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The Evaluation of Efficacy and Safety of Additional Rituximab (Genetical Recombination) in Refractory Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Patients with Immunoglobulin G4 (IgG4) Autoantibodies in the 2nd Exploratory Clinical Study in Patients Requested Medical Care (RECIPE-2 Study)

The Evaluation of Efficacy and Safety of Additional Rituximab (Genetical Recombination) in Refractory Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Patients with Immunoglobulin G4 (IgG4) Autoantibodies in the 2nd Exploratory Clinical Study in Patients Requested Medical Care (RECIPE-2 Study)

5

The gender ratio was 80% male (4/5 cases). The mean age of consent was 46.0 years. The mean height was 172.52 cm, and the mean weight was 74.46 kg. The mean duration of CIDP was 104.0 months. The proportion of typical CIDP was 80% (4/5 cases). There was one case of CIDP variants, which was distal dominant type (DADS). All patients were 'yes' for the presence or absence of drug therapy for previously treated CIDP. The proportion of patients with plasma purification therapy 'yes' for pre-treated CIDP was 60% (3/5). All patients were 'no' for behavioral therapy for pre-treated CIDP. Complications were present in 80% (4/5) of cases; NF-155 was positive in all. Serum pregnancy tests were performed on one female patient and confirmed negative. All dominant hands were right-handed.

Consent was obtained from five patients and all five were deemed eligible. There were no cases of pre-treatment drop-outs or treatment discontinuation and all five patients completed the treatment.

Adverse events (incidence and number of events) occurred in 80.0% (4/5 patients). Grade 3 adverse events and serious adverse events occurred in one patient. The adverse events occurring in two or more patients were injection-related reactions and headache syndrome. Adverse events not causally related to rituximab occurred in 60% (3/5 patients) and were injection-related reactions (4 patients). No adverse events leading to discontinuation of treatment were observed.

The proportion of patients who improved by more than one from baseline on the primary endpoint, the adjusted INCAT disability scale (FAS/PPS), was 80.0% [28.4%, 99.5%] (4 out of 5 patients) at 26, 38, and 52 weeks post-treatment compared with pre-treatment. The primary endpoint of change in the adjusted INCAT disability scale also showed improvement compared with baseline at 52 weeks, suggesting a benefit from rituximab treatment. The secondary endpoints of change in grip strength, R-ODS, MRC total score, nerve conduction studies, and CSF protein also showed improvement compared to baseline at 52 weeks, suggesting a benefit from rituximab treatment.

In terms of safety, one case of a fall-induced fracture, not causally related to rituximab, occurred. Other adverse events were non-serious, posing no issues for study continuation. Regarding efficacy, 80% of patients showed improvement in at least one adjusted INCAT disability scale from baseline, along with enhancements in grip strength, R-ODS, MRC sum score, nerve conduction studies, and CSF protein changes. These results imply rituximab's effectiveness in patients with IgG4 subclass autoantibodies.

Dec. 31, 2024

No

None.

https://jrct.mhlw.go.jp/latest-detail/jRCTs041210046

Katsuno Masahisa

Nagoya University School of Medicine

65 Tsurumai-cho, Showa-ku, Nagoya, Aichi

ka2no@med.nagoya-u.ac.jp

Fukami Yuki

Nagoya University School of Medicine

65 Tsurumai-cho, Showa-ku, Nagoya, Aichi

+81-52-744-2391

yuki.fukami@med.nagoya-u.ac.jp

Complete

Aug. 12, 2021

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Patients with definite CIDP diagnosed according to the modified diagnostic criteria of the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) (2010) by the time of enrollment in the study
2. Patients with positive serum IgG4 autoantibody (NF-155) confirmed by the time of enrollment in the study
3. Patients with refractory CIDP not responding adequately to treatment with corticosteroids 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 corticosteroids and IVIg
4. Patients with total adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Scale scores of 2 to 8 at enrollment
5. Patients meeting one of the following conditions:
1) Patients received rituximab (genetical recombination) IV infusion for CIDP treatment
2) Patients received rituximab (genetical recombination) or placebo IV infusion in RECIPE trial participant
6. Patients aged 20 years or older at informed consent
7. Patients who give their voluntary written consent after having received adequate information on this study

1. Patients with disease meeting one of the following exclusion criteria defined in the modified EFNS/PNS diagnostic criteria (2010).
1) Borrelia burgdorferi infection (Lyme disease), diphtheria, drug or toxin exposure probably to have caused the neuropathy Hereditary demyelinating neuropathy
2) Prominent sphincter disturbance
3) Diagnosis of multifocal motor neuropathy
4) IgM monoclonal gammopathy with high antibody titers to myelin-associated glycoprotein
5) Other causes for demyelinating neuropathy including POEMS syndrome, osteosclerotic myeloma, diabetic and non-diabetic lumbosacral radiculoplexus neuropathy
PNS lymphoma and amyloidosis may occasionally have demyelinating features
2. Patients who have started or have increased the dose of corticosteroids for CIDP within 12 weeks prior to the enrollment
3. Patients who have started or have increased the dose of IVIg within 8 weeks prior to the enrollment
4. Patients who have undergone 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)
5. 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
6. Patients who have undergone hematopoietic stem cell transplant prior to the enrollment
7. Patients who have used rituximab (genetical recombination) within 6 months prior to the enrollment
8. 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
9. Patients with poorly controlled diabetes
10. Patients who have or are suspected of having an active infection (infection requiring treatment with systemic antimicrobial, antifungal, or antiviral agents) at the time of the enrollment
11. Patients tested positive for HBs antigen, HBs antibody, HBc antibody, and/or HCV antibody (patients with positive hepatitis B surface antibody or core 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
12. Patients with leukopenia (less than 2,000 /mm3), neutropenia (less than 1,000 /mm3), or lymphopenia (less than 500 /mm3) at the time of the enrollment
13. Patients with a history of serious hypersensitivity or anaphylactic reaction to one of the ingredients in the investigational drug or murine protein-containing products
14. Patients with serious comorbidity (e.g., hepatic, renal, cardiac, lung, hematologic, or brain disease)
15. Female patients who are pregnant, lactating, or potentially pregnant, or patients who are not willing to use contraceptive measures during the study period
16. Patients who are judged to be unsuitable by the investigator or a sub-investigator

Both

Refractory Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

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

Chronicity, Demyelination, Peripheral Neuropathy

Rituximab

G618

D000069283

Adjusted INCAT Scale

1) Grasp power
2) R-ODS
3) MRC Sum Score
4) Nerve conduction study (motor nerves: median, ulnar, tibial, and peroneal nerves)
5) Cerebrospinal fluid protein level
6) Adverse events

+81-52-744-2479

July. 26, 2021

none