UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000031771 |
|---|---|
| Receipt number | R000036134 |
| Scientific Title | A Randomized, Double-Blind, Placebo-Controlled, Multicenter study to Evaluate Efficacy and Safety of MSA-01 in Patients with Multiple system atrophy. |
| Date of disclosure of the study information | 2018/03/16 |
| Last modified on | 2023/04/28 08:08:37 |
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Basic information
Public title
A Randomized, Double-Blind, Placebo-Controlled, Multicenter study to Evaluate Efficacy and Safety of MSA-01 in Patients with Multiple system atrophy.
Acronym
A Randomized, Double-Blind, Placebo-Controlled, Multicenter study to Evaluate Efficacy and Safety of MSA-01 in Patients with Multiple system atrophy.
Scientific Title
A Randomized, Double-Blind, Placebo-Controlled, Multicenter study to Evaluate Efficacy and Safety of MSA-01 in Patients with Multiple system atrophy.
Scientific Title:Acronym
A Randomized, Double-Blind, Placebo-Controlled, Multicenter study to Evaluate Efficacy and Safety of MSA-01 in Patients with Multiple system atrophy.
Region
| Japan |
Condition
Condition
Multiple system atrophy
Classification by specialty
| Neurology |
Classification by malignancy
Others
Genomic information
NO
Objectives
Narrative objectives1
To assess the efficacy and the safety of high-dose MSA-01 supplementation in patients with multiple system atrophy under the randomized, double-blind, placebo-controlled study.
Basic objectives2
Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Exploratory
Trial characteristics_2
Developmental phase
Phase II
Assessment
Primary outcomes
1)48-weeks progression rate for UMSARS part2
2)Safety (adverse events, vital signs, clinical examination and 12-lead ECG)
Key secondary outcomes
1)48-weeks progression rate for UMSARS part2
2)48-weeks progression rate for Barthal index score
3)48-weeks progression rate for SARA score
4)48-weeks progression rate for 10m walking time
5)Progression rate between MSA-C and MSA-P for the primary outcome or the secondary outcome
6)Progression rate between patients with and without COQ2 mutation for the primary outcome or the secondary outcome
7)Coenzyme Q10 levels in plasma
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
Central registration
Intervention
No. of arms
2
Purpose of intervention
Treatment
Type of intervention
| Medicine |
Interventions/Control_1
One daily MSA-01 for 48weeks with 300mg dose-escalation tolerable from 300mg up to 1500mg every 2 weeks.
Interventions/Control_2
One daily placebo for 48 weeks.
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
| 30 | years-old | <= |
Age-upper limit
| 80 | years-old | > |
Gender
Male and Female
Key inclusion criteria
[Observation period]
1.Subjects who were diagnosed as probable or possible multiple system atrophy on the basis of the Gilman criteria
2.Subjects who can walk 10 m independently with or without an assistive device including cane, walker, or handrails
3.Subjects who underwent through genetic testing for the detection of mutations in the COQ2 gene
4.Male or female subjects between the ages of 30 and 80 at time of informed consent
5.Subjects who can get an informed consent from themselves
6.Subjects who can be admitted or hospitalized at the medical institution participating in this study
The additional features include:
<Possible MSA-P or MSA-C>
Babinski sign with hyperreflexia
Stridor
<Possible MSA-P>
Rapidly progressive parkinsonism
Poor response to levodopa
Postural instability within 3 y of motor onset
Gait ataxia, cerebellar dysarthria, limb ataxia, or cerebellar oculomotor dysfunction
Dysphagia within 5 y of motor onset
Atrophy on MRI of putamen, middle cerebellar peduncle, pons, or cerebellum
Hypometabolism on FDG-PET in putamen, brainstem, or cerebellum
<Possible MSA-C>
Parkinsonism (bradykinesia and rigidity)
Atrophy on MRI of putamen, middle cerebellar peduncle, or pons
Hypometabolism on FDG-PET in putamen
Presynaptic nigrostriatal dopaminergic denervation on SPECT or PET
[At the beginning of dose-escalation period]
1. The change in total score of unified multiple system atrophy rating scale (UMSARS) part 2 were less than 3 during the observation period
2. Subjects who have not taken the prohibited concomitant medications (see 9.4)
3. No potential clinical risks has been found during the observation period
4. Subjects who are considered adequate to participate in the study by the investigator
Key exclusion criteria
1.Subjects who take medicines, quasi-drugs or supplement contain at least either one of ubiquinone, ubiquinol, idebenone (related products which are prohibited concomitantly), and statins at beginning of the observation period
2.Subjects with severe liver dysfunction (Child-Pugh class B-C)
3.Female subjects who are pregnant, nursing, or possibly pregnant during the trial period (females of childbearing potential are confirmed by either post-menopausal for 3 years prior to the time of informed consent or surgically sterile)
