Back to resultsExtension Study of Ataluren in Participants With Nonsense Mutation Cystic Fibrosis
Primary Purpose
Cystic Fibrosis
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ataluren
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- Known hypersensitivity to any of the ingredients or excipients of the study drug.
- Ongoing participation in any other therapeutic clinical trial.
Sites / Locations
- University of Alabama at Birmingham
- Miller Children's Hospital Long Beach
- Children's Hospital Los Angeles
- Children's Hospital and Research Center at Oakland
- Stanford University-Children's Hospital
- Children's Hospital Colorado
- Nemours Children's Clinic
- University of Miami
- Miami Children's Hospital
- All Children's Hospital
- Ann and Robert H. Lurie Children's Hospital of Chicago
- Indiana University
- Children's Hospital Boston
- Washington University
- Morristown Medical Center
- Beth Israel Medical Center
- New York University Langone Medical Center
- Columbia University Medical Center
- University of Cincinnati
- Penn State Milton S. Hershey Medical Center
- Drexel University College of Medicine
- Texas Children's Hospital
- University of Texas Health Science Center
- Childrens Hospital of Wisconsin
- Hospital de Ninos Ricardo Gutierrez
- Hospital Universitario Austral
- Royal Adelaide Hospital
- Prince Charles Hospital
- Princess Margaret Hospital
- University Hospital Brussels
- Hopital Universitaire des Enfants Reine Fabiola
- University Hospital Leuven
- Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul
- University Mulitiprofile Hospital for Active Treatment Sveti Georgi EAD
- University Multiprofile Hospital for Active Treatment Aleksandrovska EAD
- Clinical Research Institute of Montreal
- University of Toronto Hospital for Sick Children
- British Columbia Children's Hospital
- Hoptial Arnaud de Villeneuve
- Hopital Necker - Enfants Malades
- Centre de Perharidy
- Centre Hospitalier Regional Sud Reunion
- Charite-Universitatsmedizin Berlin
- St. Josef Hospital GmbH
- University of Cologne Children's Hospital
- Christiane Herzog CF-Zentrum
- Universitatsklinikum Jena
- Dr. Von Haunersches Kinderspital
- LMU Klinikum der Universitat Muchen
- Ippokratio General Hospital Of Thessaloniki
- Meyer Children's Hospital
- Hadassah University Hospital
- Azienda Ospedaliero Universitaria Ospedall Riuniti di Acona-Umberto I G.M. Lancisi G. Salesi
- Azienda Ospedaliera A Meyer
- Lombardia Cystic Fibrosis Center
- Azienda Policlinico Umberto I
- Ospedale Pediatrico Bambino Gesu
- Azienda Ospedaliera di Verona
- Hagaziekenhuis
- Radboud University
- Szpital Dzieciecy Polanki im Macieja Plazynskiego w Gdansku
- Institute of Mother and Child
- Hospital Universitario Vall d'Hebron
- Hospital University
- Hospital San Juan
- Hospital Regional Universitario de Malaga
- Hospital de Sabadell, Consorci Sanitari Parc Tauli
- Hospital Universitario Virgen del Rocio
- St James University Hospital
- Royal Brompton Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ataluren
Arm Description
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.
Outcomes
Primary Outcome Measures
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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.
Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Serum Biochemistry, Hematology, and Urinalysis) Parameter
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.
Secondary Outcome Measures
Change From Baseline in Percent-Predicted Forced Expiratory Volume in 1 Second (FEV1) as Measured by Spirometry at 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
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
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.
Rate of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Over 48 Weeks
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02456103
Brief Title
Extension Study of Ataluren in Participants With Nonsense Mutation Cystic Fibrosis
Official Title
Phase 3 Extension Study of Ataluren (PTC124) in Patients With Nonsense Mutation Cystic Fibrosis
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Terminated
Why Stopped
Cystic Fibrosis (CF) data from the double-blind CF Study PTC124-GD-021-CF did not meet endpoints.
Study Start Date
August 31, 2015 (Actual)
Primary Completion Date
June 2, 2017 (Actual)
Study Completion Date
June 2, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PTC Therapeutics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
246 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ataluren
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ataluren
Other Intervention Name(s)
PTC124, Translarna
Intervention Description
Ataluren will be provided as a vanilla-flavored powder to be mixed with water or milk.
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Description
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.
Time Frame
Baseline up to Week 100
Title
Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Serum Biochemistry, Hematology, and Urinalysis) Parameter
Description
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.
Time Frame
Baseline up to Week 100
Secondary Outcome Measure Information:
Title
Change From Baseline in Percent-Predicted Forced Expiratory Volume in 1 Second (FEV1) as Measured by Spirometry at Week 24
Description
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.
Time Frame
Baseline, Week 24
Title
Change From Baseline in Percent-Predicted of Forced Vital Capacity (FVC) as Measured by Spirometry at Week 24
Description
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.
Time Frame
Baseline, Week 24
Title
Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) as Measured by Spirometry at Week 24
Description
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.
Time Frame
Baseline, Week 24
Title
Rate of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Over 48 Weeks
Description
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.
Time Frame
Baseline up to Week 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
Known hypersensitivity to any of the ingredients or excipients of the study drug.
Ongoing participation in any other therapeutic clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph McIntosh, MD
Organizational Affiliation
PTC Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Miller Children's Hospital Long Beach
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Children's Hospital and Research Center at Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Stanford University-Children's Hospital
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Nemours Children's Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Miami Children's Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
All Children's Hospital
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Ann and Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Children's Hospital Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Morristown Medical Center
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07960
Country
United States
Facility Name
Beth Israel Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10011
Country
United States
Facility Name
New York University Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45221
Country
United States
Facility Name
Penn State Milton S. Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Drexel University College of Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19129
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77094
Country
United States
Facility Name
University of Texas Health Science Center
City
Tyler
State/Province
Texas
ZIP/Postal Code
75708
Country
United States
Facility Name
Childrens Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Hospital de Ninos Ricardo Gutierrez
City
Buenos Aires
ZIP/Postal Code
1330
Country
Argentina
Facility Name
Hospital Universitario Austral
City
Buenos Aires
Country
Argentina
Facility Name
Royal Adelaide Hospital
City
Adelaide
ZIP/Postal Code
5000
Country
Australia
Facility Name
Prince Charles Hospital
City
Chermside
ZIP/Postal Code
4032
Country
Australia
Facility Name
Princess Margaret Hospital
City
Perth
ZIP/Postal Code
6840
Country
Australia
Facility Name
University Hospital Brussels
City
Brussels
ZIP/Postal Code
1090
Country
Belgium
Facility Name
Hopital Universitaire des Enfants Reine Fabiola
City
Brussels
ZIP/Postal Code
15
Country
Belgium
Facility Name
University Hospital Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul
City
Porto Alegre
Country
Brazil
Facility Name
University Mulitiprofile Hospital for Active Treatment Sveti Georgi EAD
City
Plovdiv
Country
Bulgaria
Facility Name
University Multiprofile Hospital for Active Treatment Aleksandrovska EAD
City
Sofia
Country
Bulgaria
Facility Name
Clinical Research Institute of Montreal
City
Montreal
ZIP/Postal Code
H2W 1R7
Country
Canada
Facility Name
University of Toronto Hospital for Sick Children
City
Toronto
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
British Columbia Children's Hospital
City
Vancouver
ZIP/Postal Code
V6H 3V4
Country
Canada
Facility Name
Hoptial Arnaud de Villeneuve
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Hopital Necker - Enfants Malades
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Centre de Perharidy
City
Roscoff
ZIP/Postal Code
29684
Country
France
Facility Name
Centre Hospitalier Regional Sud Reunion
City
Saint-Pierre
ZIP/Postal Code
97448
Country
France
Facility Name
Charite-Universitatsmedizin Berlin
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
St. Josef Hospital GmbH
City
Bochum
ZIP/Postal Code
44791
Country
Germany
Facility Name
University of Cologne Children's Hospital
City
Cologne
ZIP/Postal Code
50937
Country
Germany
Facility Name
Christiane Herzog CF-Zentrum
City
Frankfurt am Main
ZIP/Postal Code
60590
Country
Germany
Facility Name
Universitatsklinikum Jena
City
Jena
ZIP/Postal Code
1
Country
Germany
Facility Name
Dr. Von Haunersches Kinderspital
City
Munchen
ZIP/Postal Code
80337
Country
Germany
Facility Name
LMU Klinikum der Universitat Muchen
City
Munich
ZIP/Postal Code
80539
Country
Germany
Facility Name
Ippokratio General Hospital Of Thessaloniki
City
Thessaloniki
ZIP/Postal Code
541
Country
Greece
Facility Name
Meyer Children's Hospital
City
Haifa
ZIP/Postal Code
31096
Country
Israel
Facility Name
Hadassah University Hospital
City
Jerusalem
ZIP/Postal Code
91240
Country
Israel
Facility Name
Azienda Ospedaliero Universitaria Ospedall Riuniti di Acona-Umberto I G.M. Lancisi G. Salesi
City
Ancona
ZIP/Postal Code
71
Country
Italy
Facility Name
Azienda Ospedaliera A Meyer
City
Firenze
ZIP/Postal Code
50139
Country
Italy
Facility Name
Lombardia Cystic Fibrosis Center
City
Milan
ZIP/Postal Code
20122
Country
Italy
Facility Name
Azienda Policlinico Umberto I
City
Rome
ZIP/Postal Code
00161
Country
Italy
Facility Name
Ospedale Pediatrico Bambino Gesu
City
Rome
ZIP/Postal Code
4
Country
Italy
Facility Name
Azienda Ospedaliera di Verona
City
Verona
Country
Italy
Facility Name
Hagaziekenhuis
City
s-Gravenweg
State/Province
Zuid-Holland
ZIP/Postal Code
2545 CH
Country
Netherlands
Facility Name
Radboud University
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
Facility Name
Szpital Dzieciecy Polanki im Macieja Plazynskiego w Gdansku
City
Gdansk
Country
Poland
Facility Name
Institute of Mother and Child
City
Warsaw
ZIP/Postal Code
01-211
Country
Poland
Facility Name
Hospital Universitario Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital University
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital San Juan
City
Esplugues De Llobregat
ZIP/Postal Code
08950
Country
Spain
Facility Name
Hospital Regional Universitario de Malaga
City
Malaga
ZIP/Postal Code
29001
Country
Spain
Facility Name
Hospital de Sabadell, Consorci Sanitari Parc Tauli
City
Sabadell
ZIP/Postal Code
08208
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
St James University Hospital
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Royal Brompton Hospital
City
London
ZIP/Postal Code
SW3 6NP
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Extension Study of Ataluren in Participants With Nonsense Mutation Cystic Fibrosis
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