The Evaluation of Efficacy and Safety of Rituximab (Genetical Recombination) in Refractory Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Patients With Immunoglobulin G4 (IgG4) Autoantibodies in the Exploratory Clinical Trial

Nagoya University4 sites in 1 country25 target enrollmentMarch 28, 2019

ConditionsChronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
Sponsor: Nagoya University
Enrollment: 25
Locations: 4
Primary Endpoint: Rate of patients with improvement in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

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

Registry

clinicaltrials.gov

Start Date

March 28, 2019

End Date

May 27, 2021

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Nagoya University

Responsible Party

Principal Investigator

Masahiro Iijima

Designated Associate Professor

Nagoya University

Eligibility Criteria

Inclusion Criteria

•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)

Exclusion Criteria

•Patients with disease meeting one of the following exclusion criteria defined in the modified EFNS/PNS diagnostic criteria (2010).
•(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

Outcomes

Primary Outcomes

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

Time Frame: Up to 52 weeks

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.

Secondary Outcomes

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)
Cerebrospinal fluid protein level(Up to 52 weeks)
B cell counts (CD19 positive and CD20 positive cell counts) and T cell counts (CD3 positive, CD4 positive, and CD8 positive cell counts)(Up to 52 weeks)
Serum antibody titers of IgG4 (CNTN-1 and NF-155) and these IgG subclass(Up to 52 weeks)
Expression of HACA(Up to 52 weeks)
Maximum serum concentration (Cmax) of rituximab (genetical recombination)(Up to 52 weeks)
Half-life (t1/2) of rituximab (genetical recombination)(Up to 52 weeks)
Clearance (CL) of rituximab (genetical recombination)(Up to 52 weeks)
Mean residence time (MRT) of rituximab (genetical recombination)(Up to 52 weeks)
Volume of distribution (Vds) of rituximab (genetical recombination) level(Up to 52 weeks)
Serum neurofilament(Up to 52 weeks)
Change in grip strength (kPa)(Up to 52 weeks)
Change in motor nerve compound muscle action potential (CMAP)(Up to 52 weeks)
Change in motor nerve conduction velocity(Up to 52 weeks)
Serum rituximab (genetical recombination) level(Up to 52 weeks)
Area under the curve (AUC) of blood concentration of rituximab (genetical recombination)(Up to 52 weeks)