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

Polyradiculoneuropathy, Chronic Inflammatory Demyelinating Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05327114
• Other study ID #: CR109195
• Secondary ID: 80202135CDP30012
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: September 23, 2022
• Est. completion date: September 30, 2028

Study information

• Verified date: April 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 201
• Est. completion date: September 30, 2028
• Est. primary completion date: May 14, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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

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

Related Conditions & MeSH terms

• Polyneuropathies
• Polyradiculoneuropathy
• Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Intervention

Drug:
• Nipocalimab
Nipocalimab will be administered intravenously.
• Placebo
Placebo will be administered intravenously.

Locations

Country	Name	City	State
China	Beijing Tiantan Hospital, Capital Medical University	Beijing
China	Peking University First Hospital	Beijing
China	Peking University Third Hospital	Beijing
China	Xuanwu Hospital ,Capital Medical University	Beijing
China	The First Hospital of Jilin University	Changchun
China	The Third Xiangya Hospital of Central Sourth University	Changsha
China	Xiangya Hospital Central South University	Changsha
China	Chifeng Municipal Hospital	Chifeng
China	Fujian Medical University Union Hospital	Fuzhou
China	The First Affiliated Hospital, Sun Yat-sen University	Guang Zhou
China	Qianfoshan hospital of Shandong Province	Jinan
China	The First Affiliated Hospital of NanChang University	Nanchang
China	Huashan Hospital Fudan University	Shanghai
China	Tong Ren Hospital Shanghai Jiao Tong University school of medicine	Shanghai
China	Xi 'an GaoXin Hospital	Xi'an
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Králové
Czechia	Fakultni nemocnice Ostrava	Ostrava
Czechia	Pardubicka krajska nemocnice a.s.	Pardubice
France	CHU Bordeaux	Bordeaux
France	Hospices Civils de Lyon HCL	Bron
France	Hopital de Bicetre	Le Kremlin Bicêtre
France	CHRU Strasbourg	Strasbourg
Greece	Patras University Hospital	Patras
Greece	'Papageorgiou' General Hospital of Thessaloniki	Thessaloniki
Japan	Asahikawa Medical Center	Asahikawa
Japan	Tokyo Medical and Dental University Hospital	Bunkyo-Ku
Japan	Chiba University Hospital	Chiba-shi
Japan	Seirei Hamamatsu General Hospital	Hamamatsu
Japan	Kobe City Medical Center General Hospital	Hyogo
Japan	Tokai University Hospital	Isehara
Japan	National Center of Neurology and Psychiatry	Kodaira-shi
Japan	Saitama Medical Center	Koshigaya
Japan	Kumamoto University Hospital	Kumamoto
Japan	Chubu Rosai Hospital	Nagoya
Japan	Nagoya University Hospital	Nagoya-shi
Japan	Kindai University Hospital	Osaka Sayama shi
Japan	National Hospital Organization Sendai Medical Center	Sendai-City
Japan	Dokkyo Medical University Hospital	Shimotsuga Gun
Japan	Tokyo Women's Medical University Hospital	Shinjuku-ku
Japan	Tenri Hospital	Tenri
Japan	Toyama University Hospital	Toyama-shi
Japan	Yamaguchi University Hospital	Ube
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Poland	Centrum Medyczne	Chorzów
Poland	Specjalistyczne Gabinety Lekarskie	Kraków
Spain	Hosp. Virgen Macarena	Sevilla
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Shin Kong Wu Ho Su Memorial Hospital	Taipei
United Kingdom	NHS Greater Glasgow and Clyde	Glasgow
United States	Austin Neuromuscular Center	Austin	Texas
United States	IMMUNOe Health and Research Centers	Centennial	Colorado
United States	The Neurological Institute, PA	Charlotte	North Carolina
United States	Cleveland Clinic Main Campus	Cleveland	Ohio
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Neurology Associates PA	Maitland	Florida
United States	Advocate Health - Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	The Neurological Institute of New York	New York	New York
United States	South Shore Neurologic Associates - Patchogue	Patchogue	New York
United States	Beaumont Hospital Royal Oak	Royal Oak	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  China,  Czechia,  France,  Greece,  Japan,  Korea, Republic of,  Poland,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Stage A: Time to Initial Confirmed Evidence of Clinical Improvement (ECI)	Time to initial confirmed ECI will be reported.	12 weeks
Secondary	Stage A: Percentage of Responders as Determined by ECI	Stage A percentage of responders as determined by ECI will be reported.	12 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Titers of ADA to Nipocalimab	Titers of ADA to nipocalimab will be reported.	Stage A: 12 weeks; Stage B: Up to 52 weeks
Secondary	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
Secondary	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