4.Subjects who have received any investigational drug within 3 months prior to informed consent
5.Subjects who are considered inadequate to participate in the study by the investigator
Target sample size
120
Research contact person
Name of lead principal investigator
| 1st name | |
| Middle name | |
| Last name | Shoji Tsuji, M.D., Ph.D. |
Organization
The University of Tokyo Hospital
Division name
Department of Neurology
Zip code
Address
7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
TEL
03-3815-5411
tsuji@m.u-tokyo.ac.jp
Public contact
Name of contact person
| 1st name | |
| Middle name | |
| Last name | Jun Mitsui, M.D., Ph.D. |
Organization
The University of Tokyo Hospital
Division name
Department of Neurology
Zip code
Address
7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
TEL
03-3815-5411
Homepage URL
mituij-tky@umin.ac.jp
Sponsor or person
Institute
The University of Tokyo Hospital
Institute
Department
Personal name
Funding Source
Organization
Japan Agency of Medical Research and Development
Organization
Division
Category of Funding Organization
Japanese Governmental office
Nationality of Funding Organization
Other related organizations
Co-sponsor
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Address
Tel
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
国立大学法人北海道大学病院(北海道)
新潟大学医歯学総合病院（新潟県）
独立行政法人国立病院機構東埼玉病院（埼玉県）
国立研究開発法人国立精神・神経医療研究センター（東京都）
千葉大学医学部附属病院（千葉県）
国立大学法人東京医科歯科大学医学部附属病院（東京都）
名古屋大学医学部附属病院（愛知県）
京都大学医学部附属病院（京都府）
鳥取大学医学部附属病院（鳥取県）
岡山大学病院（岡山県）
九州大学病院（福岡県）
鹿児島大学病院（鹿児島県）
Other administrative information
Date of disclosure of the study information
| 2018 | Year | 03 | Month | 16 | Day |
Related information
URL releasing protocol
https://www.thelancet.com/cms/10.1016/j.eclinm.2023.101920/attachment/db8b9e0f-68bf-43a0-9fba-aea97b
Publication of results
Published
Result
URL related to results and publications
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00097-4/fulltext
Number of participants that the trial has enrolled
131
Results
A total of 131 patients were included in the full analysis set (63 in the ubiquinol group, 68 in the placebo group). This study met the primary efficacy outcome (least square mean difference in the UMSARS part 2 score -1.7 [95% CI, -3.2 to -0.2]; P = 0.023).
Results date posted
| 2023 | Year | 04 | Month | 28 | Day |
Results Delayed
Results Delay Reason
Date of the first journal publication of results
| 2023 | Year | 04 | Month | 17 | Day |
Baseline Characteristics
Patients were recruited from among patients registered in the Japan MSA Registry (https://msajp.org/) who met all the following criteria: 1) probable or possible MSA; 2) able to walk 10 meters on their own or with walking aids; 3) had completed nucleotide sequence analysis of COQ2, and 4) 30 to 79 years of age.
Participant flow
Between June 26, 2018, and May 27, 2019, a total of 140 patients provided written informed consent, among whom 139 were randomly assigned to the ubiquinol group (n=69) or the placebo group (n=70). After the screening-observation period, 131 patients were prescribed with ubiquinol (n=63) or placebo (n=68). Two in the ubiquinol group discontinued the trial before the first efficacy assessment, resulting in the FAS of 61 and 68 patients in the ubiquinol and placebo groups, respectively.
Adverse events
There were no remarkable differences in the frequency of adverse events between the ubiquinol and placebo groups (Table 3). The frequency (95% CI) of patients with serious adverse events was 31.7% (20.6%, 44.7%) in the ubiquinol group, which was higher than that in the placebo group [17.6% (9.5%, 28.8%)].
Outcome measures
The LS mean change in the UMSARS Part 2 score from the baseline to 48 weeks were 5.4 in the ubiquinol group and 7.1 in the placebo group, which were significantly different (difference, -1.7; 95% confidence interval, -3.2 to -0.2). The changes from baseline to 48 weeks in Barthel index score, SARA score, and time required to walk 10 m were better in the ubiquinol group than in the placebo group.
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
Completed
Date of protocol fixation
| 2017 | Year | 12 | Month | 19 | Day |
Date of IRB
| 2017 | Year | 12 | Month | 19 | Day |
Anticipated trial start date
| 2018 | Year | 05 | Month | 02 | Day |
Last follow-up date
| 2020 | Year | 07 | Month | 10 | Day |
Date of closure to data entry
| 2020 | Year | 11 | Month | 06 | Day |
Date trial data considered complete
| 2021 | Year | 01 | Month | 26 | Day |
Date analysis concluded
| 2021 | Year | 03 | Month | 31 | Day |
Other
Other related information
Management information
Registered date
| 2018 | Year | 03 | Month | 16 | Day |
Last modified on
| 2023 | Year | 04 | Month | 28 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000036134
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| Registered date | File name |
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