Back to resultsStudy of Ataluren (PTC124) in 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 focused on measuring Cystic fibrosis, Nonsense mutation, Premature stop codon, PTC124, Ataluren
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.
Sites / Locations
- University of Alabama-Birmingham
- Miller Children's Hospital Long Beach
- Denver Children's Hospital
- Children's Hospital Chicago
- Children's Hospital Boston
- Beth Israel Medical Center
- Rainbow Babies & Children's Hospital
- Hôpital Universitaire des Enfants Reine Fabiola
- University Hospital Brussels
- University Hospital Leuven
- Hôpital Necker - Enfants Malades
- Hôpital des Enfants
- Hadassah University Hospital - Mount Scopus
- Università La Sapienza
- Azienda Ospedaliera di Verona
- Hospital Universitario La Paz
- Karolinska University Hospital, Huddinge
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ataluren
Arm Description
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.
Outcomes
Primary Outcome Measures
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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.
Number of Participants With Clinically Significant Laboratory Abnormalities
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.
Secondary Outcome Measures
Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at the End of Treatment (Week 192), as Assessed by Spirometry
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.
Percentage of Participants With Pulmonary Exacerbation, As Assessed by Modified Fuchs Criteria
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.
Percentage of Participants With Pulmonary Exacerbation, As Assessed by Expanded Fuchs' Criteria
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.
Percentage of Participants With Pulmonary Exacerbation, As Assessed by Classic Fuchs' Criteria
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.
Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters at Final Visit (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.
Change From Baseline in Heart Rate at Final Visit (Week 196), as Assessed by 12-Lead ECG
Heart rate was measured using 12-lead ECG.
Change From Baseline in Vital Signs at Final Visit (Week 196)
Vital Signs included systolic blood pressure (SBP) and diastolic blood pressure (DBP).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02107859
Brief Title
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
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Terminated
Why Stopped
Based on the results of study PTC124-GD-021-CF (NCT02139306), clinical development of ataluren in cystic fibrosis was discontinued and this study was closed.
Study Start Date
May 23, 2014 (Actual)
Primary Completion Date
June 5, 2017 (Actual)
Study Completion Date
June 5, 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
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
Cystic fibrosis, Nonsense mutation, Premature stop codon, PTC124, Ataluren
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
61 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ataluren
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ataluren
Other Intervention Name(s)
PTC124
Intervention Description
Ataluren will be administered per dose and schedule specified in the arm.
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description
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.
Time Frame
Baseline (Day 1) up to end of study (Week 196)
Title
Number of Participants With Clinically Significant Laboratory Abnormalities
Description
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.
Time Frame
Baseline (Day 1) up to end of study (Week 196)
Secondary Outcome Measure Information:
Title
Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at the End of Treatment (Week 192), as Assessed by Spirometry
Description
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.
Time Frame
Baseline, Week 192
Title
Percentage of Participants With Pulmonary Exacerbation, As Assessed by Modified Fuchs Criteria
Description
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.
Time Frame
Baseline up to Week 192
Title
Percentage of Participants With Pulmonary Exacerbation, As Assessed by Expanded Fuchs' Criteria
Description
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.
Time Frame
Baseline up to Week 192
Title
Percentage of Participants With Pulmonary Exacerbation, As Assessed by Classic Fuchs' Criteria
Description
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.
Time Frame
Baseline up to Week 192
Title
Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters at Final Visit (Week 196)
Description
ECG parameters included RR duration, PR duration, QRS duration, QT duration, QTCB (Bazett's correction formula) duration, QTCF (Fridericia's correction formula) duration.
Time Frame
Baseline, Week 196
Title
Change From Baseline in Heart Rate at Final Visit (Week 196), as Assessed by 12-Lead ECG
Description
Heart rate was measured using 12-lead ECG.
Time Frame
Baseline, Week 196
Title
Change From Baseline in Vital Signs at Final Visit (Week 196)
Description
Vital Signs included systolic blood pressure (SBP) and diastolic blood pressure (DBP).
Time Frame
Baseline, Week 196
Other Pre-specified Outcome Measures:
Title
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at the End of Treatment (Week 192), as Assessed by Spirometry
Description
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.
Time Frame
Baseline, Week 192
Title
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
Description
FEF25-75 is the forced expiratory flow between 25 and 75% of vital capacity.
Time Frame
Baseline, Week 192
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph McIntosh, MD
Organizational Affiliation
PTC Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama-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
Denver Children's Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Children's Hospital Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
Children's Hospital Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beth Israel Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Rainbow Babies & Children's Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Hôpital Universitaire des Enfants Reine Fabiola
City
Brussels
Country
Belgium
Facility Name
University Hospital Brussels
City
Brussels
Country
Belgium
Facility Name
University Hospital Leuven
City
Leuven
Country
Belgium
Facility Name
Hôpital Necker - Enfants Malades
City
Paris
Country
France
Facility Name
Hôpital des Enfants
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Hadassah University Hospital - Mount Scopus
City
Jerusalem
ZIP/Postal Code
91240
Country
Israel
Facility Name
Università La Sapienza
City
Roma
Country
Italy
Facility Name
Azienda Ospedaliera di Verona
City
Verona
Country
Italy
Facility Name
Hospital Universitario La Paz
City
Madrid
Country
Spain
Facility Name
Karolinska University Hospital, Huddinge
City
Stockholm
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.ptcbio.com
Description
PTC Therapeutics, Inc. website
Learn more about this trial
Study of Ataluren (PTC124) in Cystic Fibrosis
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