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An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02090959
Recruitment Status : Completed
First Posted : March 19, 2014
Last Update Posted : June 10, 2019
Information provided by (Responsible Party):
PTC Therapeutics

Tracking Information
First Submitted Date  ICMJE March 17, 2014
First Posted Date  ICMJE March 19, 2014
Last Update Posted Date June 10, 2019
Actual Study Start Date  ICMJE March 31, 2014
Actual Primary Completion Date June 21, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2018)
  • Number of Participants With Adverse Events (AEs) [ Time Frame: Baseline (Day 1) to 6 weeks post-treatment (Week 150) ]
  • Number of Participants With Abnormalities in Laboratory Parameters [ Time Frame: Baseline (Day 1) to 6 weeks post-treatment (Week 150) ]
    Laboratory parameters include hematology and serum biochemistry parameters.
Original Primary Outcome Measures  ICMJE
 (submitted: March 17, 2014)
Long term safety of ataluren in boys with nonsense mutation dystrophinopathy, as determined by adverse events and laboratory abnormalities [ Time Frame: Baseline and 96 weeks ]
Change History Complete list of historical versions of study NCT02090959 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2018)
  • Change From Baseline in Ambulation at Week 144 , as Measured by the 6-Minute Walk Test (6MWT) [ Time Frame: Baseline, Week 144 ]
    The 6MWT is an established outcome measure reflecting the global status of all the systems involved in walking, including the neuromuscular, pulmonary, and cardiovascular systems. 6MWT represents an appropriate approach to assessing ambulatory ability in boys with duchenne and becker muscular dystrophy (DBMD).
  • Change From Baseline in Proximal Muscle Function at Week 144, as Assessed by Timed Function Tests (TMTs) [ Time Frame: Baseline, Week 144 ]
    TMTs include time to rise from supine position, time to run/walk 10 meters, and time to climb/descend 4 stairs.
  • Change From Baseline in Physical Function at Week 144, as Assessed by the North Star Ambulatory Assessment (NSAA) Score [ Time Frame: Baseline, Week 144 ]
    The NSAA consists of 17 activities, each scored as 0, 1, or 2. The sum of these 17 scores will be used to form a total score.
  • Change From Baseline in Motor Performance of the Upper Limb at Week 144, as Measured by the Performance Upper Limb (PUL) Score [ Time Frame: Baseline, Week 144 ]
    The PUL assessment includes 22 items (with an entry item to define starting functional level to avoid testing functional dimensions in which the participant lacks the lower limit of function, and 21 items subdivided into shoulder level (4 items), elbow level (9 items), and distal level (8 items) dimensions. Scoring varies across the scale between 0-1 to 0-6 according to performance. Each dimension will be scored separately with a maximum score of 16 for shoulder level, 34 for elbow level, and 24 for distal level. Total score will be calculated by adding the 3 level scores (maximum global score of 74).
  • Change From Baseline in Pediatric Outcomes Data Collection Instrument (PODCI) Transfers/Basic Mobility and Sports/Physical Functioning scores at Week 144 [ Time Frame: Baseline, Week 144 ]
  • Change From Baseline in Participant and Parent/Caregiver Reported Activities of Daily Living/Disease Status at Week 144 [ Time Frame: Baseline, Week 144 ]
  • Change From Baseline in Pulmonary Function at Week 144, as Measured by Spirometry [ Time Frame: Baseline, Week 144 ]
    Pulmonary function test will include forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1).
  • Ataluren Plasma Concentration [ Time Frame: Pre-dose at Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144 ]
    Pre-dose ataluren plasma concentrations prior to morning ataluren administration at each clinic visit will be assessed by a validated bioanalytical method.
  • Change From Baseline in Systolic and Diastolic Blood Pressure at Week 150 [ Time Frame: Baseline, Week 150 ]
  • Change From Baseline in Pulse Rate at Week 150 [ Time Frame: Baseline, Week 150 ]
  • Change From Baseline in Body Temperature at Week 150 [ Time Frame: Baseline, Week 150 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 17, 2014)
  • Physical Function [ Time Frame: Baseline and 96 weeks ]
    North Star Ambulatory Assessment,Timed Function Testing, Upper Limb Function, 6 Minute Walk Test
  • Patient and/or parent-reported activities of daily living and disease symptoms [ Time Frame: Baseline and 96 weeks ]
  • Quality of Life [ Time Frame: Baseline and 96 weeks ]
  • Pulmonary function [ Time Frame: Baseline and 96 weeks ]
  • Ataluren blood levels [ Time Frame: Baseline and 96 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy
Official Title  ICMJE A Phase 3 Extension Study of Ataluren (PTC124) in Patients With Nonsense Mutation Dystrophinopathy
Brief Summary

The primary objective of this study is to obtain long term safety data of ataluren in boys with nonsense mutation dystrophinopathy (who participated and completed a previous Phase 3 study of ataluren [PTC124-GD-020-DMD {NCT01826487}]) to augment the overall safety database. Screening and baseline procedures are structured to avoid a gap in treatment between the double-blind study (PTC124-GD-020-DMD) and this extension study.

This study may be further extended by amendment until either ataluren becomes commercially available or the clinical development of ataluren in duchenne muscular dystrophy (DMD) is discontinued.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Muscular Dystrophy, Duchenne
  • Muscular Dystrophies
  • Muscular Disorders, Atrophic
  • Muscular Diseases
  • Musculoskeletal Diseases
  • Neuromuscular Diseases
  • Nervous System Diseases
  • Genetic Diseases, X-Linked
  • Genetic Diseases, Inborn
Intervention  ICMJE Drug: Ataluren
Ataluren will be administered as per the dose and schedule specified in the arm.
Other Name: PTC124
Study Arms  ICMJE Experimental: Ataluren
Participants will receive ataluren oral suspension daily 10 milligrams per kilogram (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 144 weeks.
Intervention: Drug: Ataluren
Publications * Thangarajh M, Elfring GL, Trifillis P, McIntosh J, Peltz SW; Ataluren Phase 2b Study Group. The relationship between deficit in digit span and genotype in nonsense mutation Duchenne muscular dystrophy. Neurology. 2018 Sep 25;91(13):e1215-e1219. doi: 10.1212/WNL.0000000000006245. Epub 2018 Aug 22.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 30, 2017)
Original Estimated Enrollment  ICMJE
 (submitted: March 17, 2014)
Actual Study Completion Date  ICMJE June 21, 2018
Actual Primary Completion Date June 21, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Completion of study treatment in the previous Phase 3, double-blind study protocol (Protocol PTC124-GD-020-DMD).
  • Evidence of signed and dated informed consent/assent document(s) indicating that the participant (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial. Note: If the study candidate is considered a child under local regulation, a parent or legal guardian must provide written consent prior to initiation of study screening procedures and the study candidate may be required to provide written assent. The rules of the responsible Institutional Review Board/Independent Ethic Committee (IRB/IEC) regarding whether one or both parents must provide consent and the appropriate ages for obtaining consent and assent from the participant should be followed.
  • In participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the period of study drug administration and 6-week follow-up period.
  • Willingness and ability to comply with scheduled visits, ataluren administration plan, study procedures, laboratory tests, and study restrictions.

Exclusion Criteria:

  • Known hypersensitivity to any of the ingredients or excipients of the study drug (Litesse® UltraTM [refined polydextrose], polyethylene glycol 3350, Lutrol® micro F127 [poloxamer 407], mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, Cab-O-Sil® M5P [colloidal silica], magnesium stearate).
  • Ongoing participation in any other therapeutic clinical trial.
  • Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, electrocardiogram (ECG) findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 7 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Brazil,   Bulgaria,   Canada,   Chile,   Czechia,   France,   Germany,   Israel,   Italy,   Korea, Republic of,   Poland,   Spain,   Sweden,   Switzerland,   Turkey,   United Kingdom,   United States
Removed Location Countries Czech Republic
Administrative Information
NCT Number  ICMJE NCT02090959
Other Study ID Numbers  ICMJE PTC124-GD-020e-DMD
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party PTC Therapeutics
Study Sponsor  ICMJE PTC Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Francesco Bibbiani, M.D. PTC Therapeutics
PRS Account PTC Therapeutics
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP