UMIN-CTR Clinical Trial

Basic information
Public 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
Acronym	RECIPE Trial
Scientific 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
Scientific Title:Acronym	RECIPE Trial
Region	Japan

Condition
Condition	Chronic Inflammatory Demyelinating Polyneuropathy
Classification by specialty	Neurology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To evaluate the efficacy and safety of rituximab (genetical recombination) intravenously administered to CIDP patients with positive or negative IgG4 autoantibody.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	Adjusted INCAT Disability Scale
Key secondary outcomes	1) Grip strength (left/right) 2) Rasch-built Overall Disability Scale (R-ODS) 3) Medical Research Council (MRC) Sum Score 4) Nerve conduction study (motor nerves: median, ulnar, tibial, and peroneal nerves) 5) Cerebrospinal fluid protein level 6) B cell counts (CD19 positive and CD20 positive cell counts) and T cell counts (CD3 positive, CD4 positive, and CD8 positive cell counts) 7) Expression of human anti-chimeric antibodies (HACA) 8) Serum rituximab (genetical recombination) level 9) Serum antibody titers of IgG4 (CNTN-1 and NF-155) and these IgG subclasses 10) Serum neurofilament 11) Adverse events 12) Vital signs, laboratory values

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Double blind -all involved are blinded
Control	Placebo
Stratification	YES
Dynamic allocation	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking	YES
Concealment

Intervention
No. of arms	3
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	CIDP patients with positive IgG4 autoantibody (CNTN-1 or NF-155): Administer 375 mg/m2 of rituximab (genetical recombination) IV infusion once weekly for 4 doses.
Interventions/Control_2	CIDP patients with positive IgG4 autoantibody (CNTN-1 or NF-155): Administer placebo IV infusion once weekly for 4 doses.
Interventions/Control_3	CIDP patients with negative IgG4 autoantibody (CNTN-1 and NF-155): Administer 375 mg/m2 of rituximab (genetical recombination) IV infusion once weekly for 4 doses.
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	12 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	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 meeting one of the following conditions: 1) Patients with positive serum IgG4 autoantibody (CNTN-1 or NF-155) confirmed by the time of enrollment in the study 2) 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 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 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
Key exclusion criteria	1. Patients with disease meeting one of the following exclusion criteria defined in the modified EFNS/PNS diagnostic criteria. 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 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 prior to the enrollment 8. Patients who have participated in another clinical study within 3 months prior to the enrollment or patients who are participating in another study 9. Patients with poorly controlled diabetes 10. Patients who have or are suspected to have active infection 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 HBV-DNA test is negative, 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 12. Patients with leukopenia, neutropenia, or lymphopenia 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 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
Target sample size	25

Research contact person
Name of lead principal investigator	1st name Masahiro Middle name Last name Iijima
Organization	Nagoya University Hospital
Division name	Department of Advanced Medicine
Zip code	466-8560
Address	65 Tsurumai-cho, Showa-ku, Nagoya, Aich
TEL	052-744-2389
Email	ijama@med.nagoya-u.ac.jp

Public contact
Name of contact person	1st name Shinobu Middle name Last name Shimizu
Organization	Nagoya University Hospital
Division name	Department of Advanced Medicine
Zip code	466-8560
Address	65 Tsurumai-cho, Showa-ku, Nagoya, Aich
TEL	052-744-2942
Homepage URL
Email	s-shimizu@med.nagoya-u.ac.jp

Sponsor
Institute	Nagoya University Hospital
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor	Zenyaku Kogyo Co., Ltd.
Name of secondary funder(s)	Zenyaku Kogyo Co., Ltd.

IRB Contact (For public release)
Organization	Nagoya University Hospital Institutional review board
Address	65 Tsurumai-cho, Showa-ku, Nagoya, Aich
Tel	052-744-1958
Email	center@med.nagoya-u.ac.jp

Secondary IDs
Secondary IDs	YES
Study ID_1	jRCT2041180037
Org. issuing International ID_1	Japan Registry of Clinical Trial
Study ID_2	NCT03864185
Org. issuing International ID_2	U.S. National Library of Medicine.
IND to MHLW

Institutions
Institutions	名古屋大学医学部附属病院（愛知県）、千葉大学医学部附属病院（千葉県）、山口大学医学部附属病院（山口県）、九州大学病院（福岡県）

Other administrative information
Date of disclosure of the study information	2019 Year 02 Month 02 Day

Related information
URL releasing protocol	https://www.researchprotocols.org/2020/4/e17117/
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled	27
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2018 Year 11 Month 28 Day
Date of IRB	2018 Year 12 Month 21 Day
Anticipated trial start date	2019 Year 03 Month 28 Day
Last follow-up date	2021 Year 06 Month 02 Day
Date of closure to data entry
Date trial data considered complete	2021 Year 09 Month 10 Day
Date analysis concluded	2022 Year 03 Month 28 Day

Other
Other related information

Management information
Registered date	2019 Year 02 Month 02 Day
Last modified on	2022 Year 05 Month 26 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000040728