Clinical Trial Results:
A Phase 3, Multi-center, Open-label, Safety Extension Study of Oral Edaravone Administered over 96 Weeks in Subjects with Amyotrophic Lateral Sclerosis (ALS)
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Summary
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EudraCT number |
2020-000376-38 |
Trial protocol |
FR DE IT |
Global end of trial date |
09 Aug 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Aug 2024
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First version publication date |
14 Aug 2024
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MT-1186-A03
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Additional study identifiers
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ISRCTN number |
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US NCT number |
NCT04577404 | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
jRCT: jRCT2041200084 | ||
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Sponsors
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Sponsor organisation name |
Mitsubishi Tanabe Pharma America Inc.
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Sponsor organisation address |
525 Washington Boulevard, Suite 1100, Jersey City, New Jersey, United States, 07310
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Public contact |
General Information, Mitsubishi Tanabe Pharma Europe Ltd, +44 2070655000, regulatory@mt-pharma-eu.com
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Scientific contact |
General Information, Mitsubishi Tanabe Pharma Europe Ltd, +44 2070655000, regulatory@mt-pharma-eu.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
09 Aug 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Aug 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Aug 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the long-term safety of oral edaravone at a dose of 105 mg administered once daily for 10 days out of a 14-day period, followed by a 14-day drug-free period for 96 weeks of treatment or until the drug is commercially available in that country.
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Protection of trial subjects |
The study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice as required by the International Conference on Harmonization guidelines, applicable regional and local legislation, and standard operating procedures in place at Mitsubishi Tanabe Pharma America Inc and at the contracted vendor. All participants underwent screening aimed at minimizing the likelihood and impact of potential risks of MT-1186. In addition, regular safety monitoring during the study period for all participants ensured that any unanticipated effects of study participation were identified promptly and managed appropriately. Risk minimization measures were also employed during the study as per the risk-benefit assessment for potential anticipated risks. A participant was to be withdrawn from the study if ANY of the protocol specific withdrawal criteria were met including voluntary wish of participant to withdraw from further participation.
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Oct 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 38
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Country: Number of subjects enrolled |
Canada: 18
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Country: Number of subjects enrolled |
Japan: 50
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Country: Number of subjects enrolled |
France: 8
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Country: Number of subjects enrolled |
Germany: 5
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Country: Number of subjects enrolled |
Italy: 5
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Worldwide total number of subjects |
124
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EEA total number of subjects |
18
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
84
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From 65 to 84 years |
40
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment started on 29 Oct 2020 and was completed on 10 Feb 2023. Recruitment was conducted globally in the USA, Canada, Germany, Italy, France and Japan. | ||||||||||||||||||||
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Pre-assignment
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Screening details |
There was no screening period since the subjects who completed the treatment in the study MT-1186-A01 and met the eligibility criteria were enrolled into this open-label treatment study (MT-1186-A03). Day 1 is equal to the Week 48 visit of the MT-1186-A01 study. | ||||||||||||||||||||
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Period 1
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Period 1 title |
MT-1186-A03 (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||
Blinding implementation details |
This is an open-label study. Therefore, no randomization or blinding is applicable.
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Arms
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Arm title
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MT-1186 105mg (2 weeks On/Off ) | ||||||||||||||||||||
Arm description |
Subjects who met eligibility criteria were enrolled into this open-label treatment study (MT-1186-A03) and continued to receive 105 mg of edaravone once daily following an overnight fast, and subjects continued to fast for at least 1 to 2 hours before the next meal (e.g., breakfast). Treatment cycles occurred every 28 days (10 days on study drug out of a 14-day period, followed by 14 days off study drug). | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
edaravone (MT-1186)
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Investigational medicinal product code |
MT-1186
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Other name |
Edaravone
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received an oral dose of edaravone 105 mg suspension. Each treatment cycle included daily dosing for 10 days out of a 14-day period, followed by a 14-day drug-free period. Treatment cycles were every 4 weeks. The dose of edaravone was taken after an overnight fast and subjects continued to fast for at least 1 to 2 hours post-dose before the next meal (e.g., breakfast).
