Study of M5049 in DM and PM Participants (NEPTUNIA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Healthcare KGaA

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Immune System Diseases [C20], Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

23 May 2023 → 25 Jun 2025

Decision date (initial)

2023-04-21

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Merck Healthcare KGaA

External identifiers

EU CT number

2022-501351-82-00

ClinicalTrials.gov

NCT05650567

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

(1) To evaluate the effect of enpatoran compared to placebo on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Total Improvement Score (TIS) at Week 24 of the Double-Blind Placebo Controlled (DBPC) period in DM and PM participants
(2) To evaluate the safety and tolerability of enpatoran in DM and PM participants during the DBPC period

Secondary objectives 1

1. (1) To evaluate the efficacy in disease control with enpatoran compared to placebo in DM and PM participants during the DBPC period (2) To evaluate the efficacy on cutaneous disease activity of DM (in DM participants and PM participants with rash, defined as Cutaneous Dermatomyositis Disease Area and Severity Index [CDASI]-A≥ 7) with enpatoran compared to placebo during the DBPC period (3) To evaluate the safety and tolerability of enpatoran in DM and PM participants during the Open Label Extension (OLE) period

Conditions and MedDRA coding

Dermatomyositis, Polymyositis

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 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
2. Active disease on standard of care (SoC), must meet one 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
3. 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 one muscle enzyme > 1.5 times ULN; health assessment questionnaire-disability index (HAQ-DI) >= 0.25
4. 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
5. Participants have a body mass index (BMI) lower or Equal to 40.0 kilograms per square meter (kg/m^2)
6. Other protocol defined inclusion criteria could apply

Exclusion criteria 6

1. 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
2. Primary diagnosis of juvenile DM, or adult participants previously diagnosed with juvenile DM
3. 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
4. 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.
5. 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
6. Other protocol defined exclusion criteria could apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. DBPC Period: American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Total Improvement Score (TIS) at Week 24
2. DBPC Period: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)
3. DBPC Period: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters, Vital Signs and 12-Lead Electrocardiogram (ECG) Measurements

Secondary endpoints 13

1. 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
2. DBPC Period: Total Improvement Score (TIS)
3. DBPC Period: Mean Score for Core Set Measures (CSM) from Week 4 up to Week 24
4. DBPC Period: Percent Change from Baseline in Most Abnormal Muscle-associated Enzyme at Weeks 4, 8, 12, 16, 20 and 24
5. DBPC Period: Absolute Change from Baseline in the Core Set Measures (CSM) at Weeks 4, 8, 12, 16, 20 and 24
6. DBPC Period: Percent Change from Baseline in Core Set Measures (CSM) at Weeks 4, 8, 12, 16, 20 and 24
7. DBPC Period: Number of Participants with International Myositis Assessment and Clinical Studies (IMACS) Response
8. 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
9. 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
10. DBPC Period: Change from Baseline in Investigator’s Global Assessment (IGA) Skin Activity Score at Weeks 4, 8, 12, 16, 20 and 24
11. DBPC Period: Percent Change from Baseline in Investigator’s Global Assessment (IGA) Skin Activity Score at Weeks 4, 8, 12, 16, 20 and 24
12. OLE Period: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)
13. OLE Period: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters, Vital Signs and 12-Lead Electrocardiogram (ECG) Measurements

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Healthcare KGaA

Sponsor organisation

Merck Healthcare KGaA

Address

Frankfurter Strasse 250

City

Darmstadt

Postcode

64293

Country

Germany

Scientific contact point

Organisation

Merck Healthcare KGaA

Contact name

Global Regulatory Affairs

Public contact point

Organisation

Merck Healthcare KGaA

Contact name

Global Regulatory Affairs

Third parties 10

Locations

6 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 218 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications