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Name:
UMIN ID:

Recruitment status Completed
Unique ID issued by UMIN UMIN000013453
Receipt No. R000015709
Scientific Title A multi-center, randomized, double-blind, placebo-controlled trial to determine the efficacy of rituximab against a relapse of neuromyelitis optica spectrum disorders with anti-aquaporin 4 antibody
Date of disclosure of the study information 2014/03/18
Last modified on 2020/08/20

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Basic information
Public title A multi-center, randomized, double-blind, placebo-controlled trial to determine the efficacy of rituximab against a relapse of neuromyelitis optica spectrum disorders with anti-aquaporin 4 antibody
Acronym RIN-1
Scientific Title A multi-center, randomized, double-blind, placebo-controlled trial to determine the efficacy of rituximab against a relapse of neuromyelitis optica spectrum disorders with anti-aquaporin 4 antibody
Scientific Title:Acronym RIN-1
Region
Japan

Condition
Condition Neuromyelitis optica
Classification by specialty
Neurology
Classification by malignancy Others
Genomic information NO

Objectives
Narrative objectives1 To elucidate the effectiveness of rituximab against relapses of neuromyelitis optica spectrum disorders with anti-aquaporin 4 antibody
Basic objectives2 Safety
Basic objectives -Others
Trial characteristics_1 Confirmatory
Trial characteristics_2
Developmental phase Phase II,III

Assessment
Primary outcomes Time to the first relapse from the allocation
Key secondary outcomes Changes in Expanded Disability Status Scale (EDSS) and Quantification of Optic nerve and Spinal cord Impairment (QOSI) from the baseline condition, and reduction rate of steroid

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 YES
Institution consideration Institution is not considered as adjustment factor.
Blocking NO
Concealment Central registration

Intervention
No. of arms 2
Purpose of intervention Treatment
Type of intervention
Medicine
Interventions/Control_1 Rituximab intravenous infusion
Interventions/Control_2 Placebo
Interventions/Control_3
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
16 years-old <=
Age-upper limit
80 years-old >=
Gender Male and Female
Key inclusion criteria 1) Patients who are seropositive for anti-aquaporin 4 antibody (including those who have previously been seropositive).
2) Patients with a history of either optic neuritis or myelitis.
3) Patients under treatment with oral steroids of dosage of more than 5 mg (within 10% change for at least 3 months before registration).
4) EDSS between 0 and 7.0.
5) Patients who are neurologically stable.
6) Age between 16 and 80 years.
7) Either male or female. Either in-patients or outpatients.
8) Including women of childbearing ages who are negative for a pregnancy test on Visit 1 and consent avoidance of the pregnancy during the trial.
9) Patients who give written informed consent. Patients under 20 years of age are required parental consent.
10) Patients who are able to follow the study protocol and schedule and who can report their symptoms.
Key exclusion criteria 1) Patients with hypersensitivity to mouse protein derivatives or those with a history of anaphylactic reaction to components of rituximab.
2) Patients infected with HBV, HCV, or HIV, and those having active infectious diseases.
3) Patients with severe chronic infection or a history of recurrent infections.
4) Patients who have used a live vaccine within 6 months.
5) Patients under treatment with oral corticosteroid drugs of dosage of higher than 30 mg per day in prednisolone conversion.
6) Patients with previous use of cladribine or a monoclonal antibody, such as natalizumab or rituximab.
7) Patients with a history of radiation treatment (whole body irradiation or lymphoid irradiation) or a stem cell transplant.
8) Patients under treatment with mitoxantrone or cyclophosphamide within 12 months.
9) Patients under treatment with immunomodulatory drugs (interferon beta, glatiramer acetate) or immunoglobulin therapy within 6 months.
10) Patients under treatment with oral immunosuppressive agents other than steroids (e.g., azathioprine, tacrolimus, cyclosporine, cyclophosphamide, methotrexate, or fingolimod) within 3 months.
11) Patients who have received plasma exchange or intravenous steroid pulse therapy within 3 months.
12) Patients with autoimmune diseases, such as Sjogren's syndrome or systemic lupus erythematosus, requiring treatment with immunosuppressants.
13) Patients who are pregnant or feeding a baby.
14) Patients who are participating in other clinical trials for NMO.
15) Patients diagnosed as having a cancer.
16) Patients who are considered unfit for the enrollment in the trial after an investigation.
Target sample size 40

Research contact person
Name of lead principal investigator
1st name Masayuki
Middle name
Last name Tahara
Organization NHO Utano National Hospital
Division name Clinical Research Center
Zip code 6168255
Address 8 Ondoyma-cho, Narutaki, Ukyo-ku, Kyoto
TEL +81-075-461-5121
Email tahara.masayuki.ne@mail.hosp.go.jp

Public contact
Name of contact person
1st name Masayuki
Middle name
Last name Tahara
Organization NHO Utano National Hospital
Division name Clinical Research Center
Zip code 6168255
Address 8 Ondoyma-cho, Narutaki, Ukyo-ku, Kyoto
TEL +81-075-461-5121
Homepage URL http://www.nmo-utano.com
Email tahara.masayuki.ne@mail.hosp.go.jp

Sponsor
Institute Clinical Research Center, NHO Utano National Hospital
Institute
Department

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

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

IRB Contact (For public release)
Organization Institutional Review Board, National Hospital Organization Utano National Hospital
Address 8 Ondoyma-cho, Narutaki, Ukyo-ku, Kyoto
Tel +81-075-461-5121
Email ktiken@unh.hosp.go.jp

Secondary IDs
Secondary IDs NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions 国立病院機構宇多野病院(京都)、東北大学病院(宮城)、東京女子医科大学病院(東京)、産業医科大学付属病院(福岡)、広島大学病院(広島)、埼玉医科大学総合医療センター(埼玉)、奈良県立医科大学(奈良)、千葉大学(千葉)
Utano National Hospital (Kyoto), Tohoku University Hospital (Miyagi), Tokyo Women's Medical University Hospital (Tokyo), University of occupational and environmental Health (Fukuoka), Hiroshima University Hospital (Hiroshima), Saitama Medical Center (Saitama), Nara Medical University (Nara), Chiba University (Chiba)

Other administrative information
Date of disclosure of the study information
2014 Year 03 Month 18 Day

Related information
URL releasing protocol http://utanohosp.jp/html/medical/clinical/info_disclosure.html
Publication of results Published

Result
URL related to results and publications https://www.thelancet.com/journals/laneur/issue/vol19no4/PIIS1474-4422(20)X0004-4
Number of participants that the trial has enrolled 42
Results
Between May 10, 2014, and Aug 15, 2017, 38 participants were recruited and randomly allocated either rituximab (n=19) or placebo (n=19). Three (16%) patients assigned rituximab discontinued the study and were analysed as censored cases. Seven (37%) relapses occurred in patients allocated placebo and none were recorded in patients assigned rituximab (group difference 36.8%, 95% CI 12.3-65.5; log-rank p=0.0058).
Results date posted
2020 Year 08 Month 20 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
2020 Year 03 Month 19 Day
Baseline Characteristics
Patients aged 16-80 years with NMOSD who were seropositive for aquaporin 4 (AQP4) antibody, were taking 5-30 mg/day oral steroids, and had an Expanded Disability Status Scale (EDSS) score of 7.0 or less were eligible for the study. Individuals taking any other immunosuppressants were excluded.
Participant flow
Participants were randomly allocated (1:1) either rituximab or placebo by a computer-aided dynamic random allocation system. The doses of concomitant steroid (converted to equivalent doses of prednisolone) and relapses in previous 2 years were set as stratification factors. Participants and those assessing outcomes were unaware of group assignments.
Adverse events
Eight serious adverse events were recorded, four events in three (16%) patients assigned rituximab (lumbar compression fracture and infection around nail of right foot [n=1], diplopia [n=1], and uterine cancer [n=1]) and four events in two (11%) people allocated to placebo (exacerbation of glaucoma and bleeding in the right eye chamber after surgery [n=1], and visual impairment and asymptomatic white matter brain lesion on MRI [n=1]); all patients recovered. No deaths were reported.
Outcome measures
The primary outcome was time to first relapse within 72 weeks. Relapses were defined as patient-reported symptoms or any new signs consistent with CNS lesions and attributable objective changes in MRI or visual evoked potential.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status Completed
Date of protocol fixation
2014 Year 02 Month 28 Day
Date of IRB
2014 Year 04 Month 18 Day
Anticipated trial start date
2014 Year 05 Month 10 Day
Last follow-up date
2019 Year 01 Month 17 Day
Date of closure to data entry
2019 Year 06 Month 14 Day
Date trial data considered complete
2019 Year 06 Month 14 Day
Date analysis concluded

Other
Other related information

Management information
Registered date
2014 Year 03 Month 18 Day
Last modified on
2020 Year 08 Month 20 Day


Link to view the page
URL(English) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000015709

Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name


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