A Phase 3 Extension Study of Ataluren (PTC124) in Patients With Nonsense Mutation Dystrophinopathy
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- PTC Therapeutics
- Enrollment
- 219
- Locations
- 58
- Primary Endpoint
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Study Overview
Brief Summary
The primary objective of this study is to obtain long term safety data of ataluren in male participants 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 7 Years to 15 Years (Child)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Completion of study treatment in the previous Phase 3, double-blind study (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 1 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], and 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.
Arms & Interventions
Ataluren
Participants will receive ataluren suspension orally 3 times a day (TID), 10 milligrams/kilogram (mg/kg) at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for up to 144 weeks.
Intervention: Ataluren (Drug)
Outcomes
Primary Outcomes
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Baseline (Day 1) up to 6 weeks post-treatment (Week 150)
An adverse event (AE): any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of AEs: graded per Common Terminology Criteria for AEs (CTCAE), Version 3.0 as Grade 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). Drug-related AEs: AEs with possible, probable, unlikely relationship, or unrelated to study drug. Serious AEs (SAEs): death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention. TEAE: an AE that occurred or worsened in the period extending from first dose of study drug in this study to 6 weeks after last dose of study drug in this study. A summary of other non-serious AEs and all SAEs, regardless of causality is located in Reported AE section.
Number of Participants With Abnormalities in Clinical Laboratory Parameters
Time Frame: Baseline (Day 1) up to 6 weeks post-treatment (Week 150)
Abnormalities in laboratory variables as pre-defined in protocol for safety-monitoring were: Hepatic (Serum alanine aminotransferase \[ALT\]: increase of greater than \[\>\] 150 units/liter \[U/L\] with stable or decrease of creatinine kinese \[CK\]; Serum glutamyl amino transferase \[GGT\] \[U/L\]: Grade 2 \[\>2.5 - 5.0 \* upper limit of normal {ULN}\]), renal (Serum cystatin C miiligrams/liter \[mg/L\] \>1.33 - 2.00 mg/L; Serum blood urea nitrogen \[UREAN\] \[millimoles/liter {mmol/L}\] greater than or equal to \[≥\]1.5 - 3.0 \* ULN; Urine occult blood: 2+ \[Small\], 3+ \[Moderate\], 4+ \[Large\]), and electrolytes (Serum sodium: low \[mmol/L\], Grade 3-4 \[less than {\<}130 mmol/L\]; serum potassium: high \[mmol/L\], Grade 3-4 \[\>6.0 mmol/L\]; and Serum bicarbonate \[mmol/L\]: Grade 2 \[\<16 - 11 mmol/L\]).
Secondary Outcomes
- Change From Baseline in PEF as Measured by Spirometry at Week 144(Baseline, Week 144)
- Change From Baseline in PCF as Measured by Spirometry at Week 144(Baseline, Week 144)
- Change From Baseline in 6MWD at Week 144(Baseline, Week 144)
- Change From Baseline in Time to Descend 4 Stairs at Week 144(Baseline, Week 144)
- Change From Baseline in Time to Stand From Supine Position at Week 144(Baseline, Week 144)
- Change From Baseline in Time to Walk/Run 10 Meters at Week 144(Baseline, Week 144)
- Change From Baseline in Time to Climb 4 Stairs at Week 144(Baseline, Week 144)
- Change From Baseline in Physical Function Total Score as Measured by NSAA at Week 144(Baseline, Week 144)
- Change From Baseline in PUL Total Score at Week 144(Baseline, Week 144)
- Change From Baseline in Percent Predicted FVC as Measured by Spirometry at Week 144(Baseline, Week 144)
- Change From Baseline in Percent Predicted FEV1 as Measured by Spirometry at Week 144(Baseline, Week 144)
- Change From Baseline in PODCI Transfers/Basic Mobility Score at Week 144(Baseline, Week 144)
- Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel(Baseline, Week 144)
- Ataluren Plasma Concentration(Pre-dose at Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 144)
- Change From Baseline in Systolic and Diastolic Blood Pressure at Week 144(Baseline, Week 144)
- Change From Baseline in Pulse Rate at Week 144(Baseline, Week 144)
- Change From Baseline in Body Temperature at Week 144(Baseline, Week 144)