A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Nipocalimab in Participants With Active Idiopathic Inflammatory Myopathies
Overview
- Phase
- Phase 2
- Intervention
- Glucocorticoids
- Conditions
- Myositis
- Sponsor
- Janssen Research & Development, LLC
- Enrollment
- 36
- Locations
- 101
- Primary Endpoint
- Percentage of Participants who Achieve at Least Minimal Improvement (Greater Than or Equal to [>=] 20) in IMACS TIS and on Less Than or Equal to (<=) 5 Milligrams per day (mg/day) of Oral Prednisone (or Equivalent) From Week 44 Through Week 52
- Status
- Active, not recruiting
- Last Updated
- 19 days ago
Overview
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of Nipocalimab versus placebo in participants with active idiopathic inflammatory myopathies (IIM).
Detailed Description
IIM is considered as a group of rare diseases that is characterized by common features of insidious painless, proximal skeletal muscle weakness, low endurance, and elevated serum muscle enzyme levels. Due to muscle weakness and progressive muscular atrophy, decreasing endurance, internal organ involvement (mainly given the pulmonary, gastrointestinal and cardiac manifestations) and limited therapeutic options, IIM often leads to physical disability and decreased quality of life. Nipocalimab is a fully human aglycosylated immunoglobulin G1 (IgG1) monoclonal antibody (mAb) designed to selectively bind, saturate, and block the immunoglobulin G (IgG) binding site on the endogenous neonatal fragment crystallizable receptor (FcRn) that binds, salvages, and recycles IgG into circulation or transport IgG across the placenta, following nonspecific pinocytosis into endothelial cells and cells of the reticuloendothelial system. At homeostasis, FcRn recycles IgG to maintain serum IgG levels and extend IgG half-life and also regulates immune cell inflammatory responses to IgG complexes. By targeting the IgG binding site on FcRn, nipocalimab is expected to block the binding and, hence, recycling of IgG, resulting in a decrease in circulating IgG antibody levels, including pathogenic IgG autoantibodies and alloantibodies. Therefore, nipocalimab has potential in the treatment of active IIM by decreasing pathogenic IgG antibody concentrations. The total duration of the study is up to 112 weeks, consisting of 4 study periods: a less than or equal to (\<=) 6-week screening period, a 52-week double-blind period, a 48-week long term extension (LTE), and a safety follow-up 8 weeks post last administration of study intervention. Safety assessments include adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs), laboratory parameters (hematology and chemistry, including lipid panel), vital signs, and physical examination.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Disease classification criteria: Participant meets the diagnostic criteria of probable or definite idiopathic inflammatory myopathies (IIM) based on 2017 The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for adult IIM at least 6 weeks prior to first administration of the study intervention
- •If a participant is on regular or as needed treatment with low potency topical glucocorticoids (GC) that are allowed in the study or topical tacrolimus (TAC) to treat skin lesions, the dose and frequency should be stable for greater than or equal to (\>=) 4 weeks prior to first administration of the study intervention as well as maintained at the same dose until Week 52 of the study
- •Antibody positivity criteria: Any 1 of the myositis-specific antibodies (MSAs) positive: dermatomyositis (DM): anti-Mi-2 (Mi-2/nucleosome remodeling and deacetylase \[NuRD\] complex), anti-transcription intermediary factor 1-Gamma (TIF1-Gamma), anti- nuclear matrix protein 2 (NXP-2), anti-small ubiquitin-like modifier-1 activating enzyme; anti- antimelanoma differentiation-associated gene 5 (MDA-5) antibodies. Or immune-mediated necrotizing myopathy (IMNM): anti- signal recognition particle (SRP) and anti- 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies. Or anti-synthetase syndrome (ASyS): anti- histidyl- ribonucleic acid \[tRNA\] synthetase (Jo-1), anti- threonyl-tRNA synthetase (PL7), anti- alanyl-tRNA synthetase (PL12), anti- isoleucyl-tRNA synthetase (OJ), and anti- glycyl-tRNA synthetase (EJ) antibodies. If all MSAs are negative or more than 1 MSA is positive within different subtypes (defined by the central laboratory) at screening, the tests should be repeated during the screening period. If the same results are observed at retesting, the participant should not be enrolled in the study
Exclusion Criteria
- •Has a juvenile myositis diagnosis and now \>=18 years old
- •Has cancer-associated myositis defined as cancer diagnosis within 3 years of myositis diagnosis except for cervical carcinoma in situ and non-melanoma skin cancer (squamous cell carcinoma, basal cell carcinoma of the skin)
- •Has comorbidities (example, asthma, chronic obstructive pulmonary disease \[COPD\]) which have required 3 or more courses of oral GC within 1 year prior to screening
- •Has a history of primary immunodeficiency or secondary immunodeficiency not related to the treatment of the participants IIM
- •Has experienced myocardial infarction (MI), unstable ischemic heart disease, or stroke within 12 weeks of screening
Arms & Interventions
Nipocalimab
Participants will receive Nipocalimab at Week 0 (Baseline) and then every 2 weeks (Q2W) up to Week 50 during double-blind period. Participants on glucocorticoids (GC) at baseline will receive a stable dose of oral GC (prednisone or equivalent) from 4 weeks prior to the first administration of study intervention to Week 0. No changes in GC doses are allowed between Week 0 and Week 24. From Week 24 to Week 44, GC doses will be tapered. No changes to GC doses will be allowed from Week 44 to Week 52. Eligible participants will enter long-term extension (LTE) period and continue receiving Nipocalimab starting from Week 52 up to Week 98 and will be followed up to Week 106.
Intervention: Glucocorticoids
Placebo
Participants will receive Nipocalimab matching placebo at Week 0 (Baseline) and then Q2W up to Week 50 during double-blind period. Participants on GC at baseline will receive a stable dose of oral GC (prednisone or equivalent) from 4 weeks prior to the first administration of study intervention to Week 0. No changes in GC doses are allowed between Week 0 and Week 24. From Week 24 to Week 44, GC doses will be tapered. No changes to GC doses will be allowed from Week 44 to Week 52. Eligible participants will enter LTE period and will receive Nipocalimab treatment Q2W starting from Week 52 up to Week 98 and will be followed up to Week 106.
Intervention: Placebo
Placebo
Participants will receive Nipocalimab matching placebo at Week 0 (Baseline) and then Q2W up to Week 50 during double-blind period. Participants on GC at baseline will receive a stable dose of oral GC (prednisone or equivalent) from 4 weeks prior to the first administration of study intervention to Week 0. No changes in GC doses are allowed between Week 0 and Week 24. From Week 24 to Week 44, GC doses will be tapered. No changes to GC doses will be allowed from Week 44 to Week 52. Eligible participants will enter LTE period and will receive Nipocalimab treatment Q2W starting from Week 52 up to Week 98 and will be followed up to Week 106.
Intervention: Glucocorticoids
Nipocalimab
Participants will receive Nipocalimab at Week 0 (Baseline) and then every 2 weeks (Q2W) up to Week 50 during double-blind period. Participants on glucocorticoids (GC) at baseline will receive a stable dose of oral GC (prednisone or equivalent) from 4 weeks prior to the first administration of study intervention to Week 0. No changes in GC doses are allowed between Week 0 and Week 24. From Week 24 to Week 44, GC doses will be tapered. No changes to GC doses will be allowed from Week 44 to Week 52. Eligible participants will enter long-term extension (LTE) period and continue receiving Nipocalimab starting from Week 52 up to Week 98 and will be followed up to Week 106.
Intervention: Nipocalimab
Outcomes
Primary Outcomes
Percentage of Participants who Achieve at Least Minimal Improvement (Greater Than or Equal to [>=] 20) in IMACS TIS and on Less Than or Equal to (<=) 5 Milligrams per day (mg/day) of Oral Prednisone (or Equivalent) From Week 44 Through Week 52
Time Frame: At Week 52
Percentage of participants who achieve at least minimal improvement (\>=20) in IMACS TIS at Week 52 and on \<=5 mg/day of oral prednisone (or equivalent) from Week 44 through Week 52 will be reported. International Myositis Assessment and Clinical Studies Total Improvement Score (IMACS TIS) is a standardized clinical response criteria to assess minimal, moderate and major clinical improvement in adult participants with idiopathic inflammatory myopathies (IIM). Minimal improvement is defined as IMACS TIS greater than or equal to (\>=) 20 in participants with IIM. The criteria use the 6 IMACS core set measures: physicians' global activity, patient global activity (PtGA), manual muscle testing (MMT)-8, muscle enzymes, myositis disease activity assessment tool (MDAAT), and health assessment questionnaire-disability index (HAQ-DI). The absolute percentage change in each measure with varying weights is combined to obtain a TIS on a scale of 0 to 100. Higher score indicates greater improvement.
