primary manuscript or trial registry disclosure * Legal authority to share data * Privacy protections are in place If approval is not sought or development is globally discontinued, data will be publicly available within 18 months after global trial completion. Further information on how to request data can be found on our website bit.ly/IPD21
• Access Criteria: Qualified researchers may propose access to IPD from sponsored trials via https://vivli.org/members/ourmembers/.

Locations

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