Rituximab in Chronic Inflammatory Demyelinating Polyneuropathy

NCT04480450 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: R4CIDP
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

CIDP is a heterogeneous disease with variable responses to therapy. Recently, a distinctive subgroup of patients with serum autoantibodies to the paranodal proteins contactin and neurofascin have been identified. Although they present with active and serious disease, multiple clinical reports suggest that these patients can be cured with a treatment that depletes B cells and presumably eliminates pathogenic autoantibodies. However, beyond that subgroup of CIDP patients, which CIDP patients might benefit from Rituximab and B cell depletion is unknown. This Phase II study will treat 3 homogenous groups of 16 CIDP patients each with Rituximab in order to determine if there are subgroups that can be taken off current medications and put into long-term remission. The results from this study will be used to design a future larger trial. Biomarkers including paranodal antibodies, serum neurofilament light chains, anti-ganglioside antibodies will be obtained in order to learn about disease pathogenesis and possibly target therapy

Conditions

Chronic Inflammatory Demyelinating Polyneuropathy

Keywords

CIDP

Outcome Measures

Primary Outcomes (1)

• Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score

  The INCAT disability scale captures upper and lower limb dysfunction separately on a scale of 0 to 5, which are then added together for a total composite score ranging between 0 and 10.15 Lower scores indicate no or minimal disability (no arm dysfunction or walking abnormality), and higher scores indicate more disability (no purposeful arm movement or restricted to wheelchair). The adjusted INCAT disability score is identical to the INCAT disability score with the exception that changes in upper limb function from 0 (normal) to 1 (minor symptoms) are excluded. This exclusion was made because upper limb changes from 0 to 1 (minor symptoms in the fingers which do not impair any functional activities) were not judged by regulatory agencies to be clinically significant in all patients. With the exception of a change in the upper limb score from 0 to 1, all other 1 point changes in the INCAT score are considered clinically significant.

  48 Weeks

Secondary Outcomes (6)

• Inflammatory-Rasch-built Overall Disability Scale (I-RODS)

  48 Weeks

• Modified Fatigue Severity Scale (mFSS)

  48 Weeks

• Visual Analog Pain Severity Scale (VAS)

  48 Weeks

• Martin vigorimeter grip strength

  48 Weeks

• Medical Research Council (MRC) Sum Score

  48 Weeks

Study Arms (2)

IVIg/SCIg < 3 Years Arm

ACTIVE COMPARATOR

Patients with CIDP successfully treated with IVIg/SCIg for under 12 months. Subjects will receive an intravenous infusion of 1,000mg Rituximab at Week 0 and Week 2.

Drug: Rituximab

IVIg/SCIg > 3 Years Arm

ACTIVE COMPARATOR

Patients with CIDP successfully treated with IVIg/SCIg for more than 12 months. Subjects will receive an intravenous infusion of 1,000mg Rituximab at Week 0 and Week 2.

Drug: Rituximab

Interventions

Rituximab DRUG

Rituximab is a highly purified, 1328-amino acid antibody with an approximate molecular mass of 145 kD. Rituximab is a mouse human chimeric monoclonal antibody against CD20. Administration leads to between 90 and 100% peripheral B cell depletion via complement dependent cytotoxicity.

IVIg/SCIg < 3 Years Arm; IVIg/SCIg > 3 Years Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained from subjects indicating that they understand the purpose of and procedures required for the study and are willing to participate
• Male or female, aged ≥18 years
• Documented diagnosis of typical CIDP according to the European Academy of Neurology/Peripheral Nerve Society criteria 202127
• Must be willing to complete the study and return for follow-up visits.
• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment.
• Successfully treated CIDP patients. Data at or prior to the screening visit must show evidence that during the course of therapy either the INCAT score improved by 1 or more points or improvement occurred according to the physician opinion.
• CIDP disease stability is based on 2 visits that are 3 or more months apart documented at or prior to the screening visit by assessing unchanged CIDP status per physician opinion. The subject must be at the same dosage and frequency of CIDP therapy in between these 2 timepoints.
• Belonging to 1 of the following 2 treatment groups:
• IVIg/SCIg for up to 3 years.
• IVIg/SCIg for more than 3 years.
• Off steroids for at least 3 months before screen visit. Topical steroids and infrequent intraarticular steroids are allowed.
• No anticipated change in dosage or CIDP therapy from week 0 to week 24.
• Off concurrent immunosuppressive agents (such as azathioprine, methotrexate, mycophenolate mofetil, or cyclosporine or cyclophosphamide or any other agent) for at least 6 months prior to screening visit.

You may not qualify if:

• Female subjects who are premenopausal and are
• pregnant on the basis of a serum pregnancy test,
• breast-feeding, or
• not using an effective method of double barrier (1 hormonal plus 1 barrier method or 2 simultaneous barrier methods) or birth control (birth control pills, male condom, female condom, intrauterine device, Norplant, tubal ligation, or other sterilization procedures).
• Participation in another clinical study within 30 days before entering the study or during the study
• Employee or direct relative of an employee of the study site or Sponsor
• Other medical condition, laboratory finding, or physical exam finding that precludes participation
• A neuropathy of other causes, including:
• A motor syndrome that fulfils criteria for multifocal motor neuropathy (MMN) with conduction block
• CIDP with monoclonal gammopathy of uncertain significance (CIDP-MGUS) or monoclonal gammopathy associated with an oncologic diagnosis
• Neuropathies secondary to infections, disorders, or systemic diseases
• Drug-, biologic-, chemotherapy-, or toxin-induced peripheral neuropathy
• Hereditary demyelinating neuropathies
• Central demyelinating disorders (e.g. multiple sclerosis)
• Others, like polyneuropathy, lumbosacral radiculoplexus neuropathy

Sponsors & Collaborators

• University of Kansas Medical Center: lead

MeSH Terms

Conditions

Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Polyradiculoneuropathy; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Mazen Dimachkie, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: July 21, 2020
• Study Start: July 1, 2025
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: September 17, 2025

Record last verified: 2025-09