Extension Study of Ataluren in Participants With Nonsense Mutation Cystic Fibrosis
- Registration Number
- NCT02456103
- Lead Sponsor
- PTC Therapeutics
- Brief Summary
This is an open-label extension study for participants who completed a Phase 3, placebo-controlled study of ataluren in participants with nonsense mutation cystic fibrosis (nmCF) not receiving chronic inhaled aminoglycosides.
- Detailed Description
The primary objective of this Phase 3 extension study will be to obtain long-term safety data to augment the overall safety database. The secondary objectives will be to augment the efficacy data collected in the double-blind study (PTC124-GD-021-CF; NCT02139306).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 246
- Completion of study treatment (placebo or active) in the previous Phase 3, double-blind study protocol (Protocol PTC124-GD-021-CF)
- Evidence of signed and dated informed consent/assent document(s) indicating that the participant (and/or the participant's parent/legal guardian) has been informed of all pertinent aspects of the trial.
- Known hypersensitivity to any of the ingredients or excipients of the study drug.
- Ongoing participation in any other therapeutic clinical trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ataluren Ataluren Participants will be administered ataluren orally at a dose of 10 milligrams/grams (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
- Primary Outcome Measures
Name Time Method Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Serum Biochemistry, Hematology, and Urinalysis) Parameter Baseline up to Week 100 Clinical laboratory results considered clinically meaningful were determined by Investigator. Serum biochemistry parameters: sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, magnesium, calcium, phosphorus, uric acid, glucose, total protein, albumin, globulin, bilirubin, creatine kinase, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, and cystatin C. Hematology parameters: white blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, red cell count with morphology, and platelet count. Urinalysis parameters: pH, specific gravity, glucose, ketones, blood, protein, creatinine, urobilinogen, bilirubin, nitrite, and leukocyte esterase. A summary of all SAEs/nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Baseline up to Week 100 TEAE: any untoward medical occurrence or undesirable event that begins or worsens following administration of study drug, whether or not considered related to study drug by Investigator. Serious adverse event (SAE): an adverse event (AE) resulting in any of following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying) or persistent or significant disability/incapacity. Except for cystic fibrosis (CF) pulmonary exacerbations, an event wasn't reported as an SAE, if event was exclusively a relapse or an expected change or progression of baseline CF. AEs included both SAEs and nonserious AEs. AEs classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 and coded using Medical Dictionary for Regulatory Activities. A summary of SAEs and all nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.
- Secondary Outcome Measures
Name Time Method Rate of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Over 48 Weeks Baseline up to Week 48 A modified Fuchs' exacerbation was defined as an event requiring treatment with or without intravenous antibiotics for any 4 of the following 12 symptoms: 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. The 48-week rate = (the total number of events/ treatment duration by week)\*48.
Change From Baseline in Percent-Predicted Forced Expiratory Volume in 1 Second (FEV1) as Measured by Spirometry at Week 24 Baseline, Week 24 Pulmonary function of percent-predicted FEV1 was measured using a spirometer. FEV1 is the volume of air that can forcibly be blown out in 1 second. Each percent-predicted FEV1 was based gender, age, and the height value obtained at the same study visit. The percentage of change in percent-predicted of FEV1 was calculated as follows: (percent-predicted FEV1 - Baseline percent-predicted FEV1/Baseline percent-predicted FEV1)\*100.
Change From Baseline in Percent-Predicted of Forced Vital Capacity (FVC) as Measured by Spirometry at Week 24 Baseline, Week 24 Pulmonary function of FVC was measured using a spirometer. FVC is the volume of air that can forcibly be blown out. Each percent-predicted FVC was based gender, age, and the height value obtained at the same study visit. The percentage of change in percent-predicted of FVC was calculated as follows: (percent-predicted FVC - Baseline percent-predicted FVC/Baseline percent-predicted FVC)\*100.
Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) as Measured by Spirometry at Week 24 Baseline, Week 24 Pulmonary function of FEF25-75 was measured using a spirometer. FEF25-75 is the forced expiratory flow between 25% and 75% of vital capacity. Each percent-predicted FEF25-75 was based gender, age, and the height value obtained at the same study visit. The percentage of change in percent-predicted of FEF25-75 was calculated as follows: (percent-predicted FEF25-75 - Baseline percent-predicted FEF25-75/Baseline percent-predicted FEF25-75)\*100.