Secondary Outcomes
- Percentage of Participants who Achieve at Least Major Improvement (>=60) in IMACS TIS(At Weeks 24 and 52)
- Change From Baseline in Extramuscular Global Assessment (Myositis Disease Activity Assessment Tool [MDAAT]) at Weeks 24 and 52(Baseline, Weeks 24 and 52)
- Percentage of Participants who Achieve Oral Glucocorticoids (GC) Reduction to 5 Milligrams per day (mg/day) of Oral Prednisone (or Equivalent), Among Participants on Oral GC Greater Than (>) 5 mg/day at Baseline(From Week 44 through Week 52)
- Percentage of Participants who Achieve at Least Minimal Improvement (>=20) in IMACS TIS From Week 44 Through Week 52 and on Less Than or Equal to (<=) 5 mg/day of Oral Prednisone (or Equivalent) From Week 44 Through Week 52(From Week 44 through Week 52)
- Percentage of Participants on <=5 mg/day of Oral Prednisone (or Equivalent) From Week 44 Through Week 52(From Week 44 through Week 52)
- Percentage of Participants who Achieve At Least Minimal Improvement (>=20) in IMACS TIS and Achieve Oral GC Reduction to 5 mg/day at Week 44 and Maintain That Reduction Through Week 52, Among Participants on Oral GC >5 mg/day at Baseline(From Week 44 through Week 52)
- IMACS TIS Over Time(Up to 106 weeks)
- Percentage of Participants who Achieve at Least Minimal Improvement (>=20) in IMACS TIS(At Week 24)
- IMACS TIS(At Week 24)
- Percentage of Participants who Achieve at Least Moderate Improvement (>=40) in IMACS TIS(At Week 52)
- Change From Baseline in Manual Muscle Testing (MMT)-8 at Week 52(Baseline and Week 52)
- Change From Baseline in MMT-8 at Week 24(Baseline and Week 24)
- Change From Baseline in Physician Global Assessment (PhGA) at Weeks 24 and Week 52(Baseline, Weeks 24 and 52)
- Change From Baseline in Serum Muscle Enzymes Levels at Weeks 24 and 52(Baseline, Weeks 24 and 52)
- Percentage of Participants who Achieve at Least Minimal Improvement (>=20) in IMACS TIS From Week 44 Through Week 52 and on <=7.5 mg/day of Oral Prednisone (or Equivalent) From Week 44 Through Week 52(From Week 44 through Week 52)
- Percentage of Participants who Achieve Oral GC Reduction to <=7.5 mg/day of Oral Prednisone (or Equivalent) at Week 44 and Maintain That Reduction Through Week 52, Among Participants on Oral GC >7.5 mg/day at Baseline(At Week 44 through Week 52)
- Percentage of Participants who Achieve at Least Minimal Improvement (>=20) in IMACS TIS and Achieve Oral GC Reduction to <=7.5 mg/day at Week 44 and Maintain That Reduction Through Week 52, Among Participants on Oral GC >7.5 mg/day at Baseline(From Week 44 through Week 52)
- Change From Baseline in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) Scale Score at Weeks 24 and 52(Baseline, Weeks 24 and 52)
- Change in CDASI Scale Score Over Time(Up to 106 Weeks)
- Percentage of Participants With Treatment-Emergent Adverse Events (AEs)(Up to 106 weeks)
- Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)(Up to 106 weeks)
- Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS)- Physical Function (PF)-20(Baseline and Week 52)
- Change From Baseline in Functional Disability Using the Health Assessment Questionnaire-disability Index (HAQ-DI)(Baseline, Weeks 24 and 52)
- Serum Nipocalimab Concentration Over Time(Baseline Up to Week 98)
- Number of Participants With Anti-drug Antibody (ADA) Measured Using a Validated, Specific, and Sensitive Immunoassay Method(Baseline Up to Week 106)
- Number of Participants With Neutralizing Antibodies (Nabs) to Nipocalimab Measured Using a Validated, Specific, and Sensitive Immunoassay Method(Baseline Up to Week 106)
- IMACS TIS(At Week 52)
- Percentage of Participants who Achieve at Least Moderate Improvement (>=40) in IMACS TIS(At Week 24)