- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02107859
Study of Ataluren (PTC124) in Cystic Fibrosis
March 11, 2020 updated by: PTC Therapeutics
An Open-Label Safety and Efficacy Study for Patients With Nonsense Mutation Cystic Fibrosis Previously Treated With Ataluren (PTC124)
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).
Study Overview
Study Type
Interventional
Enrollment (Actual)
61
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Brussels, Belgium
- University Hospital Brussels
-
Brussels, Belgium
- Hôpital Universitaire des Enfants Reine Fabiola
-
Leuven, Belgium
- University Hospital Leuven
-
-
-
-
-
Paris, France
- Hôpital Necker - Enfants Malades
-
Toulouse, France, 31059
- Hôpital des Enfants
-
-
-
-
-
Jerusalem, Israel, 91240
- Hadassah University Hospital - Mount Scopus
-
-
-
-
-
Roma, Italy
- Università La Sapienza
-
Verona, Italy
- Azienda Ospedaliera di Verona
-
-
-
-
-
Madrid, Spain
- Hospital Universitario La Paz
-
-
-
-
-
Stockholm, Sweden
- Karolinska University Hospital, Huddinge
-
-
-
-
Alabama
-
Birmingham, Alabama, United States, 35233
- University of Alabama-Birmingham
-
-
California
-
Long Beach, California, United States, 90806
- Miller Children's Hospital Long Beach
-
-
Colorado
-
Aurora, Colorado, United States, 80045
- Denver Children's Hospital
-
-
Illinois
-
Chicago, Illinois, United States, 60614
- Children's Hospital Chicago
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02115
- Children's Hospital Boston
-
-
New York
-
New York, New York, United States, 10003
- Beth Israel Medical Center
-
-
Ohio
-
Cleveland, Ohio, United States, 44106
- Rainbow Babies & Children's Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
6 years and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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 192 weeks.
|
Ataluren will be administered per dose and schedule specified in the arm.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Baseline (Day 1) up to end of study (Week 196)
|
AE: any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Severity of an AE was classified as: mild (does not interfere with usual function), moderate (interferes to some extent with usual function), severe (interferes significantly with usual function), life threatening (results in potential threat to life), and fatal AEs.
Drug-related AEs: AEs with a possible or probable relationship to study drug.
Serious AEs: 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: AE that occurred or worsened from first dose of study drug to 4 weeks after last dose of study drug.
A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
|
Baseline (Day 1) up to end of study (Week 196)
|
Number of Participants With Clinically Significant Laboratory Abnormalities
Time Frame: Baseline (Day 1) up to end of study (Week 196)
|
Laboratory parameters tests included hematology, biochemistry assay (hepatic, renal, and serum electrolyte values), adrenal assays, and urinalysis.
Clinical significance was defined as per investigator's judgement.
|
Baseline (Day 1) up to end of study (Week 196)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at the End of Treatment (Week 192), as Assessed by Spirometry
Time Frame: Baseline, Week 192
|
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Percent of predicted FEV1 = (observed value)/(predicted value) * 100%.
Change from baseline in percent predicted FEV1 at the end of treatment was reported.
|
Baseline, Week 192
|
Percentage of Participants With Pulmonary Exacerbation, As Assessed by Modified Fuchs Criteria
Time Frame: Baseline up to Week 192
|
The modified Fuchs' criteria defined exacerbation as the presence of at least 4 of the following 12 Fuchs' signs and symptoms without the requirement for treatment with antibiotics: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; fatigue; temperature greater than (>) 38 degrees celsius (°C); anorexia; sinus pain; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent or more from a previously recorded value; or radiographic changes indicative of pulmonary function.
|
Baseline up to Week 192
|
Percentage of Participants With Pulmonary Exacerbation, As Assessed by Expanded Fuchs' Criteria
Time Frame: Baseline up to Week 192
|
The expanded Fuchs' criteria defined exacerbation as the presence of at least 4 of the following 12 Fuchs' signs and symptoms requiring any form of antibiotic treatment (inhaled, oral, or intravenous): change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; fatigue; temperature >38°C; anorexia; sinus pain; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent or more from a previously recorded value; or radiographic changes indicative of pulmonary function.
|
Baseline up to Week 192
|
Percentage of Participants With Pulmonary Exacerbation, As Assessed by Classic Fuchs' Criteria
Time Frame: Baseline up to Week 192
|
The Classic Fuchs' criteria defined exacerbation as the presence of at least 4 of the following 12 Fuchs' signs and symptoms requiring treatment with parenteral antibiotics: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; fatigue; temperature >38°C; anorexia; sinus pain; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent or more from a previously recorded value; or radiographic changes indicative of pulmonary function.
|
Baseline up to Week 192
|
Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters at Final Visit (Week 196)
Time Frame: Baseline, Week 196
|
ECG parameters included RR duration, PR duration, QRS duration, QT duration, QTCB (Bazett's correction formula) duration, QTCF (Fridericia's correction formula) duration.
|
Baseline, Week 196
|
Change From Baseline in Heart Rate at Final Visit (Week 196), as Assessed by 12-Lead ECG
Time Frame: Baseline, Week 196
|
Heart rate was measured using 12-lead ECG.
|
Baseline, Week 196
|
Change From Baseline in Vital Signs at Final Visit (Week 196)
Time Frame: Baseline, Week 196
|
Vital Signs included systolic blood pressure (SBP) and diastolic blood pressure (DBP).
|
Baseline, Week 196
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at the End of Treatment (Week 192), as Assessed by Spirometry
Time Frame: Baseline, Week 192
|
FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position.
