Clinical trial NCT02107859: Study of Ataluren (PTC124) in Cystic Fibrosis
Official title: An Open-Label Safety and Efficacy Study for Patients With Nonsense Mutation Cystic Fibrosis Previously Treated With Ataluren (PTC124)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Cystic Fibrosis
Keywords: Cystic fibrosis
Nonsense mutation
Premature stop codon
PTC124
Ataluren
Lead sponsor: PTC Therapeutics
Sponsor class: INDUSTRY
First posted: 2014-04-08
Enrollment: 61
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to determine the long-term safety and tolerability of ataluren in participants with nonsense mutation cystic fibrosis (nmCF) who completed participation in the double-blind study PTC124-GD-009-CF (NCT00803205), as assessed by adverse events and laboratory abnormalities. The secondary objective of this study includes the assessment of the efficacy of ataluren, as measured by forced expiratory volume in 1 second (FEV1) and pulmonary exacerbation rate, and other safety parameters (for example, 12-lead electrocardiogram \[ECG\] measurements, vital signs).


Eligibility criteria: Key Inclusion Criteria:

* Ability to provide written informed consent (parental/guardian consent and participant assent if less than \[\<\] 18 years of age).
* Evidence of completed participation in the double-blind study, PTC124-GD-009-CF (Study 009).
* Body weight greater than or equal to (≥) 16 kilograms (kg).
* Performance of a valid, reproducible spirometry test using the study-specific spirometer during the screening period.
* Confirmed laboratory values within the central laboratory ranges at screening.
* In male and female participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and 60-day follow-up period.
* Willingness and ability to comply with all study procedures and assessments, including scheduled visits, drug administration plan, laboratory tests, and study restrictions.

Key Exclusion Criteria:

* Chronic use of systemic tobramycin within 4 weeks prior to screening.
* Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection (including viral illnesses) within 3 weeks prior to screening or between screening and randomization.
* Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or re-initiation) in a chronic treatment/prophylaxis regimen for CF or for CF-related conditions within 4 weeks prior to screening and randomization.
* Known hypersensitivity to any of the ingredients or excipients of the study drug.
* Exposure to another investigational drug within 4 weeks prior to screening.
* Treatment with intravenous antibiotics within 3 weeks prior to screening.
* History of solid organ or hematological transplantation.
* Ongoing immunosuppressive therapy (other than corticosteroids).
* Positive hepatitis B surface antigen, hepatitis C antibody test or human immunodeficiency virus (HIV) test.
* Known portal hypertension.
* Pregnancy or breast-feeding.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline (Day 1) up to end of study (Week 196)
measure: Number of Participants With Clinically Significant Laboratory Abnormalities
timeFrame: Baseline (Day 1) up to end of study (Week 196)
Secondary outcomes:
measure: Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at the End of Treatment (Week 192), as Assessed by Spirometry
timeFrame: Baseline, Week 192
measure: Percentage of Participants With Pulmonary Exacerbation, As Assessed by Modified Fuchs Criteria
timeFrame: Baseline up to Week 192
measure: Percentage of Participants With Pulmonary Exacerbation, As Assessed by Expanded Fuchs' Criteria
timeFrame: Baseline up to Week 192
measure: Percentage of Participants With Pulmonary Exacerbation, As Assessed by Classic Fuchs' Criteria
timeFrame: Baseline up to Week 192
measure: Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters at Final Visit (Week 196)
timeFrame: Baseline, Week 196
measure: Change From Baseline in Heart Rate at Final Visit (Week 196), as Assessed by 12-Lead ECG
timeFrame: Baseline, Week 196
measure: Change From Baseline in Vital Signs at Final Visit (Week 196)
timeFrame: Baseline, Week 196
Other outcomes:
measure: Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at the End of Treatment (Week 192), as Assessed by Spirometry
timeFrame: Baseline, Week 192
measure: Change From Baseline in Percent Predicted Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) at the End of Treatment (Week 192), as Assessed by Spirometry
timeFrame: Baseline, Week 192
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: Aurora
country: United States
facility: Denver Children's Hospital
state: Colorado
city: Chicago
country: United States
facility: Children's Hospital Chicago
state: Illinois
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: Cleveland
country: United States
facility: Rainbow Babies & Children's Hospital
state: Ohio
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: Paris
country: France
facility: Hôpital Necker - Enfants Malades
city: Toulouse
country: France
facility: Hôpital des Enfants
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: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Stockholm
country: Sweden
facility: Karolinska University Hospital, Huddinge
Study officials:
affiliation: PTC Therapeutics, Inc.
name: Joseph McIntosh, MD
role: STUDY_DIRECTOR
References: