The Evaluation of Efficacy and Safety of Rituximab in Refractory CIDP Patients With IgG4 Autoantibodies

NCT03864185 | Completed Phase 2

• 3 other identifiers: CAMCR-011jRCT2041180037UMIN000035753
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 4

Brief Summary

To evaluate the efficacy and safety of rituximab (genetical recombination) intravenously administered to CIDP patients with positive or negative IgG4 autoantibody.

Conditions

Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

Keywords

IgG4 autoantibody; Neurofascin-155; Contactin-1; Rituximab

Outcome Measures

Primary Outcomes (1)

• Rate of patients with improvement in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale

  Primary analysis will compare scores of adjusted INCAT Disability Scale evaluated prior to treatment (at the time of enrollment) and scores at each timepoint after week 26 to calculate the proportion of patients who achieve an improvement of one and more from the baseline. The INCAT Disability Scale is an index to evaluate disorders in lower (gait) and upper (elevation of the upper arms and fine movement of the fingertips) extremities. The INCAT score is a 10-point scale and ranges from 0 (normal) to 10 (worst). For the "adjusted" INCAT score, a change in upper extremity score from 0 to 1 or 1 to 0 will not be considered meaningful in this evaluation.

  Up to 52 weeks

Secondary Outcomes (19)

• Change in grip strength (kPa)

  Up to 52 weeks

• Change in Rasch-built Overall Disability Scale (R-ODS) score

  Up to 52 weeks

• Change in Medical Research Council (MRC) Sum Score

  Up to 52 weeks

• Change in motor nerve distal latency

  Up to 52 weeks

• Change in motor nerve proximal latency

  Up to 52 weeks

Study Arms (3)

Rituximab group (IgG4 autoantibody positive)

ACTIVE COMPARATOR

Biological: Rituximab (genetical recombination)

Placebo group (IgG4 autoantibody positive)

PLACEBO COMPARATOR

Other: Placebo

Rituximab group (IgG4 autoantibody negative)

ACTIVE COMPARATOR

Biological: Rituximab (genetical recombination)

Interventions

Rituximab (genetical recombination) BIOLOGICAL

Administer 375 mg/m2 of rituximab (genetical recombination) IV infusion once weekly for 4 doses.

Rituximab group (IgG4 autoantibody negative); Rituximab group (IgG4 autoantibody positive)

Placebo OTHER

Administer placebo IV infusion once weekly for 4 doses.

Placebo group (IgG4 autoantibody positive)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with definite CIDP diagnosed according to the modified diagnostic criteria of European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) (2010) by the time of enrollment in the study
• Patients meeting one of the following conditions:
• (i) Patients with positive serum IgG4 autoantibody (CNTN-1 or NF-155) confirmed by the time of enrollment in the study
• (ii) Patients with negative serum IgG4 autoantibody (CNTN-1 and NF-155) confirmed by the time of enrollment in the study
• Patients with refractory CIDP not responding adequately to treatment with corticosteroid for 12 weeks, and intravenous immunoglobulin therapy (IVIg) for 8 weeks by the time of enrollment in the study, or those who are unable to administer or continue corticosteroid and IVIg
• Patients with total adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Scale scores of 2 to 8 at both preliminary enrollment and enrollment, and with the total score at enrollment equal to or worse than that at preliminary enrollment
• Patients aged 12 years or older at informed consent
• Patients who give their voluntary written consent after having received adequate information on this study (legally acceptable representatives should also give consent for underage patients, and informed assent should be obtained from children aged 12 to 15)

You may not qualify if:

• (i) Borrelia burgdorferi infection (Lyme disease), diphtheria, drug or toxin exposure probably to have caused the neuropathy Hereditary demyelinating neuropathy
• (ii) Prominent sphincter disturbance
• (iii) Diagnosis of multifocal motor neuropathy
• (iv) IgM monoclonal gammopathy with high titre antibodies to myelin-associated glycoprotein
• (v) Other causes for a demyelinating neuropathy including POEMS syndrome, osteosclerotic myeloma, diabetic and non-diabetic lumbosacral radiculoplexus neuropathy PNS lymphoma and amyloidosis may occasionally have demyelinating features
• Patients who have started or have increased the dose of corticosteroid for CIDP within 12 weeks prior to the enrollment
• Patients who have started or have increased the dose of IVIg within 8 weeks prior to the enrollment
• Patients who have underwent plasmapheresis within 8 weeks prior to the enrollment or patients with refractory disease not responding adequately to 8 weeks of plasmapheresis (plasma exchange or double-filtration plasmapheresis)
• Patients who have started or have increased the dose of an immunosuppressant (azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil, interferon alpha, interferon beta, etanercept, methotrexate, mitoxantrone, alemtuzumab, cladribine, tacrolimus, fingolimod) within 12 weeks prior to the enrollment
• Patients who have underwent hematopoietic stem cell transplant prior to the enrollment
• Patients who have used rituximab (genetical recombination) prior to the enrollment
• Patients who have participated in another clinical study within 3 months prior to the enrollment (enrollment is allowed for those participating in a clinical study in the range of Indications or Dosage and Administration in Japan) or patients who are participating in another study
• Patients with poorly controlled diabetes (HbA1c of 7 % or higher)
• Patients who have or are suspected to have active infection (infection requiring treatment with systemic antimicrobial, antifungal, or antiviral agents) at the time of the enrollment
• Patients tested positive for HBs antigen, HBs antibody, HBc antibody, and/or HCV antibody (patients with positive HBs antibody or HBc antibody can be enrolled when a hepatitis B virus-DNA test is negative \[below the limit of detection\], and hepatitis B virus-DNA and aspartate/alanine transaminase levels are monitored at fixed intervals), or patients with positive HIV antibody or HTLV-1 antibody at the time of the enrollment

Sponsors & Collaborators

• Nagoya University: lead
• Japan Agency for Medical Research and Development: collaborator
• Zenyaku Kogyo Co., Ltd.: collaborator

Study Sites (4)

Nagoya University Hospital

Nagoya, Aich, 466-8560, Japan

Location

Chiba University Hospital

Chiba, Japan

Location

Kyushu University Hospital

Fukuoka, Japan

Location

Yamaguchi University Hospital

Ube, Japan

Location

Related Publications (1)

• Shimizu S, Iijima M, Fukami Y, Tamura N, Nakatochi M, Ando M, Nishi R, Koike H, Kaida K, Koga M, Kanda T, Ogata H, Kira JI, Mori M, Kuwabara S, Katsuno M. Efficacy and Safety of Rituximab in Refractory CIDP With or Without IgG4 Autoantibodies (RECIPE): Protocol for a Double-Blind, Randomized, Placebo-Controlled Clinical Trial. JMIR Res Protoc. 2020 Apr 1;9(4):e17117. doi: 10.2196/17117.

  PMID: 32234705 BACKGROUND

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

• Masahiro Iijima, Ph. D

  Nagoya University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Designated Associate Professor

Study Record Dates

• First Submitted: February 19, 2019
• First Posted: March 6, 2019
• Study Start: March 28, 2019
• Primary Completion: May 27, 2021
• Study Completion: May 27, 2021
• Last Updated: August 20, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

JP (4)