Clinical trial NCT01140451: Extension Study of Ataluren (PTC124) in Cystic Fibrosis
Official title: A Phase 3 Extension Study of Ataluren (PTC124®) in Subjects With Nonsense-Mutation-Mediated Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: PTC Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2010-06-09
Enrollment: 191
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Cystic fibrosis (CF) is a genetic disorder caused by a mutation in the gene that makes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A specific type of mutation called a nonsense (premature stop codon) mutation is the cause of CF in approximately 10% of patients with the disease. Ataluren is an orally delivered investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 3 extension trial that will evaluate the long-term safety of ataluren in adult and pediatric participants with nonsense mutation CF (nmCF), as determined by adverse events and laboratory abnormalities. The study will also assess changes in pulmonary function, CF pulmonary exacerbations, health-related quality of life, antibiotic use for CF-related infections, CF-related disruptions to daily living, body weight, and CF pathophysiology. Funding source for this study is the FDA OOPD.

Detailed description: This Phase 3, open-label, safety and efficacy study will be performed at sites in North America, Europe, and Israel. The study will enroll up to approximately 208 participants with nmCF who participated in a previous Phase 3 study of ataluren (PTC124-GD-009-CF \[Study 009\], NCT00803205). Participants will receive study drug 3 times per day (TID) (at breakfast, lunch, and dinner) for approximately 48 weeks (approximately 1 year). Study assessments will be performed at clinic visits every 8 weeks.

Eligibility criteria: Inclusion Criteria:

* Completion of blinded study drug treatment in the previous Phase 3 study (PTC124-GD-009-CF).
* Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if \<18 years of age).
* In participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during ataluren administration and the 4-week follow up period.
* Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.

Exclusion Criteria:

* Known hypersensitivity to any of the ingredients or excipients of the study drug (list provided at study sites).
* Current pregnancy or lactating, or pregnancy or lactating during the previous Phase 3 study.
* 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, 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.

Primary outcomes:
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline (Week 1 [Total Study Week 48]) up to 4 Weeks Post-Treatment (Week 100 [Total Study Week 148]) or Premature Discontinuation (PD) (whichever occurred first)
measure: Number of Participants With Any Treatment-Emergent Laboratory Abnormality (TELA)
timeFrame: Baseline (Week 1 [Total Study Week 48]) up to 4 Weeks Post-Treatment (Week 100 [Total Study Week 148]) or PD (whichever occurred first)
Secondary outcomes:
measure: Percentage of Predicted Function (Percent-Predicted) of Forced Expiratory Volume in 1 Second (FEV1) at Baseline
timeFrame: Baseline (Week 1 [Total Study Week 48])
measure: Percentage Change From Baseline in Percent-Predicted of FEV1 at Weeks 48 and 96
timeFrame: Week 48 (Total Study Week 96), End of Treatment (EOT) (Week 96 [Total Study Week 144])
measure: Percent-Predicted of Forced Vital Capacity (FVC) at Baseline
timeFrame: Baseline (Week 1 [Total Study Week 48])
measure: Percentage Change From Baseline in Percent-Predicted of FVC at Weeks 48 and 96
timeFrame: Week 48 (Total Study Week 96), EOT (Week 96 [Total Study Week 144])
measure: Percent-Predicted of Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) at Baseline
timeFrame: Baseline (Week 1 [Total Study Week 48])
measure: Percentage Change From Baseline in Percent-Predicted of FEF25-75 at Weeks 48 and 96
timeFrame: Week 48 (Total Study Week 96), EOT (Week 96 [Total Study Week 144])
measure: Number of Participants With Pulmonary Exacerbations as Defined by Modified Fuch's Criteria
timeFrame: Baseline (Week 1 [Total Study Week 48]) up to Week 48 and EOT (Week 96) (Total Study Weeks 96 and 144)
measure: Rate of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Over 48 Weeks
timeFrame: Baseline (Week 1 [Total Study Week 48]) up to Week 48 (Total Study Week 96)
measure: Duration of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria
timeFrame: Weeks 43 up to 48 and Weeks 91 up to 96 (Total Study Weeks 91 up to 96 and Weeks 139 up to 144)
measure: Number of Participants With Severe Pulmonary Exacerbations as Defined by Modified Fuch's Criteria
timeFrame: Weeks 43 up to 48 and Weeks 91 up to 96 (Total Study Weeks 91 up to 96 and Weeks 139 up to 144)
measure: Change From Baseline for the Respiratory Domain Score of the Cystic Fibrosis (CF) Questionnaire-Revised (CFQ-R) at Weeks 48 and 96
timeFrame: Baseline (Week 1 [Total Study Week 48]), Week 48 (Total Study Week 96), EOT (Week 96 [Total Study Week 144])
measure: Rate of Study Drug Compliance
timeFrame: Baseline (Week 1 [Total Study Week 48]) up to EOT (Week 96 [Total Study Week 144])
measure: Predose Concentration of Ataluren
timeFrame: Predose at Weeks 1, 16, 32, 48, 64, 80 and EOT (Week 96) (Total Study Weeks 48, 64, 80 96, 112, 128, and 144, respectively)
measure: Number of Participants Who Required Interventions for Pulmonary Symptoms
timeFrame: Baseline (Week 1 [Total Study Week 48]) up to EOT (Week 96 [Total Study Week 144])
measure: Number of Participants With Disruptions in Activities of Daily Living Because of Pulmonary Symptoms
timeFrame: Baseline (Week 1 [Total Study Week 48]) up to EOT (Week 96 [Total Study Week 144])
measure: Duration of Disruptions in Activities of Daily Living Because of Pulmonary Symptoms
timeFrame: Baseline (Week 1 [Total Study Week 48]) up to EOT (Week 96 [Total Study Week 144])
measure: Change From Baseline in Body Weight at Weeks 48 and 96
timeFrame: Baseline (Week 1 [Total Study Week 48]), Week 48 (Total Study Week 96), EOT (Week 96 [Total Study Week 144])
measure: Change From Baseline in Body Mass Index (BMI) at Weeks 48 and 96
timeFrame: Baseline (Week 1 [Total Study Week 48]), Week 48 (Total Study Week 96), EOT (Week 96 [Total Study Week 144])
measure: Total Lung Computed Tomography (CT) Score at Weeks 48 and 96
timeFrame: Week 48 (Total Study Week 96) and EOT (Week 96 [Total Study Week 144])
measure: Change From Baseline in the Nasal Transepithelial Potential Difference (TEPD) at Week 48
timeFrame: Baseline (Week 1 [Total Study Week 48]) and Week 48 (Total Study Week 96)
measure: Change From Baseline in the Concentration of Sweat Chloride at Week 48
timeFrame: Baseline (Week 1 [Total Study Week 48]), Week 48 (Total Study Week 96)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama-Birmingham
state: Alabama
city: Long Beach
country: United States
facility: Miller Children's Hospital Long Beach
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital
state: California
city: Aurora
country: United States
facility: The Children's Hospital
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University Cystic Fibrosis Center
state: Georgia
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Children's Center
state: Maryland
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: St. Vincent's Hospital
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Cleveland
country: United States
facility: Rainbow Babies & Children's Hospital
state: Ohio
city: Pittsburgh
country: United States
facility: Childrens Hospital of Pittsburgh
state: Pennsylvania
city: Brussels
country: Belgium
facility: Hôpital Erasme
city: Brussels
country: Belgium
facility: Hôpital Universitaire des Enfants Reine Fabiola
city: Brussels
country: Belgium
facility: University Hospital Brussels
city: Leuven
country: Belgium
facility: University Hospital Leuven
city: Toronto
country: Canada
facility: University of Toronto
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Necker - Enfants Malades
city: Toulouse
country: France
facility: Hôpital des Enfants
city: Köln
country: Germany
facility: Klinikum der Universität Köln
city: Jerusalem
country: Israel
facility: Hadassah University Hospital - Mount Scopus
city: Roma
country: Italy
facility: Università La Sapienza
city: Verona
country: Italy
facility: Azienda Ospedaliera di Verona
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Stockholm
country: Sweden
facility: Karolinska University Hospital, Huddinge
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
Study officials:
affiliation: PTC Therapeutics, Inc.
name: Temitayo Ajayi, MD
role: STUDY_DIRECTOR
References: