Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
Conditions
Keywords
IgG4 autoantibody, Neurofascin-155, Contactin-1, Rituximab
Brief summary
To evaluate the efficacy and safety of rituximab (genetical recombination) intravenously administered to CIDP patients with positive or negative IgG4 autoantibody.
Interventions
BIOLOGICALRituximab (genetical recombination)
Administer 375 mg/m2 of rituximab (genetical recombination) IV infusion once weekly for 4 doses.
OTHERPlacebo
Administer placebo IV infusion once weekly for 4 doses.
Sponsors
Japan Agency for Medical Research and Development
Zenyaku Kogyo Co., Ltd.
Nagoya University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. 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 2. 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 3. 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 4. 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 5. Patients aged 12 years or older at informed consent 6. 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
1. Patients with disease meeting one of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of patients with improvement in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Rasch-built Overall Disability Scale (R-ODS) score | Up to 52 weeks | The differences of R-ODS score between prior to treatment and at each timepoint are summarized. R-ODS is consist of a 24-item questionnaire about daily living task with 3 response options: (0) impossible to perform, (1) performed with difficulty, and (2) easily performed. The R-ODS score is a 48-point scale (range: 0-48), and is converted into a centile metric score with values ranging from 0 (most severe activity and social participation limitations) to 100 (no activity and social participation limitations). |
| Change in Medical Research Council (MRC) Sum Score | Up to 52 weeks | The differences of MRC Sum Score between prior to treatment and at each timepoint are summarized. The MRC Sum Score is a scale to assess for 8 muscle groups (right and left side) as follow: Shoulder abduction, Elbow flexion, Wrist extension, Index finger abduction, Hip flexion, Knee extension, Foot dorsiflexion, Great toe dorsiflexion.The MRC Sum Score is a 80-point scale and ranges from 0 (paralysis) to 80 (normal strength). |
| Change in motor nerve distal latency | Up to 52 weeks | The differences of distal latency between prior to treatment and at each timepoint are summarized. |
| Change in motor nerve proximal latency | Up to 52 weeks | The differences of proximal latency between prior to treatment and at each timepoint are summarized. |
| Change in motor nerve compound muscle action potential (CMAP) | Up to 52 weeks | The differences of CMAP between prior to treatment and at each timepoint are summarized. |
| Change in motor nerve conduction velocity | Up to 52 weeks | The differences of motor nerve conduction velocity between prior to treatment and at each timepoint are summarized. |
| Cerebrospinal fluid protein level | Up to 52 weeks | Cerebrospinal fluid protein level at each timepoint are summarized. |
| 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 | B cell counts (CD19 positive and CD20 positive cell counts) and T cell counts (CD3 positive, CD4 positive, and CD8 positive cell counts) at each timepoint are summarized. |
| Expression of HACA | Up to 52 weeks | The number of patients expressing HACA, and the proportion and its 95% confidence interval of these patients at each timepoint are summarized. |
| Change in grip strength (kPa) | Up to 52 weeks | The differences of Grip strength (kPa) between prior to treatment and at each timepoint are summarized. |
| Maximum serum concentration (Cmax) of rituximab (genetical recombination) | Up to 52 weeks | Cmax of rituximab (genetical recombination) is summarized. |
| Area under the curve (AUC) of blood concentration of rituximab (genetical recombination) | Up to 52 weeks | AUC of blood concentration of rituximab (genetical recombination) is summarized. |
| Half-life (t1/2) of rituximab (genetical recombination) | Up to 52 weeks | t1/2 of rituximab (genetical recombination) is summarized. |
| Clearance (CL) of rituximab (genetical recombination) | Up to 52 weeks | CL of rituximab (genetical recombination) is summarized. |
| Mean residence time (MRT) of rituximab (genetical recombination) | Up to 52 weeks | MRT of rituximab (genetical recombination) is summarized. |
| Volume of distribution (Vds) of rituximab (genetical recombination) level | Up to 52 weeks | Vds of rituximab (genetical recombination) is summarized. |
| Serum antibody titers of IgG4 (CNTN-1 and NF-155) and these IgG subclass | Up to 52 weeks | Serum titers (CNTN-1 and NF-155, and these IgG subclasses 1 to 4) at each timepoint are summarized. |
| Serum neurofilament | Up to 52 weeks | Serum neurofilament level at each timepoint is summarized. |
| Serum rituximab (genetical recombination) level | Up to 52 weeks | Serum rituximab (genetical recombination) level at each timepoint are summarized. |
Countries
Japan
Outcome results
None listed