Clinical Trial Results:
Phase 2 Clinical Pharmacology Study to Assess Dystrophin Levels in Subjects With nmDMD Before and After Treatment with Ataluren
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Summary
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EudraCT number |
2019-001767-67 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
23 Oct 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Apr 2022
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First version publication date |
30 Apr 2022
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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 |
PTC124-GD-045-DMD
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03648827 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
PTC Therapeutics, Inc.
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Sponsor organisation address |
100 Corporate Court, South Plainfield, United States, NJ 07080
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Public contact |
Medical Information, PTC Therapeutics, Inc., +011 44 1-866-562-4620, medinfo@ptcbio.com
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Scientific contact |
Medical Information, PTC Therapeutics International Limited, +353 19068700, medinfo@ptcbio.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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
23 Oct 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
23 Oct 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Oct 2020
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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 |
The main objective of the trial was to assess the change in levels of dystrophin in ambulatory participants with nonsense mutation Duchenne Muscular Dystrophy (nmDMD) after treatment with ataluren for 40 weeks using quantitative assay, such as electrochemiluminescence (ECL).
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Protection of trial subjects |
The study was conducted in accordance with the ethical principles that have their origins in the Declaration of Helsinki (revised version of Edinburgh, Scotland, 2000) and in conformance with
the International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidance documents.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 Dec 2018
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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: 20
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Worldwide total number of subjects |
20
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EEA total number of subjects |
0
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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) |
20
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||
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Pre-assignment
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Screening details |
A total of 21 participants were screened, one of whom did not meet eligibility criteria. The remaining 20 participants who signed the informed consent and were not screen failures comprise the Enrolled Population. | ||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||
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Arms
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Arm title
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Ataluren | ||||||||
Arm description |
Participants received ataluren oral suspension 10 milligrams per kilogram (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for 40 weeks. | ||||||||
Arm type |
Experimental | ||||||||
Investigational medicinal product name |
Ataluren
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Investigational medicinal product code |
PTC124
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Other name |
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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 |
Ataluren was administered as per the dose and schedule specified in the arm description.
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Baseline characteristics reporting groups
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Reporting group title |
Ataluren
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Reporting group description |
Participants received ataluren oral suspension 10 milligrams per kilogram (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for 40 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Ataluren
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Reporting group description |
Participants received ataluren oral suspension 10 milligrams per kilogram (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for 40 weeks. | ||
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End point title |
Percent Change From Baseline in Dystrophin Level at Week 40, as Measured by ECL [1] | ||||||||
End point description |
The percent change in dystrophin level from baseline in ambulatory nonsense mutation duchenne muscular dystrophy (nmDMD) participants after treatment with ataluren for 40 weeks was analyzed using quantitative assay (ECL).The least square (LS) mean and 90% confidence interval (CI) were analyzed from a mixed-model repeated measures (MMRM) with factors of muscle locations and visits as fixed effects, and participants as a random effect. Intent-to-treat (ITT) population included all enrolled participants with a valid assessment of dystrophin level at baseline, as measured by ECL.
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End point type |
Primary
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End point timeframe |
Baseline, Week 40
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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: Statistical analysis was not planned for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percent Change From Baseline in Dystrophin Level at Week 40, as Determined by Immunohistochemistry (IHC) Membrane Stain Density | ||||||||
End point description |
The percent change in dystrophin level from baseline in ambulatory nmDMD participants after 40 weeks of ataluren therapy was determined by IHC membrane stain density. The LS mean and 90% CI were analyzed from an MMRM with factors of muscle locations and visits as fixed effects, and participants as a random effect. ITT population included all enrolled participants with a valid assessment of dystrophin level at baseline, as measured by ECL.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 40
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to Week 40
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Adverse event reporting additional description |
Safety Population included all participants who received at least 1 dose of ataluren.
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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 |
23.1
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Reporting groups
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Reporting group title |
Ataluren
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Reporting group description |
Participants received ataluren oral suspension 10 milligrams per kilogram (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for 40 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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22 Oct 2018 |
The changes implemented with this amendment are: - Text was added in objectives to clarify that secondary and exploratory objective assessments and endpoints will be collected after 40 weeks of ataluren treatment. An exploratory objective was added to evaluate pharmacokinetics of ataluren at 40 weeks of treatment. - Text was added in endpoints to clarify that exploratory endpoints will be collected after 40 weeks of ataluren treatment. An exploratory endpoint was added to evaluate pharmacokinetics of ataluren at Week 1 and Week 40 of ataluren of treatment. - The age of participants that will be included from the study was increased to >2 and <8 years of age from <7 years of age to increase study enrollment. - Removed that phenotypic evidence of DMD must be evident by 6 years of age. - Pharmacokinetic (PK) sampling was added for pharmacokinetic evaluation. For Visit 1, samples will be drawn pre-first study dose and 2 hours postdose, and on Visit 3 will be drawn pre-morning dose and 2 hours postdose. - Visit 2 was changed from Week 19 to Week 20. - The location of the biopsies was changed from right vastus lateralis and right tibialis anterior muscles to the biceps and gastrocnemius muscles. If the bicep muscle is considered by the investigator to be too small for a biopsy sample, the right tibialis anterior muscle may be used. - The text was revised from 9-month treatment period to a 40-week treatment period. |
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06 May 2019 |
The changes implemented with this amendment are: - Exploratory endpoints: deleted specific PK parameters. - Revised from 3 muscle biopsy samples to up to approximately 450 mg of muscle tissue (up to 4 cores per muscle); allowed sample from the right tibialis anterior muscle if obtained sample is not evaluable for analysis. - Extended screening window from 30 to 45 days; added details for assessing height/weight and physical exams, deleted details of PK analyses. - Added information on Cardiac Drugs for Cardiomyopathy Prophylaxis/Treatment. |
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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 | |||
