A Study of Nipocalimab in Participants With Active Idiopathic Inflammatory Myopathies

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 Nipocalimab versus placebo in participants with active idiopathic inflammatory myopathies (IIM).

Detailed Description
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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.

Official Title
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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

Conditions
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Myositis

Intervention / Treatment
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* Drug: Nipocalimab
* Other: Placebo
* Drug: Glucocorticoids


Participation Criteria
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Eligibility Criteria
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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 (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

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nipocalimab<br>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. | Drug: Nipocalimab<br>* Nipocalimab will be administered intravenously in double-blind period and LTE period.<br>* Other names: JNJ-80202135;Drug: Glucocorticoids<br>* Prednisone or equivalent will be administered orally as Glucocorticoid.<br>|
| Placebo Comparator: Placebo<br>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 continue receiving Nipocalimab matching placebo Q2W starting from Week 52 up to Week 98 and will be followed up to Week 106. | Other: Placebo<br>* Nipocalimab matching placebo will be administered intravenously in double-blind period.<br>Drug: Glucocorticoids<br>* Prednisone or equivalent will be administered orally as Glucocorticoid.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | At Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants who Achieve at Least Minimal Improvement (>=20) in IMACS TIS | IMACS TIS is a standardized clinical response criteria to assess minimal, moderate and major clinical improvement in adult participants with IIM. Minimal improvement is defined as IMACS TIS >=20 in participants with IIM. The criteria use the 6 IMACS core set measures: PhGA, PtGA, MMT-8, muscle enzymes, MDAAT, and 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. | At Week 24 | 
| IMACS TIS | IMACS TIS is a standardized clinical response criteria to assess minimal, moderate and major clinical improvement in adult participants with IIM. The criteria use the 6 IMACS core set measures: PhGA, PtGA, MMT-8, muscle enzymes, MDAAT, and 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. | At Week 52 | 
| Percentage of Participants who Achieve at Least Moderate Improvement (>=40) in IMACS TIS | IMACS TIS is a standardized clinical response criteria to assess minimal, moderate and major clinical improvement in adult participants with IIM. Moderate improvement is defined as IMACS TIS >=40 in participants with IIM. The criteria use the 6 IMACS core set measures: PhGA, PtGA, MMT-8, muscle enzymes, MDAAT, and 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. | At Week 24 | 
| Change From Baseline in Manual Muscle Testing (MMT)-8 at Week 52 | Change from baseline in MMT-8 score at Week 52 will be reported. Manual muscle testing is a partially validated tool to assess muscle strength. It evaluates 8 muscle groups containing 1 axial, 5 proximal, and 2 distal muscle groups. MMT-8 score ranges from 0-150. Higher score indicates greater muscle strength, that is, less impairment of muscle. | Baseline and Week 52 | 
| IMACS TIS | IMACS TIS is a standardized clinical response criteria to assess minimal, moderate and major clinical improvement in adult participants with IIM. The criteria use the 6 IMACS core set measures: PhGA, PtGA, MMT-8, muscle enzymes, MDAAT, and 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. | At Week 24 | 
| Percentage of Participants who Achieve at Least Moderate Improvement (>=40) in IMACS TIS | IMACS TIS is a standardized clinical response criteria to assess minimal, moderate and major clinical improvement in adult participants with IIM. Moderate improvement is defined as IMACS TIS >=40 in participants with IIM. The criteria use the 6 IMACS core set measures: PhGA, PtGA, MMT-8, muscle enzymes, MDAAT, and 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. | At Week 52 | 
| Percentage of Participants who Achieve at Least Major Improvement (>=60) in IMACS TIS | IMACS TIS is a standardized clinical response criteria to assess minimal, moderate and major clinical improvement in adult participants with IIM. Major improvement is defined as IMACS TIS >=60 in participants with IIM. The criteria use the 6 IMACS core set measures: PhGA, PtGA, MMT-8, muscle enzymes, MDAAT and 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. | At Weeks 24 and 52 | 
| Change From Baseline in MMT-8 at Week 24 | Change from baseline in MMT-8 score at Week 24 will be reported. Manual Muscle Testing is a partially validated tool to assess muscle strength. It evaluates 8 muscle groups containing 1 axial, 5 proximal, and 2 distal muscle groups. MMT-8 score ranges from 0-150. Higher score indicates greater muscle strength, that is, less impairment of muscle. | Baseline and Week 24 | 
| Change From Baseline in Physician Global Assessment (PhGA) at Weeks 24 and Week 52 | Change from baseline in PhGA at Weeks 24 and 52 will be reported. Physician Global Activity is a partially validated tool to measure the global evaluation by the physician of the participant's overall disease activity at the time of assessment using a 10 centimeter (cm) visual analogue scale (VAS), where 0 cm= no evidence of disease activity and 10 cm= extremely active or severe disease activity. | Baseline, Weeks 24 and 52 | 
| Change From Baseline in Extramuscular Global Assessment (Myositis Disease Activity Assessment Tool [MDAAT]) at Weeks 24 and 52 | Change from baseline in MDAAT score at Weeks 24 and 52 will be reported. This is a validated tool which measures the degree of disease activity of extramuscular organ systems and muscle. MDAAT is scored on a 10 centimeter (cm) scale ranging from 0-10 cm where, 0 cm = absent and 10 cm = maximum disease activity. Higher score indicates more disease activity. | Baseline, Weeks 24 and 52 | 
| Change From Baseline in Serum Muscle Enzymes Levels at Weeks 24 and 52 | Change from baseline in serum muscle enzymes levels (creatine kinase [CK], alanine aminotransferase [ALT], aspartate aminotransferase [AST], lactate dehydrogenase [LDH], and aldolase) at Weeks 24 and 52 will be reported. | 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 | Percentage of participants who achieve oral GC reduction to 5 mg/day of oral prednisone (or equivalent) at Week 44 and maintain that reduction through Week 52, among participants on oral GC >5 mg/day at baseline will be reported. | 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 | Percentage of participants who achieve at least minimal improvement (>=20) in IMACS TIS from Week 44 through Week 52 and on <=5 mg/day of oral prednisone (or equivalent) from Week 44 through Week 52 will be reported. IMACS TIS is a standardized clinical response criteria to assess minimal, moderate and major clinical improvement in adult participants with IIM. Minimal improvement is defined as IMACS TIS >=20 in participants with IIM. The criteria use the 6 IMACS core set measures: PhGA, PtGA, MMT-8, muscle enzymes, MDAAT, and 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. | From Week 44 through Week 52 | 
| Percentage of Participants on <=5 mg/day of Oral Prednisone (or Equivalent) From Week 44 Through Week 52 | Percentage of participants on <=5 mg/day of oral prednisone (or equivalent) from Week 44 through Week 52 will be reported. | 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 | Percentage of participants who achieve at least minimal improvement (>=20) in IMACS TIS from Week 44 through Week 52 and achieve oral GC reduction to 5 mg/day of prednisone (or equivalent) at Week 44 and maintain that reduction through Week 52, among participants on oral GC >5 mg/day at baseline will be reported. IMACS TIS is a standardized clinical response criteria to assess minimal, moderate and major clinical improvement in adult participants with IIM. Minimal improvement is defined as IMACS TIS >=20 in participants with IIM. The criteria use the 6 IMACS core set measures: PhGA, PtGA, MMT-8, muscle enzymes, MDAAT, and 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. | 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 <=7.5 mg/day of Oral Prednisone (or Equivalent) 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 <=7.5 mg/day of Oral Prednisone (or Equivalent) from Week 44 through Week 52 will be reported. IMACS TIS is a standardized clinical response criteria to assess minimal, moderate and major clinical improvement in adult participants with IIM. Minimal improvement is defined as IMACS TIS >=20 in participants with IIM. The criteria use the 6 IMACS core set measures: PhGA, PtGA, MMT-8, muscle enzymes, MDAAT, and 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. | 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 | 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 will be reported. | 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 | Percentage of participants who achieve at least minimal improvement (>=20) in IMACS TIS from Week 44 through Week 52 and 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 will be reported. IMACS TIS is a standardized clinical response criteria to assess minimal, moderate and major clinical improvement in adult participants with IIM. Minimal improvement is defined as IMACS TIS >=20 in participants with IIM. The criteria use the 6 IMACS core set measures: PhGA, PtGA, MMT-8, muscle enzymes, MDAAT, and 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. | From Week 44 through Week 52 | 
| IMACS TIS Over Time | IMACS TIS is a standardized clinical response criteria to assess minimal, moderate and major clinical improvement in adult participants with IIM. The criteria use the 6 IMACS core set measures: PhGA, PtGA, MMT-8, muscle enzymes, MDAAT, and 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. | Up to 106 weeks | 
| Change From Baseline in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) Scale Score at Weeks 24 and 52 | The CDASI scale is a validated dermatomyositis (DM) specific instrument that systematically quantifies activity and damage in the skin of participant with DM. Disease involvement in 15 different anatomical locations is rated using three activity scales (erythema, scale, erosion/ulceration) and two damage measures (poikiloderma, calcinosis) measures. Gottron's papules/sign on the hands are also evaluated in terms of activity (erythema/ulceration) and damage (dyspigmentation or scarring). Disease activity scores range from 0 to 100. Higher scores indicate greater disease activity. | Baseline, Weeks 24 and 52 | 
| Change in CDASI Scale Score Over Time | The CDASI scale is a validated DM specific instrument that systematically quantifies activity and damage in the skin of participant with DM. Disease involvement in 15 different anatomical locations is rated using three activity scales (erythema, scale, erosion/ulceration) and two damage measures (poikiloderma, calcinosis) measures. Gottron's papules/sign on the hands are also evaluated in terms of activity (erythema/ulceration) and damage (dyspigmentation or scarring). Disease activity scores range from 0 to 100. Higher scores indicate greater disease activity. | Up to 106 Weeks | 
| Percentage of Participants With Treatment-Emergent Adverse Events (AEs) | Any AE occurring at or after the initial administration of study intervention through the safety follow-up visit will be considered as treatment-emergent. An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product that does not necessarily have a causal relationship with the intervention. | Up to 106 weeks | 
| Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) | Any AE occurring at or after the initial administration of study intervention through the safety follow-up visit will be considered as treatment-emergent. An SAE is any untoward medical occurrence that at any dose: results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via a medicinal product; is medically important. | Up to 106 weeks | 
| Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS)- Physical Function (PF)-20 | PROMIS-PF-20 is a participant self-administered 20-item questionnaire assessing the physical function domain. It includes 14 items regarding patients' ability to conduct specific functional activities and 6 items regarding the extent to which their health limits their ability to perform a range of physical activities currently. The 5-point response options for the former items range from 1 Unable to do to 5 Without any difficulty and the latter items range from 1 Cannot do to 5 Not at all with higher scores indicating better functioning. The overall score ranges from 0 to 100, where higher score indicates better physical function. | Baseline and Week 52 | 
| Change From Baseline in Functional Disability Using the Health Assessment Questionnaire-disability Index (HAQ-DI) | HAQ-DI score assess functional status of participant. It is 20 question instrument that assess degree of functional disability a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and common activities of daily living). Responses in each functional area are scored from 0=indicating no difficulty, to 3=indicating inability to perform a task in that area. Total HAQ score is average of the computed categories scores ranging from 0-3 where 0=least difficulty and 3=extreme difficulty. Lower scores are indicative of better functioning. | Baseline, Weeks 24 and 52 | 
| Serum Nipocalimab Concentration Over Time | Serum nipocalimab concentration over time will be reported. Serum nipocalimab concentration will be derived using population pharmacokinetic (PK) modeling. | Baseline Up to Week 98 | 
| Number of Participants With Anti-drug Antibody (ADA) Measured Using a Validated, Specific, and Sensitive Immunoassay Method | Number of participants with ADA to Nipocalimab measured using a validated, specific, and sensitive immunoassay method will be reported. | Baseline Up to Week 106 | 
| Number of Participants With Neutralizing Antibodies (Nabs) to Nipocalimab Measured Using a Validated, Specific, and Sensitive Immunoassay Method | Number of participants with Nabs to Nipocalimab measured using a validated, specific, and sensitive immunoassay method will be reported. | Baseline Up to Week 106 |