Efficacy and Safety Study of Nipocalimab for Adults With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
- Conditions
- Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
- Interventions
- Drug: Placebo
- Registration Number
- NCT05327114
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 201
- 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
- Inflammatory Neuropathy Cause and Treatment (INCAT) disability score between 2 and 9 at the Run-In Baseline visit for participants entering Run-In, or Stage A Baseline visit for participants directly entering Stage A. Participants with an INCAT score of 2 at trial entry must have this score exclusively from the leg disability score
- Fulfilling any of the following treatment conditions: a) Currently treated with oral corticosteroids (CS) less than or equal to (<=) 20 milligrams (mg)/day; or b) Currently treated with pulsed CS, and/or intravenous immunoglobulin (IVIg) or subcutaneous immunoglobulin (SCIg) and the participant is willing to discontinue no later than the run-in baseline visit; or c) Currently treated with oral CS greater than (>) 20 mg/day and the participant is willing to taper to <=20 mg/day during the run-in period; or d) Without previous treatment (treatment naive); or treatment with CS 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Nipocalimab Nipocalimab 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. Placebo Placebo 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.
- Primary Outcome Measures
Name Time Method Stage B: Time to First Occurrence of a Relapse Event Up to 52 weeks Stage B time to first occurrence of a relapse event will be reported.
- Secondary Outcome Measures
Name Time Method Stage A: Time to Initial Confirmed Evidence of Clinical Improvement (ECI) 12 weeks Time to initial confirmed ECI will be reported.
Stage A: Percentage of Responders as Determined by ECI 12 weeks Stage A percentage of responders as determined by ECI will be reported.
Stage A: Change from Baseline Over Time in Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Scale Score Baseline to 12 weeks 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.
Stage A: Change from Stage A Baseline Over Time in Medical Research Council (MRC) Muscle Grading Scale Sum Score Baseline to 12 weeks 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.
Stage B: Time to First Adjusted INCAT Disability Scale Score Deterioration Relative to Baseline Up to 52 weeks Time to first adjusted INCAT disability scale score deterioration relative to Stage B baseline will be reported.
Stage B: Change from Baseline Over Time in Mean Grip Strength (Dominant Hand) Up to 52 weeks 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).
Stage B: Change from Baseline Over Time in Mean Grip Strength (Non-Dominant Hand) Up to 52 weeks 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).
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 Up to 52 weeks 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.
Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) Stage A: 12 weeks; Stage B: Up to 52 weeks 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
Number of Participants with Change in Electrocardiogram (ECG) Values Over Time Stage A: 12 weeks; Stage B: Up to 52 weeks Number of participants with change in ECG values over time will be reported.
Number of Participants with Clinically Significant Clinical Laboratory Abnormalities Stage A: 12 weeks; Stage B: Up to 52 weeks Number of participants with clinically significant clinical laboratory abnormalities will be reported.
Percentage of Participants with Suicidal Ideation or Suicidal Behavior based on the Columbia-Suicide Severity Rating Scale (C-SSRS) Stage A: 12 weeks; Stage B: Up to 52 weeks Percentage of participants with suicidal ideation or suicidal behavior based on the C-SSRS will be reported.
Number of Participants with Anti-drug Antibodies (ADA) to Nipocalimab Stage A: 12 weeks; Stage B: Up to 52 weeks Number of participants with ADA to Nipocalimab will be reported.
Titers of ADA to Nipocalimab Stage A: 12 weeks; Stage B: Up to 52 weeks Titers of ADA to nipocalimab will be reported.
Stage A: Change from Baseline Over Time in Inflammatory Rasch-Built Overall Disability Scale (I-RODS) Centile Score Baseline to 12 weeks 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.
Stage A: Change from Baseline Over Time in Mean Grip Strength (Dominant Hand) Baseline to 12 weeks 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).
Stage A: Change from Baseline Over Time in Mean Grip Strength (Non-Dominant Hand) Baseline to 12 weeks 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).
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 Up to 52 weeks 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.
Stage B: Change from Baseline Over Time in Adjusted INCAT Disability Score Up to 52 weeks Change from Stage B baseline over time in adjusted INCAT disability score will be reported.
Stage B: Change from Baseline Over Time in MRC Muscle Grading Scale Sum Score Up to 52 weeks Change from Stage B baseline over time in MRC Muscle Grading Scale Sum score will be reported.
Stage B: Change from Baseline Over Time in I-RODS Centile Score Up to 52 weeks Change from Stage B baseline over time in I-RODS centile score will be reported.
Percentage of Participants with Serious Adverse Events (SAEs) Stage A: 12 weeks; Stage B: Up to 52 weeks 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.
Number of Participants with Change in Vital Signs Values Over Time Stage A: 12 weeks; Stage B: Up to 52 weeks Number of participants with change in vital signs values over time will be reported.
Number of Participants with Clinically Significant ECG Abnormalities Stage A: 12 weeks; Stage B: Up to 52 weeks Number of participants with clinically significant ECG abnormalities will be reported.
Number of Participants with Change in Clinical Laboratory Values Over Time Stage A: 12 weeks; Stage B: Up to 52 weeks Number of participants with change in clinical laboratory values over time will be reported.
Number of Participants with Clinically Significant Vital Signs Abnormalities Stage A: 12 weeks; Stage B: Up to 52 weeks Number of participants with clinically significant vital signs abnormalities will be reported.
Serum Nipocalimab Concentrations Over Time in Participants Receiving Active Study Intervention Stage A: 12 weeks; Stage B: Up to 52 weeks Serum nipocalimab concentrations over time in participants receiving active study intervention will be reported.
Number of Participants with Neutralizing Antibodies (NAb) to Nipocalimab Stage A: 12 weeks; Stage B: Up to 52 weeks Number of participants with NAb to Nipocalimab will be reported.
Change from Baseline in Total Serum Immunoglobulin (IgG) Concentrations Levels Over Time Stage A: Baseline to 12 weeks; Stage B: Baseline up to 52 weeks Change from baseline in total serum IgG concentrations levels over time will be reported.
Trial Locations
- Locations (92)
IRCCS Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Hosp. Univ. Donostia
🇪🇸Donostia, Spain
IMMUNOe Health and Research Centers
🇺🇸Centennial, Colorado, United States
Neurology Associates PA
🇺🇸Maitland, Florida, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Boston Clinical Trials
🇺🇸Boston, Massachusetts, United States
Beaumont Hospital Royal Oak
🇺🇸Royal Oak, Michigan, United States
The Neurological Institute of New York
🇺🇸New York, New York, United States
South Shore Neurologic Associates - Patchogue
🇺🇸Patchogue, New York, United States
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