Clinical Trial Results:
A Phase 3, Multi-center, Open-label, Safety Study of Oral Edaravone Administered over 48 Weeks in Subjects with Amyotrophic Lateral Sclerosis (ALS)
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Summary
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EudraCT number |
2019-002108-41 |
Trial protocol |
DE IT |
Global end of trial date |
07 Oct 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Aug 2023
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First version publication date |
26 Aug 2023
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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-A01
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Additional study identifiers
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ISRCTN number |
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US NCT number |
NCT04165824 | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
Japan Registry of Clinical Trials (jRCT): jRCT2080224982 | ||
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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 Blvd, Suite 1100, Jersey City, United States, 07310
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Public contact |
General Information, Mitsubishi Tanabe Pharma Europe Ltd, regulatory@mt-pharma-eu.com
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Scientific contact |
General Information, Mitsubishi Tanabe Pharma Europe Ltd, 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 |
24 Nov 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
07 Oct 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Oct 2021
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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 and tolerability of Oral Edaravone in subjects with ALS over 24 and 48 weeks.
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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 |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Nov 2019
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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 |
Italy: 9
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Country: Number of subjects enrolled |
Japan: 65
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Country: Number of subjects enrolled |
United States: 71
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Country: Number of subjects enrolled |
Canada: 23
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Country: Number of subjects enrolled |
France: 11
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Country: Number of subjects enrolled |
Germany: 6
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Worldwide total number of subjects |
185
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EEA total number of subjects |
26
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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) |
120
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From 65 to 84 years |
65
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment Started on 26 Nov 2019 and was completed on 29 Oct 2020, globally: USA, Canada, Germany, Italy, France, Japan Subjects Screened: 216 Screen Failures: 31 Subjects Enrolled in Study: 185 Subjects who completed week 48: 139 Subjects who discontinued during week 48: 46 | ||||||||||||||||
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Pre-assignment
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Screening details |
Subjects were screened globally following protocol specific inclusion and exclusion criteria Subjects Screened: 216 Screen Failures: 31 Reason for Screen Failure Study Entry Criteria Not Met (25) Withdrawal by Subjects (2) Covid 19 (4) | ||||||||||||||||
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Period 1
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Period 1 title |
MT-1186-A01 (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 | ||||||||||||||||
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Arms
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Arm title
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MT-1186 | ||||||||||||||||
Arm description |
MT-1186 105mg (2 weeks On/Off ) | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
MT-1186
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Investigational medicinal product code |
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Other name |
Edaravone
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Pharmaceutical forms |
Suspension for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
MT-1186 oral suspension (21 mg/mL) in amber multi-use bottles, adapters, and oral syringes were provided for each subject, for the duration of their participation in the study. Suspension bottles contained approximately 735 mg of MT-1186 in 35 mL for the first cycle and approximately 1050 mg of MT-1186 in 50 mL for Cycles 2 through 12.
All subjects enrolled received the following dose regimen:
* An initial treatment cycle with daily dosing for 14 days, followed by a 14-day drug-free period.
* Subsequent treatment cycles with daily dosing for 10 days out of 14-day periods, followed by 14-day drug-free periods. Treatment cycles were every 4 weeks.
The dose of MT-1186 was taken after an overnight fast and subjects continued to fast at least 1 to 2 hours postdose before the next meal (eg, breakfast)
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Baseline characteristics reporting groups
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Reporting group title |
MT-1186-A01
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Full Analysis
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Analysis Population:
Enrolled Population: The enrolled population set is all subjects who were found eligible and signed ICF to participate in the study.
Safety Analysis Population: The safety analysis population set is defined as all enrolled subjects who received at least 1 dose of oral edaravone
Pharmacokinetic (PK) Population: PK population includes all subjects who receive at least 1 dose of oral edaravone and who have at least 1 post-dose value for plasma concentration without important protocol deviations which may affect the PK of oral edaravone.
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End points reporting groups
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Reporting group title |
MT-1186
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Reporting group description |
MT-1186 105mg (2 weeks On/Off ) | ||
Subject analysis set title |
Full Analysis
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Analysis Population:
Enrolled Population: The enrolled population set is all subjects who were found eligible and signed ICF to participate in the study.
Safety Analysis Population: The safety analysis population set is defined as all enrolled subjects who received at least 1 dose of oral edaravone
Pharmacokinetic (PK) Population: PK population includes all subjects who receive at least 1 dose of oral edaravone and who have at least 1 post-dose value for plasma concentration without important protocol deviations which may affect the PK of oral edaravone.
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End point title |
Number of Participants with Treatment Emergent Adverse Events [1] | |||||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
48 Weeks
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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: This study is a long-term, open-label safety study. As a result, no formal hypothesis testing is planned for this study. The long-term safety and tolerability of oral edaravone was evaluated in exploratory manner using descriptive statistics. For exploratory efficacy analysis, point estimates and their associated 95% Confidence Interval was presented. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Number of Treatment Emergent Adverse Events [2] | |||||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
48 Weeks
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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: This study is a long-term, open-label safety study. As a result, no formal hypothesis testing is planned for this study. The long-term safety and tolerability of oral edaravone was evaluated in exploratory manner using descriptive statistics. For exploratory efficacy analysis, point estimates and their associated 95% Confidence Interval was presented. |
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End point title |
Time to Death, Tracheostomy or Permanent Assisted Mechanical Ventilation | |||||||||||||||||||||
End point description |
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End point type |
Other pre-specified
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End point timeframe |
48 Weeks
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Adverse events information
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Timeframe for reporting adverse events |
48 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
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Reporting group description |
MT-1186 105mg (2 weeks On/Off ) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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23 Dec 2019 |
Significant changes included in this amendment are summarized below:
• Provided additional information to clinical sites regarding dosing cycles/study days
• Clarified discrepancies within the protocol
• Corrected formatting and spelling throughout |
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26 Feb 2020 |
The amendment clarified discrepancies within the protocol and corrected formatting and spelling throughout. |
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23 Sep 2020 |
Significant changes included in this amendment are summarized below:
• Updated with impacts of COVID-19, including delayed completion date, and risks and precautions taken
• Clarified discrepancies within the protocol
• Updated personnel information
• Updated introduction with information from recent studies
• Updated with current and revised guidelines
• Corrected formatting and spelling throughout |
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16 Apr 2021 |
Significant changes included in this amendment are summarized below:
• Contraceptive guidance in Appendix 2 was updated to align with the Germany-specific protocol.
• Editorial changes were made to allow PEG/RIG dosing.
• The sample size was increased to compensate for potential increased premature terminations due to COVID-19, to ensure at least 100 completers at 48 weeks of treatment.
• Due to COVID-19 restrictions related to site visits, it was clarified that formal telehealth would not be used, but instead home nursing visits or telephone calls for questionnaires would be conducted.
• It was clarified that any combination of phenylbutyrate and tauroursodeoxycholic acid was prohibited throughout the study. |
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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 | |||
