Brief Title
The Evaluation of Efficacy and Safety of Rituximab in Refractory CIDP Patients With IgG4 Autoantibodies
Official Title
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
Brief Summary
To evaluate the efficacy and safety of rituximab (genetical recombination) intravenously
administered to CIDP patients with positive or negative IgG4 autoantibody.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Rate of patients with improvement in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale
Secondary Outcome
Change in grip strength (kPa)
Condition
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
Intervention
Rituximab (genetical recombination)
Study Arms / Comparison Groups
Rituximab group (IgG4 autoantibody positive)
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
25
Start Date
March 28, 2019
Completion Date
May 27, 2021
Primary Completion Date
May 27, 2021
Eligibility Criteria
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 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
2. Patients who have started or have increased the dose of corticosteroid 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 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)
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 underwent hematopoietic stem cell transplant prior to the enrollment
7. Patients who have used rituximab (genetical recombination) 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 (HbA1c of 7 % or higher)
10. 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
11. 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
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 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
Gender
All
Ages
12 Years - N/A
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Masahiro Iijima, Ph. D, ,
Location Countries
Japan
Location Countries
Japan
Administrative Informations
NCT ID
NCT03864185
Organization ID
CAMCR-011
Secondary IDs
jRCT2041180037
Responsible Party
Principal Investigator
Study Sponsor
Nagoya University
Collaborators
Japan Agency for Medical Research and Development
Study Sponsor
Masahiro Iijima, Ph. D, Principal Investigator, Nagoya University Hospital
Verification Date
August 2021