Clinical trial NCT05650567: Study of M5049 in DM and PM Participants (NEPTUNIA)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Dermatomyositis
Polymyositis
Keywords: Toll-like Receptor 7
Toll-like Receptor 8
Anti-synthetase syndrome
Idiopathic immune myopathies
Myositis
M5049
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2022-12-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: DBPC Period: American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Total Improvement Score (TIS) at Week 24
timeFrame: at Week 24
measure: DBPC Period: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)
timeFrame: up to Week 26
measure: DBPC Period: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters, Vital Signs and 12-Lead Electrocardiogram (ECG) Measurements
timeFrame: up to Week 26
Secondary outcomes:
measure: 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
timeFrame: Week 16 and Week 24
measure: DBPC Period: Total Improvement Score (TIS)
timeFrame: Week 4 up to Week 20
measure: DBPC Period: Mean Score for Core Set Measures (CSM) from Week 4 up to Week 24.
timeFrame: Week 4 up to Week 24
measure: DBPC Period: Percent Change from Baseline in Most Abnormal Muscle-associated Enzyme at Weeks 4, 8, 12, 16, 20 and 24
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20 and 24
measure: DBPC Period: Absolute Change from Baseline in the Core Set Measures (CSM) at Weeks 4, 8, 12, 16, 20 and 24'
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20 and 24
measure: DBPC Period: Percent Change from Baseline in Core Set Measures (CSM) at Weeks 4, 8, 12, 16, 20 and 24'
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20 and 24
measure: DBPC Period: Number of Participants with International Myositis Assessment and Clinical Studies (IMACS) Response
timeFrame: Week 16 and Week 24
measure: 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
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20 and 24
measure: 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
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20 and 24
measure: DBPC Period: Change from Baseline in Investigator's Global Assessment (IGA) Skin Activity Score at Weeks 4, 8, 12, 16, 20 and 24
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20 and 24
measure: DBPC Period: Percent Change from Baseline in Investigator's Global Assessment (IGA) Skin Activity Score at Weeks 4, 8, 12, 16, 20 and 24
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20 and 24
measure: OLE Period: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)
timeFrame: up to Week 50
measure: OLE Period: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters, Vital Signs and 12-Lead Electrocardiogram (ECG) Measurements
timeFrame: up to Week 50
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Neuromuscular Research Center
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Research Institute - Bob Bove Neuroscience Institute-Neuroscience Research
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale (6365)
state: Arizona
city: Aurora
country: United States
facility: Barbara Davis Center
state: Colorado
city: Orlando
country: United States
facility: HMD Research LLC
state: Florida
city: Pembroke Pines
country: United States
facility: Bolanos Clinical Research
state: Florida
city: Augusta
country: United States
facility: Augusta University-Rheumatology
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins University - Department of Medicine, Division of Rheumatology
state: Maryland
city: Minneapolis
country: United States
facility: University of Minnesota-Dermatology
state: Minnesota
city: Kansas City
country: United States
facility: University of Kansas Medical Center-Neuromuscular
state: Missouri
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Austin
country: United States
facility: Austin Neuromuscular Center
state: Texas
city: Houston
country: United States
facility: Nerve and Muscle Center of Texas-Clinical research
state: Texas
city: Prague
country: Czechia
facility: Institute of Rheumatology - Rheumatology
city: Athens
country: Greece
facility: Hippokration Hospital - 2nd Department of Medicine and Laboratory
city: Athens
country: Greece
facility: National and Kapodistrian University of Athens (Egnitio Hospital)
city: Larissa
country: Greece
facility: University General Hospital of Larissa
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco Di Catania (Vittorio Emanuele) - Reumatologia
city: Catania
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania
city: Florence
country: Italy
facility: Azienda Usl Toscana Centro
city: Reggio Emilia
country: Italy
facility: Arcispedale S. Maria Nuova
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli-IRCCS, UCSC - Scienze Mediche e Chirurgiche
city: Warszawa
country: Poland
facility: Instytut Reumatologii im. Eleonory Reicher - Department of Connective Tissue Diseases
city: A Coruna
country: Spain
facility: CHUAC - Complexo Hospitalario Universitario A Coruña - Rheumatology
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal, Madrid - Rheumatology Department
city: Doncaster
country: United Kingdom
facility: Doncaster Royal Infirmary (3466)
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust- Neuromuscular Diseases
city: Salford
country: United Kingdom
facility: Salford Royal Hospital, Barnes Clinical Research Facility
city: Wolverhampton
country: United Kingdom
facility: Royal Wolverhampton Hospitals (6493)
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: