UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000013453 |
|---|---|
| Receipt number | 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 23:57:46 |
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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
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
tahara.masayuki.ne@mail.hosp.go.jp
Sponsor or person
Institute
Clinical Research Center, NHO Utano National Hospital
Institute
Department
Personal name
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
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
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000015709
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