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Baseline characteristics reporting groups
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Reporting group title |
MT-1186-A03 (overall period)
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
MT-1186 105mg (2 weeks On/Off )
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Reporting group description |
Subjects who met eligibility criteria were enrolled into this open-label treatment study (MT-1186-A03) and continued to receive 105 mg of edaravone once daily following an overnight fast, and subjects continued to fast for at least 1 to 2 hours before the next meal (e.g., breakfast). Treatment cycles occurred every 28 days (10 days on study drug out of a 14-day period, followed by 14 days off study drug). | ||
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End point title |
Number of Treatment-Emergent Adverse Events [1] | ||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
All AEs, regardless of the relationship to IMP, occurring from the time written ICF were obtained from a subject until the end of the safety Follow-up Period or the withdrawal of the subject from the study.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were performed since the primary end points are the number of TEAEs and the number of patients with TEAEs. Considering the nature of those primary endpoints statistical analysis was not needed. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of participants with Treatment Emergent Adverse Events [2] | ||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
All AEs, regardless of the relationship to IMP, occurring from the time written ICF were obtained from a subject until the end of the safety Follow-up Period or the withdrawal of the subject from the study.
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were performed since the primary end points are the number of TEAEs and the number of patients with TEAEs. Considering the nature of those primary endpoints statistical analysis was not needed. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of Adverse Drug Reactions [3] | ||||||
End point description |
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End point type |
Primary
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End point timeframe |
All AEs, regardless of the relationship to IMP, occurring from the time written ICF were obtained from a subject until the end of the safety Follow-up Period or the withdrawal of the subject from the study.
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were performed since the primary end points are the number of ADR and the number of patients with ADR. Considering the nature of those primary endpoints statistical analysis was not needed. |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants with Adverse Drug Reactions [4] | ||||||
End point description |
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End point type |
Primary
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End point timeframe |
All AEs, regardless of the relationship to IMP, occurring from the time written ICF were obtained from a subject until the end of the safety Follow-up Period or the withdrawal of the subject from the study.
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were performed since the primary end points are the number of ADR and the number of patients with ADR. Considering the nature of those primary endpoints statistical analysis was not needed. |
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| No statistical analyses for this end point | |||||||
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Adverse events information
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Timeframe for reporting adverse events |
96 weeks
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
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Reporting groups
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Reporting group title |
MT-1186 105 mg (2 Weeks On/Off)
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Reporting group description |
Subjects who met eligibility criteria were enrolled into this open-label treatment study (MT-1186-A03) and continued to receive 105 mg of edaravone once daily following an overnight fast, and subjects continued to fast for at least 1 to 2 hours before the next meal (e.g., breakfast). Treatment cycles occurred every 28 days (10 days on study drug out of a 14-day period, followed by 14 days off study drug). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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12 Nov 2021 |
Significant changes included in this amendment are summarized below:
・Study completion delayed due to COVID-19.
・Removed a reference to the screening in exclusion criterion 2.
・Removed pregnancy or lactation as exclusion criterion.
・Added respiratory rate to vital sign measurements.
・Updated text on clinical pharmacology for studies MT-1186-J04, MT-1186-J05, and MT-1186-J06.
・Clarified route of administration as oral/PEG/RIG. |
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23 Dec 2022 |
The amendment clarified discrepancies within the protocol and corrected formatting and spelling throughout.
・Updated the anticipated number of subjects who completed study MT-1186-A01 and who were eligible for this extension study from 100 to 140.
・Clarified that physical examinations should include neurological examinations.
・Clarified how the exploratory efficacy analysis would be performed.
・Added medication compliance assessment to schedule of assessments in place of the eDiary.
・Revised to reflect completion of study MT-1186-J05 and added information for study MT-1186-Z-101.
・Updated to allow for PEG/RIG dosing as the subjects’ disease progressed to align with removal of the eDiary.
・Clarified that screen failures cannot be enrolled in the study.
・Clarified the definition of noncompliance.
・Clarified that the study can be prematurely terminated and timing of the EOT visit.
・Clarified expectations due to COVID-19 impacts on study visits and patient safety.
・Clarified that the use of COVID-19 vaccines are allowed as permitted and concomitant medications.
・Clarified that subjects discontinue study treatment and that phone calls are to be aligned with clinic visits and are to determine if death, tracheostomy, or permanent assisted mechanical ventilation occurred. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
