Overview
The purpose of this study is to evaluate the efficacy and safety of Nipocalimab versus placebo in participants with active idiopathic inflammatory myopathies (IIM).
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.
Eligibility
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), antinuclear 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
