Clinical trial NCT02819557: Study of Ataluren in ≥2 to <5 Year-Old Male Participants With Duchenne Muscular Dystrophy
Official title: A Phase 2 Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Ataluren (PTC124®) in Patients Aged ≥2 to <5 Years Old With Nonsense Mutation Dystrophinopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy
Lead sponsor: PTC Therapeutics
Sponsor class: INDUSTRY
First posted: 2016-06-30
Enrollment: 14
Sex: MALE
Minimum age (years): 2
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 2, multiple-dose, open-label study evaluating the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ataluren in participants aged ≥2 to \<5 years old with Duchenne muscular dystrophy (DMD) caused by a nonsense mutation in the dystrophin gene.

Detailed description: In nonsense mutation DMD (nmDMD), early start of treatment is important and necessary and, therefore, it is relevant to understand the correct and tolerable dose in this age group, particularly since ataluren is dosed by weight. This study included a 4-week screening period, a 52-week treatment period (the first 4 weeks of which included PK parameters), and a 4-week follow-up period for participants who completed the treatment period (60 weeks total duration). The objective of the extension period (treatment period after PK parameters have been completed) was to assess the long-term safety of chronic administration of ataluren in this participant population.

Eligibility criteria: Inclusion Criteria:

* Males ≥2 to \<5 years of age
* Body weight ≥12 kg
* Diagnosis of DMD
* Nonsense mutation in at least 1 allele of the dystrophin gene

Exclusion Criteria:

* Participation in any other drug or device clinical investigation
* Ongoing use of prohibited concomitant medications

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation, and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 56
measure: Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Biochemistry, Hematology, and Urinalysis) Parameter
timeFrame: Baseline up to Week 56
measure: Number of Participants With a Clinically Meaningful Abnormal Electrocardiogram (ECG) Test Results
timeFrame: Baseline up to Week 56
measure: Number of Participants With a Dose-Limiting Toxicity as Measured by Hepatic and Renal Toxicity
timeFrame: Baseline up to Week 56
Secondary outcomes:
measure: Pharmacokinetics: Maximum Observed Plasma Concentration From Time Zero up to 6 Hours After the Morning Dose (Cmax0-6hr)
timeFrame: 0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28
measure: Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration From Time Zero up to 6 Hours After the Morning Dose (Tmax0-6hr)
timeFrame: 0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28
measure: Area Under the Plasma Concentration Time Curve From Time Zero up to 10 Hours After the Morning Dose (AUC0-10hr)
timeFrame: 0 (predose), 1, 2, 4, 6, 8, and 10 (postdose) hours on Days 1 and 28
measure: Pharmacokinetics: Concentration at the End of the First (Morning) Dose Interval (Ctrough6hr)
timeFrame: 0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28
measure: Change From Baseline in Proximal Muscle Function as Assessed by Speed During TFTs
timeFrame: Baseline, Week 28 and Week 52
measure: Change From Baseline in Physical Function as Measured by the NSAA
timeFrame: Baseline, Week 28 and Week 52
measure: Change From Baseline in Height of Participants at Weeks 4, 16, 28, 40, 52, and 56
timeFrame: Baseline, Weeks 4, 16, 28, 40, 52, and 56
measure: Change From Baseline in Weight of Participants at Weeks 4, 16, 28, 40, 52, and 56
timeFrame: Baseline, Weeks 4, 16, 28, 40, 52, and 56
measure: Change From Baseline in Body Mass Index of Participants at Weeks 4, 16, 28, 40, 52, and 56
timeFrame: Baseline, Weeks 4, 16, 28, 40, 52, and 56
measure: Ataluren Palatability Characteristics as Determined by a Parent/Caregiver Questionnaire
timeFrame: Baseline up to Week 28
Other outcomes:
Locations:
city: Gulf Breeze
country: United States
facility: Child Neuro NWF
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Dallas
country: United States
facility: Children's Medical Center Dallas
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: PTC Therapeutics
name: Francesco Bibbiani, MD
role: STUDY_DIRECTOR
References: