Study of M5049 in DM and PM Participants (NEPTUNIA)

Dermatomyositis Clinical Trial

Official title:

A Phase IIa, Randomized, Parallel, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Enpatoran in Dermatomyositis and Polymyositis Participants Receiving Standard of Care (NEPTUNIA)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05650567
• Other study ID #: MS200569_0041
• Secondary ID: 2022-501351-82-0
• Status: Recruiting
• Phase: Phase 2
• Start date: January 19, 2023
• Est. completion date: December 4, 2024

Study information

• Verified date: May 2024
• Source: EMD Serono
• Contact: US Medical Information
• Phone: 888-275-7376
• Email: eMediUSA[@]emdserono.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 4, 2024
• Est. primary completion date: July 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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)

• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Primary diagnosis of inclusion body myositis (IBM), malignancy-associated myositis (defined as diagnosis of myositis within 3 years of cancer), immune mediated necrotizing myopathy (IMNM) with a biopsy characterized as necrotizing biopsy or IMNM with positive anti-signal recognition particle antibody (SRP) or anti 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) auto antibodies. Participants with anti-transcription intermediary factor 1 (TIF1) gamma antibody or newly diagnosed (within 1 year) anti MDAT5 antibody should have had adequate screening for cancer within 12 months of Day 1. Adequate screening of cancer is defined as up-to-date age and gender appropriate screening as per national guidelines

• 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

• Other protocol defined exclusion criteria could apply

Related Conditions & MeSH terms

• Dermatomyositis
• Polymyositis

Intervention

Drug:
• M5049 high dose
Participants will receive film-coated tablets of M5049 at a high dose orally, twice daily up to 24 weeks.
• Placebo
Participants will receive placebo matched to M5049 orally, twice daily up to 24 weeks.

Locations

Country	Name	City	State
Czechia	Institute of Rheumatology - Rheumatology	Prague
Greece	Hippokration Hospital - 2nd Department of Medicine and Laboratory	Athens
Greece	National and Kapodistrian University of Athens (Egnitio Hospital)	Athens
Greece	University General Hospital of Larissa	Larissa
Italy	Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania	Catania
Italy	Azienda Usl Toscana Centro	Florence
Italy	Arcispedale S. Maria Nuova	Reggio Emilia
Italy	Fondazione Policlinico Universitario A. Gemelli-IRCCS, UCSC - Scienze Mediche e Chirurgiche	Rome
Poland	Instytut Reumatologii im. Eleonory Reicher - Department of Connective Tissue Diseases	Warszawa
Spain	CHUAC - Complexo Hospitalario Universitario A Coruña - Rheumatology	A Coruna
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Universitario Ramon y Cajal, Madrid - Rheumatology Department	Madrid
United Kingdom	University College London Hospitals NHS Foundation Trust- Neuromuscular Diseases	London
United Kingdom	Salford Royal Hospital, Barnes Clinical Research Facility	Salford
United States	Augusta University-Rheumatology	Augusta	Georgia
United States	Austin Neuromuscular Center	Austin	Texas
United States	Johns Hopkins University - Department of Medicine, Division of Rheumatology	Baltimore	Maryland
United States	Nerve and Muscle Center of Texas-Clinical research	Houston	Texas
United States	University of Kansas Medical Center-Neuromuscular	Kansas City	Missouri
United States	University of Minnesota-Dermatology	Minneapolis	Minnesota
United States	HMD Research LLC	Orlando	Florida
United States	Neuromuscular Research Center	Phoenix	Arizona
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	HonorHealth Research Institute - Bob Bove Neuroscience Institute-Neuroscience Research	Scottsdale	Arizona
United States	Mayo Clinic Scottsdale (6365)	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  Czechia,  Greece,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DBPC Period: American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Total Improvement Score (TIS) at Week 24		at Week 24
Primary	DBPC Period: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)		up to Week 26
Primary	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	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
Secondary	DBPC Period: Total Improvement Score (TIS)		Week 4 up to Week 20
Secondary	DBPC Period: Mean Score for Core Set Measures (CSM) from Week 4 up to Week 24.		Week 4 up to Week 24
Secondary	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
Secondary	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
Secondary	DBPC Period: Percent Change from Baseline in Core Set Measures (CSM) at Weeks 4, 8, 12, 16, 20 and 24'		Baseline, Weeks 4, 8, 12, 16, 20 and 24
Secondary	DBPC Period: Number of Participants with International Myositis Assessment and Clinical Studies (IMACS) Response		Week 16 and Week 24
Secondary	DBPC Period: Change from Baseline in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) A and CDASI-D at Weeks 4, 8, 12, 16, 20 and 24		Baseline, Weeks 4, 8, 12, 16, 20 and 24
Secondary	DBPC Period: Percent Change from Baseline in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) A and CDASI-D at Weeks 4, 8, 12, 16, 20 and 24		Baseline, Weeks 4, 8, 12, 16, 20 and 24
Secondary	DBPC Period: Change from Baseline in Investigator's Global Assessment (IGA) Skin Activity Score at Weeks 4, 8, 12, 16, 20 and 24		Baseline, Weeks 4, 8, 12, 16, 20 and 24
Secondary	DBPC Period: Percent Change from Baseline in Investigator's Global Assessment (IGA) Skin Activity Score at Weeks 4, 8, 12, 16, 20 and 24		Baseline, Weeks 4, 8, 12, 16, 20 and 24
Secondary	OLE Period: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)		up to Week 50
Secondary	OLE Period: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters, Vital Signs and 12-Lead Electrocardiogram (ECG) Measurements		up to Week 50

External Links

•   Trial Awareness and Transparency website