Trial Locations
- Locations (70)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Miller Children's Hospital Long Beach
🇺🇸Long Beach, California, United States
Children's Hospital and Research Center at Oakland
🇺🇸Oakland, California, United States
Stanford University-Children's Hospital
🇺🇸Palo Alto, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Nemours Children's Clinic
🇺🇸Jacksonville, Florida, United States
Miami Children's Hospital
🇺🇸Miami, Florida, United States
All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Children's Hospital Boston
🇺🇸Boston, Massachusetts, United States
Beth Israel Medical Center
🇺🇸New York, New York, United States
New York University Langone Medical Center
🇺🇸New York, New York, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Drexel University College of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
University of Texas Health Science Center
🇺🇸Tyler, Texas, United States
Childrens Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Hospital Universitario Austral
🇦🇷Buenos Aires, Argentina
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
Hospital de Ninos Ricardo Gutierrez
🇦🇷Buenos Aires, Argentina
Princess Margaret Hospital
🇦🇺Perth, Australia
Prince Charles Hospital
🇦🇺Chermside, Australia
University Hospital Brussels
🇧🇪Brussels, Belgium
Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul
🇧🇷Porto Alegre, Brazil
University Mulitiprofile Hospital for Active Treatment Sveti Georgi EAD
🇧🇬Plovdiv, Bulgaria
University Multiprofile Hospital for Active Treatment Aleksandrovska EAD
🇧🇬Sofia, Bulgaria
Clinical Research Institute of Montreal
🇨🇦Montreal, Canada
University of Toronto Hospital for Sick Children
🇨🇦Toronto, Canada
British Columbia Children's Hospital
🇨🇦Vancouver, Canada
Hoptial Arnaud de Villeneuve
🇫🇷Montpellier, France
Hopital Necker - Enfants Malades
🇫🇷Paris, France
Centre Hospitalier Regional Sud Reunion
🇫🇷Saint-Pierre, France
St. Josef Hospital GmbH
🇩🇪Bochum, Germany
Charite-Universitatsmedizin Berlin
🇩🇪Berlin, Germany
University of Cologne Children's Hospital
🇩🇪Cologne, Germany
Christiane Herzog CF-Zentrum
🇩🇪Frankfurt am Main, Germany
Dr. Von Haunersches Kinderspital
🇩🇪Munchen, Germany
LMU Klinikum der Universitat Muchen
🇩🇪Munich, Germany
Ippokratio General Hospital Of Thessaloniki
🇬🇷Thessaloniki, Greece
Universitatsklinikum Jena
🇩🇪Jena, Germany
Szpital Dzieciecy Polanki im Macieja Plazynskiego w Gdansku
🇵🇱Gdansk, Poland
Institute of Mother and Child
🇵🇱Warsaw, Poland
Hagaziekenhuis
🇳🇱s-Gravenweg, Zuid-Holland, Netherlands
Radboud University
🇳🇱Nijmegen, Netherlands
Hospital San Juan
🇪🇸Esplugues De Llobregat, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital University
🇪🇸Barcelona, Spain
Hospital Regional Universitario de Malaga
🇪🇸Malaga, Spain
Hospital de Sabadell, Consorci Sanitari Parc Tauli
🇪🇸Sabadell, Spain
St James University Hospital
🇬🇧Leeds, United Kingdom
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Azienda Ospedaliero Universitaria Ospedall Riuniti di Acona-Umberto I G.M. Lancisi G. Salesi
🇮🇹Ancona, Italy
Azienda Ospedaliera A Meyer
🇮🇹Firenze, Italy
Lombardia Cystic Fibrosis Center
🇮🇹Milan, Italy
Azienda Policlinico Umberto I
🇮🇹Rome, Italy
Ospedale Pediatrico Bambino Gesu
🇮🇹Rome, Italy
Azienda Ospedaliera di Verona
🇮🇹Verona, Italy
Centre de Perharidy
🇫🇷Roscoff, France
Ann and Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
University Hospital Leuven
🇧🇪Leuven, Belgium
Hadassah University Hospital
🇮🇱Jerusalem, Israel
Hopital Universitaire des Enfants Reine Fabiola
🇧🇪Brussels, Belgium
Meyer Children's Hospital
🇮🇱Haifa, Israel
University of Miami
🇺🇸Miami, Florida, United States
Royal Brompton Hospital
🇬🇧London, United Kingdom