Study of M5049 in DM and PM Participants (NEPTUNIA)

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Dermatomyositis, Polymyositis

Intervention / Treatment
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* Drug: M5049 high dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Double-blind Placebo Controlled (DBPC) Period: M5049 high dose<br> | Drug: M5049 high dose<br>* Participants will receive film-coated tablets of M5049 at a high dose orally, twice daily up to 24 weeks.<br>* Other names: Enpatoran;|
| Placebo Comparator: DBPC Period: Placebo<br> | Drug: Placebo<br>* Participants will receive placebo matched to M5049 orally, twice daily up to 24 weeks.<br>|
| Experimental: Open Label Extension (OLE) Period: M5049 high dose<br> | Drug: M5049 high dose<br>* Participants will receive film-coated tablets of M5049 at a high dose orally, twice daily up to 24 weeks.<br>* Other names: Enpatoran;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| DBPC Period: Number of Participants with International Myositis Assessment and Clinical Studies (IMACS) Response |  | Week 16 and Week 24 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| OLE Period: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs) |  | up to Week 50 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Toll-like Receptor 7, Toll-like Receptor 8, Anti-synthetase syndrome, Idiopathic immune myopathies, Myositis, M5049