Clinical Trial Results:
An Open-Label Study Evaluating the Safety and Pharmacokinetics of Ataluren in Children From ≥6 Months to <2 Years of Age with Nonsense Mutation Duchenne Muscular Dystrophy
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Summary
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EudraCT number |
2020-000980-21 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
07 Aug 2023
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Results information
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Results version number |
v2(current) |
This version publication date |
20 Apr 2024
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First version publication date |
23 Feb 2024
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Other versions |
v1 |
Version creation reason |
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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-048-DMD
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04336826 | ||
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 |
PTC Therapeutics, Inc., 100 Corporate Court, South Plainfield, United States, NJ 07080
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Public contact |
Medical Information, PTC Therapeutics International Limited, +353 19068700, medinfo@ptcbio.com
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Scientific contact |
Medical Information, PTC Therapeutics, Inc., +011 44 1-866-562-4620, medinfo@ptcbio.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000115-PIP01-07 | ||
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 |
07 Aug 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
07 Aug 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
07 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 |
The primary objective of this trial was to assess the safety and tolerability of ataluren in male children with nonsense mutation Duchenne muscular dystrophy (nmDMD) aged ≥6 months to <2 years old.
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Protection of trial subjects |
This study was designed and monitored in accordance with PTC Therapeutics (PTC) procedures,
which comply with the ethical principles of Good Clinical Practices (GCP) as required by the major regulatory authorities, and in accordance with the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Dec 2021
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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: 6
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Worldwide total number of subjects |
6
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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) |
6
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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) |
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 6 participants were screened and enrolled into the study. | ||||||||
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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 (mg)/kilogram (kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for up to 24 weeks. | ||||||||
Arm type |
Experimental | ||||||||
Investigational medicinal product name |
Ataluren
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Granules for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Ataluren was administered 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 (mg)/kilogram (kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for up to 24 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 (mg)/kilogram (kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for up to 24 weeks. | ||
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End point title |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [1] | ||||||
End point description |
An adverse event (AE) was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Serious adverse event (SAE): an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect, important medical event. A TEAE was defined as an AE that occurred or worsened while on ataluren (on or after first dose of ataluren) up to 4 weeks after the last dose. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the ‘Reported Adverse Events’ Section. Safety analysis set included all participants who received at least 1 dose of ataluren.
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End point type |
Primary
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End point timeframe |
Baseline up to Week 28
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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: The analysis was descriptive in nature. |
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| No statistical analyses for this end point | |||||||
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End point title |
Time to Maximum Plasma Concentration (Tmax) of Ataluren | ||||||||
End point description |
PK population included all participants who received at least 1 dose of ataluren and had 1 PK concentration datum.
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End point type |
Secondary
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End point timeframe |
Predose up to 12 hours postdose at Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Maximum Concentration (Cmax) of Ataluren | ||||||||
End point description |
PK population included all participants who received at least 1 dose of ataluren and had 1 PK concentration datum.
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End point type |
Secondary
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End point timeframe |
Predose up to 12 hours postdose at Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Trough Concentration (Ctrough) of Ataluren | ||||||||
End point description |
PK population included all participants who received at least 1 dose of ataluren and had 1 PK concentration datum. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Predose up to 12 hours postdose at Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) of Ataluren | ||||||||
End point description |
Pharmacokinetic (PK) population included all participants who received at least 1 dose of ataluren and had 1 PK concentration datum. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Predose up to 12 hours postdose at Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Area Under the Concentration-Time Curve Between Dosing Interval (AUC0-τ) of Ataluren | ||||||||
End point description |
PK population included all participants who received at least 1 dose of ataluren and had 1 PK concentration datum. Here, '99999' represents "Per prespecified analysis, 'Measure Type' and 'Method of Dispersion' were not estimable for this outcome measure because there were insufficient number of participants with data within the linear regression of concentration in the logarithmic scale versus time."
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End point type |
Secondary
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End point timeframe |
Predose up to 12 hours postdose at Week 24
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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 |
Baseline up to Week 28
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Adverse event reporting additional description |
Safety analysis set 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 |
26.0
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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 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for up to 24 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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29 Apr 2021 |
It included following changes:
• The duration of treatment was changed from “52 weeks” to “24 weeks” and the end of treatment (EOT) timepoint was updated to occur at Week 24 instead of Week 52.
• Removal of the efficacy endpoint (change in motor development).
• Removal of the exploratory endpoint “abnormalities of physical findings, clinical laboratory tests, or electrocardiograms (ECGs)” since this information is captured as part of the primary endpoint.
• The exploratory objective of “to assess changes from baseline in creatine kinase (CK) levels after 24 weeks of ataluren treatment” and the exploratory endpoint of “change from baseline in CK levels” were added.
• Updates were made to the volume and process by which blood PK samples are collected. |
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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 | |||
