Study of M5049 in DM and PM Participants (NEPTUNIA)

• ClinicalTrials.gov Identifier: NCT05650567
• Recruitment Status: Recruiting
• First Posted: December 14, 2022
• Last Update Posted: May 14, 2024
• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborator: Merck KGaA, Darmstadt, Germany
• Information provided by (Responsible Party): EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Tracking Information

• First Submitted Date: December 6, 2022
• First Posted Date: December 14, 2022
• Last Update Posted Date: May 14, 2024
• Actual Study Start Date: January 19, 2023
• Estimated Primary Completion Date: July 16, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 6, 2022)

• DBPC Period: American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Total Improvement Score (TIS) at Week 24 [ Time Frame: at Week 24 ]
• DBPC Period: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs) [ Time Frame: 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 [ Time Frame: up to Week 26 ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 6, 2022)

• 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 [ Time Frame: Week 16 and Week 24 ]
• DBPC Period: Total Improvement Score (TIS) [ Time Frame: Week 4 up to Week 20 ]
• DBPC Period: Mean Score for Core Set Measures (CSM) from Week 4 up to Week 24. [ Time Frame: 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 [ Time Frame: 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' [ Time Frame: 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' [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24 ]
• DBPC Period: Number of Participants with International Myositis Assessment and Clinical Studies (IMACS) Response [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: up to Week 50 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• 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.
  Other Name: Enpatoran
• Drug: Placebo
  Participants will receive placebo matched to M5049 orally, twice daily up to 24 weeks.

Study Arms

• Experimental: Double-blind Placebo Controlled (DBPC) Period: M5049 high dose
  Intervention: Drug: M5049 high dose
• Placebo Comparator: DBPC Period: Placebo
  Intervention: Drug: Placebo
• Experimental: Open Label Extension (OLE) Period: M5049 high dose
  Intervention: Drug: M5049 high dose

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 6, 2022): 40
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 4, 2024
• Estimated Primary Completion Date: July 16, 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: US Medical Information; 888-275-7376; eMediUSA@emdserono.com

Contact: Communication Center; +49 6151 72 5200; service@emdgroup.com

• Listed Location Countries: Czechia, Greece, Italy, Poland, Spain, United Kingdom, United States
• Removed Location Countries: Germany

Administrative Information

• NCT Number: NCT05650567
• Other Study ID Numbers: MS200569_0041; 2022-501351-82-00 ( Other Identifier: EUCT number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: 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.
• URL: https://bit.ly/IPD21

• Current Responsible Party: EMD Serono ( EMD Serono Research & Development Institute, Inc. )
• Original Responsible Party: Same as current
• Current Study Sponsor: EMD Serono Research & Development Institute, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible; Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

• PRS Account: EMD Serono
• Verification Date: May 2024