Percent of predicted FVC = (observed value)/(predicted value) * 100%.
Change from baseline in percent predicted FVC at the end of treatment was reported.
|
Baseline, Week 192
|
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
Time Frame: Baseline, Week 192
|
FEF25-75 is the forced expiratory flow between 25 and 75% of vital capacity.
|
Baseline, Week 192
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Joseph McIntosh, MD, PTC Therapeutics, Inc.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 23, 2014
Primary Completion (Actual)
June 5, 2017
Study Completion (Actual)
June 5, 2017
Study Registration Dates
First Submitted
April 4, 2014
First Submitted That Met QC Criteria
April 7, 2014
First Posted (Estimate)
April 8, 2014
Study Record Updates
Last Update Posted (Actual)
March 25, 2020
Last Update Submitted That Met QC Criteria
March 11, 2020
Last Verified
March 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PTC124-GD-023-CF
- 2013-005449-35 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cystic Fibrosis
-
Hospital de Clinicas de Porto AlegreUnknownCystic Fibrosis | Cystic Fibrosis Pulmonary Exacerbation | Cystic Fibrosis in Children | Cystic Fibrosis With ExacerbationBrazil
-
University of Colorado, DenverCystic Fibrosis FoundationTerminatedCystic Fibrosis-related Diabetes | Cystic Fibrosis Pulmonary Exacerbation | Cystic Fibrosis in ChildrenUnited States
-
Royal College of Surgeons, IrelandThe Hospital for Sick Children; Imperial College London; Erasmus Medical Center; University College Dublin and other collaboratorsActive, not recruitingCystic Fibrosis | Adherence, Medication | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis in Children | Cystic Fibrosis Liver DiseaseUnited Kingdom, Ireland
-
Herlev and Gentofte HospitalCopenhagen University Hospital, DenmarkActive, not recruitingMyocardial Infarction | Heart Diseases | Heart Failure | Stroke | Cystic Fibrosis | Heart Failure, Diastolic | Heart Failure, Systolic | Left Ventricular Dysfunction | Cystic Fibrosis-related Diabetes | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis of Pancreas | Cystic Fibrosis, Pulmonary | Cystic...Denmark
-
The Hospital for Sick ChildrenCanadian Cystic Fibrosis FoundationActive, not recruitingCystic Fibrosis | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis in ChildrenCanada
-
Arrowhead PharmaceuticalsTerminatedCystic Fibrosis, PulmonaryAustralia, New Zealand
-
AzurRx SASCompletedCystic Fibrosis | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis of PancreasTurkey, Hungary
-
Dartmouth-Hitchcock Medical CenterTrustees of Dartmouth CollegeWithdrawnCystic Fibrosis-related Diabetes | Cystic Fibrosis Liver Disease | CF - Cystic FibrosisUnited States
-
University Hospital, BordeauxCompleted
-
University of PortsmouthUniversity Hospital Southampton NHS Foundation Trust; Loughborough University; Queen Alexandra HospitalTerminated
Clinical Trials on Ataluren
-
PTC TherapeuticsCystic Fibrosis FoundationCompletedCystic FibrosisUnited States, France, Belgium, Spain, Canada, Germany, Israel, Italy, Netherlands, Sweden, United Kingdom
-
PTC TherapeuticsTerminatedNervous System Diseases | Genetic Diseases, Inborn | Genetic Diseases, X-Linked | Musculoskeletal Diseases | Muscular Diseases | Neuromuscular Diseases | Muscular Dystrophies | Muscular Disorders, Atrophic | Muscular Dystrophy, DuchenneUnited States, Spain, Korea, Republic of, Belgium, France, Canada, Australia, United Kingdom, Israel, Italy, Germany, Brazil, Bulgaria, Chile, Czechia, Poland, Sweden, Switzerland, Turkey
-
PTC TherapeuticsGenzyme, a Sanofi CompanyTerminatedAmino Acid Metabolism, Inborn ErrorsFrance, United Kingdom, Italy, Belgium, Germany, Switzerland
-
PTC TherapeuticsCompletedDuchenne Muscular DystrophyUnited States
-
PTC TherapeuticsCompletedDuchenne Muscular Dystrophy | Becker Muscular DystrophyUnited States, Germany, Spain, Sweden, Canada, Italy, Australia, Belgium, France, Israel, United Kingdom
-
PTC TherapeuticsEnrolling by invitationDuchenne Muscular DystrophyUnited States, Canada
-
PTC TherapeuticsCompletedDuchenne Muscular DystrophyUnited States
-
PTC TherapeuticsGenzyme, a Sanofi CompanyTerminatedDuchenne Muscular DystrophyUnited States
-
PTC TherapeuticsGenzyme, a Sanofi CompanyTerminatedDuchenne Muscular Dystrophy | Becker Muscular DystrophyUnited States, Belgium, Australia, Canada, France, Germany, Israel, Italy, Spain, Sweden, United Kingdom
-
PTC TherapeuticsCompletedNonsene Mutation Duchenne Muscular DystrophyUnited States