Efficacy and Safety Study of Nipocalimab for Adults With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety and efficacy of nipocalimab compared to placebo in delaying relapse in adults with chronic inflammatory demyelinating polyneuropathy (CIDP) who initially respond to nipocalimab in Stage A.

Detailed Description
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CIDP is a rare, chronic autoimmune disease of the peripheral nervous system characterized by progressive weakness and impaired sensation. Nipocalimab (also referred to as JNJ-80202135 or M281) is a fully human aglycosylated immunoglobulin (Ig)G1 monoclonal antibody (mAb) designed to selectively bind, saturate, and block the IgG binding site on the endogenous neonatal Fc receptor. The study will consist of the following periods: (a) identification of participants with active CIDP (including screening [up to 4 weeks] and run-in [up to 12 weeks]); (b) open-label treatment with nipocalimab (Stage A) (12 weeks); (c) double-blind, placebo-controlled, randomized withdrawal (Stage B) (up to 52 weeks); and (d) an open-label extension (OLE) (until to 2 years after marketing authorization in the participant's local country or until nipocalimab becomes available commercially or via other continued access program, whichever comes first). Participants who discontinue treatment and intend to withdraw from the study at any point during the treatment periods (Stage A, Stage B, or the OLE) will be requested to enter an 8-weeks follow-up after the last dose of study intervention. Efficacy, safety, pharmacokinetics (PK), immunogenicity, and biomarker evaluations will be assessed.

Official Title
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Phase 2/3, Multistage, Multicenter, Randomized, Double-Blind, Placebo-Controlled Parallel Group Withdrawal Study to Evaluate the Efficacy and Safety of Nipocalimab Administered to Adults With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Conditions
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Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Intervention / Treatment
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* Drug: Nipocalimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults greater than or equal to (>=) 18 years of age at the time of consent and as applicable, must also meet the legal age of consent in the jurisdiction in which the study is taking place Diagnosed with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) according to criteria of the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) 2021, progressing or relapsing forms. CIDP diagnosis to be adjudicated by independent committee during screening period Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score between 2 and 9 (a score of 2 has to be exclusively from leg disability) Fulfilling any of the following treatment conditions: a) Currently treated with pulsed corticosteroids, oral corticosteroids and/or intravenous immunoglobulin (IVIg) or subcutaneous immunoglobulin (SCIg) and the participant is willing to discontinue or taper this treatment at the first run-in visit; or b) Without previous treatment (treatment naive); or treatment with corticosteroids and/or IVIg or SCIg discontinued at least 3 months prior to screening (untreated) Active disease as determined by CIDP Disease Activity Status (CDAS) score >= 3 Other protocol-defined inclusion criteria will apply Exclusion Criteria: Has a history of severe and/or uncontrolled hepatic (example, viral/alcoholic/autoimmune hepatitis/cirrhosis and/or metabolic liver disease), gastrointestinal, renal, pulmonary, cardiovascular, psychiatric, neurological or musculoskeletal disorder, hypertension and/or any other medical or uncontrolled autoimmune disorder(s) (example, diabetes mellitus) or clinically significant abnormalities in screening laboratory that, might interfere with the participants full participation in the study, or might jeopardize the safety of the participant or the validity of the study results Pure sensory CIDP or chronic immune sensory polyradiculopathy (CISP) (EAN/PNS definition) Any other disease that could better explain the participant's signs and symptoms, such as significant persisting neurological deficits from stroke or central nervous system (CNS) trauma or peripheral neuropathy from another cause such as connective tissue disease or systemic lupus erythematosus Polyneuropathy of other causes, including the following: Multifocal motor neuropathy (MMN); Monoclonal gammopathy of uncertain significance with antimyelin associated glycoprotein (anti-MAG) immunoglobulin M (IgM) antibodies; Hereditary motor neuropathy; Hereditary neuropathy with liability to pressure palsies (HNPP); Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin change syndromes; Lumbosacral radiculoplexus neuropathy; Polyneuropathy most likely due to diabetes mellitus; Polyneuropathy most likely due to systemic illnesses; Drug- or toxin-induced polyneuropathy Note: A concomitant polyneuropathy of other causes (example, a mild, stable diabetic polyneuropathy) is not necessarily exclusionary if chronic inflammatory demyelinating polyneuropathy (CIDP) is confirmed as the main diagnosis, as determined by the investigator and confirmed by the adjudication committee Has known allergies, hypersensitivity, or intolerance to nipocalimab or its excipients Other protocol-defined exclusion criteria will apply

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nipocalimab<br>Participants in Stage A (Open-label) will receive a loading dose of nipocalimab (Dose 1) intravenous (IV) infusion on Day 1, followed by nipocalimab (Dose 2) IV infusion once every 2 weeks (q2w) from Week 2 to Week 12. Participants who demonstrate evidence of clinical improvement in Stage A (responders) will enter Stage B (Double-blind) and receive nipocalimab (Dose 2) IV infusion q2w starting on Day 1 up to Week 52. After completion of Stage B or discontinuation from Stage B due to relapse, participants will have the option to enter the open label extension (OLE) phase and receive nipocalimab (Dose 2) IV infusion q2w starting on OLE Day 1 until 2 years after marketing authorization in a participant's local country or until nipocalimab becomes available commercially or via other continued access program, whichever comes first. | Drug: Nipocalimab<br>* Nipocalimab will be administered intravenously.<br>* Other names: M281;|
| Placebo Comparator: Placebo<br>Participants receiving nipocalimab in Stage A and who demonstrate evidence of clinical improvement in Stage A (responders) will enter Stage B (Double-blind) and receive placebo IV infusion q2w starting on Day 1 up to Week 52. After completion of Stage B or discontinuation from Stage B due to relapse, participants will have the option to enter the open label extension (OLE) phase and receive nipocalimab (Dose 2) IV infusion q2w starting on OLE Day 1 until 2 years after marketing authorization in a participant's local country or until nipocalimab becomes available commercially or via other continued access program, whichever comes first. | Drug: Placebo<br>* Placebo will be administered intravenously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage B: Time to First Occurrence of a Relapse Event | Stage B time to first occurrence of a relapse event will be reported. | Up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage A: Time to Initial Confirmed Evidence of Clinical Improvement (ECI) | Time to initial confirmed ECI will be reported. | 12 weeks | 
| Stage A: Percentage of Responders as Determined by ECI | Stage A percentage of responders as determined by ECI will be reported. | 12 weeks | 
| Stage A: Change from Baseline Over Time in Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Scale Score | Change from Stage A baseline over time in adjusted INCAT disability scale score will be reported. The INCAT disability scale is a clinician-rated assessment that measures activity limitation and degree of functional disability. The INCAT scale is an ordinal scale scored from 0 to 10, with higher scores indicating more disability. | Baseline to 12 weeks | 
| Stage A: Change from Stage A Baseline Over Time in Medical Research Council (MRC) Muscle Grading Scale Sum Score | Change from Stage A baseline over time in MRC muscle grading scale sum score will be reported. The MRC muscle grading scale is a clinician-rated outcome that provides a strength rating (on a scale from 0 [no visible contraction] to 5 [normal]) in 6 muscles collected bilaterally: deltoid, biceps, wrist extensors, iliopsoas, quadriceps, tibialis anterior. Lower scores indicate greater impairment. | Baseline to 12 weeks | 
| Stage A: Change from Baseline Over Time in Inflammatory Rasch-Built Overall Disability Scale (I-RODS) Centile Score | Change from Stage A baseline over time in I-RODS centile score will be reported. The I-RODS comprises of 24 items representing common daily activities that address upper and lower limb disability and range in difficulty from very easy to very difficult. Lower scores indicate greater activity and social participation limitations. | Baseline to 12 weeks | 
| Stage A: Change from Baseline Over Time in Mean Grip Strength (Dominant Hand) | Change from Stage A baseline over time in mean grip strength (dominant hand) will be reported. Grip Strength is a quantifiable, objective performance outcome measure of hand strength, which can be measured using various devices (for example, Martin Vigorimeter and Jamar Dynamometer). | Baseline to 12 weeks | 
| Stage A: Change from Baseline Over Time in Mean Grip Strength (Non-Dominant Hand) | Change from Stage A baseline over time in mean grip strength (non-dominant hand) will be reported. Grip Strength is a quantifiable, objective performance outcome measure of hand strength, which can be measured using various devices (for example, Martin Vigorimeter and Jamar Dynamometer). | Baseline to 12 weeks | 
| Stage B: Time to First Adjusted INCAT Disability Scale Score Deterioration Relative to Baseline | Time to first adjusted INCAT disability scale score deterioration relative to Stage B baseline will be reported. | Up to 52 weeks | 
| Stage B: Time to First Switch to Intravenous Immunoglobulin (IVIg) or Other Standard of Care (SoC) as a Result of Investigator-assessed Lack of Efficacy as Confirmed by an Independent RAC Relative to Baseline | Time to first switch to IVIg or other SoC as a result of investigator-assessed lack of efficacy as confirmed by an independent Relapse Adjudication Committee (RAC) relative to Stage B baseline will be reported. | Up to 52 weeks | 
| Stage B: Change from Baseline Over Time in Adjusted INCAT Disability Score | Change from Stage B baseline over time in adjusted INCAT disability score will be reported. | Up to 52 weeks | 
| Stage B: Change from Baseline Over Time in MRC Muscle Grading Scale Sum Score | Change from Stage B baseline over time in MRC Muscle Grading Scale Sum score will be reported. | Up to 52 weeks | 
| Stage B: Change from Baseline Over Time in I-RODS Centile Score | Change from Stage B baseline over time in I-RODS centile score will be reported. | Up to 52 weeks | 
| Stage B: Change from Baseline Over Time in Mean Grip Strength (Dominant Hand) | Change from Stage B baseline over time in mean grip strength (dominant hand) will be reported. Grip Strength is a quantifiable, objective performance outcome measure of hand strength, which can be measured using various devices (for example, Martin Vigorimeter and Jamar Dynamometer). | Up to 52 weeks | 
| Stage B: Change from Baseline Over Time in Mean Grip Strength (Non-Dominant Hand) | Change from Stage B baseline over time in mean grip strength (non-dominant hand) will be reported. Grip Strength is a quantifiable, objective performance outcome measure of hand strength, which can be measured using various devices (for example, Martin Vigorimeter and Jamar Dynamometer). | Up to 52 weeks | 
| Stage B: Number of Participants with Binary Response Endpoint Satisfying all 4 Conditions: a) An Improved Adjusted INCAT Disability Score Compared to Baseline; b) Not Relapsing; c) Not Switching to SoC; d) Not Discontinuing Treatment | Number of participants with Binary response endpoint satisfying all 4 conditions: a) an improved adjusted INCAT Disability Score compared to Stage B baseline; b) not relapsing; c) not switching to SoC; d) not discontinuing treatment, will be reported. | Up to 52 weeks | 
| Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment | Stage A: 12 weeks; Stage B: Up to 52 weeks | 
| Percentage of Participants with Serious Adverse Events (SAEs) | SAE is an adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important. | Stage A: 12 weeks; Stage B: Up to 52 weeks | 
| Number of Participants with Change in Electrocardiogram (ECG) Values Over Time | Number of participants with change in ECG values over time will be reported. | Stage A: 12 weeks; Stage B: Up to 52 weeks | 
| Number of Participants with Change in Vital Signs Values Over Time | Number of participants with change in vital signs values over time will be reported. | Stage A: 12 weeks; Stage B: Up to 52 weeks | 
| Number of Participants with Change in Clinical Laboratory Values Over Time | Number of participants with change in clinical laboratory values over time will be reported. | Stage A: 12 weeks; Stage B: Up to 52 weeks | 
| Number of Participants with Clinically Significant ECG Abnormalities | Number of participants in clinically significant ECG abnormalities will be reported. | Stage A: 12 weeks; Stage B: Up to 52 weeks | 
| Number of Participants with Clinically Significant Vital Signs Abnormalities | Number of participants in clinically significant vital signs abnormalities will be reported. | Stage A: 12 weeks; Stage B: Up to 52 weeks | 
| Number of Participants with Clinically Significant Clinical Laboratory Abnormalities | Number of participants in clinically significant clinical laboratory abnormalities will be reported. | Stage A: 12 weeks; Stage B: Up to 52 weeks | 
| Percentage of Participants with Suicidal Ideation or Suicidal Behavior based on the Columbia-Suicide Severity Rating Scale (C-SSRS) | Percentage of participants with suicidal ideation or suicidal behavior based on the C-SSRS will be reported. | Stage A: 12 weeks; Stage B: Up to 52 weeks | 
| Serum Nipocalimab Concentrations Over Time in Participants Receiving Active Study Intervention | Serum nipocalimab concentrations over time in participants receiving active study intervention will be reported. | Stage A: 12 weeks; Stage B: Up to 52 weeks | 
| Number of Participants with Anti-drug Antibodies (ADA) to Nipocalimab | Number of participants with ADA to Nipocalimab will be reported. | Stage A: 12 weeks; Stage B: Up to 52 weeks | 
| Titers of ADA to Nipocalimab | Titers of ADA to nipocalimab will be reported. | Stage A: 12 weeks; Stage B: Up to 52 weeks | 
| Number of Participants with Neutralizing Antibodies (NAb) to Nipocalimab | Number of participants with NAb to Nipocalimab will be reported. | Stage A: 12 weeks; Stage B: Up to 52 weeks | 
| Change from Baseline in Total Serum Immunoglobulin (IgG) Concentrations Levels Over Time | Change from baseline in total serum IgG concentrations levels over time will be reported. | Stage A: Baseline to 12 weeks; Stage B: Baseline up to 52 weeks |