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Study of Ataluren (PTC124) in Cystic Fibrosis

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ClinicalTrials.gov Identifier: NCT02107859
Recruitment Status : Terminated (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.)
First Posted : April 8, 2014
Results First Posted : March 25, 2020
Last Update Posted : March 25, 2020
Sponsor:
Information provided by (Responsible Party):
PTC Therapeutics

Tracking Information
First Submitted Date  ICMJE April 4, 2014
First Posted Date  ICMJE April 8, 2014
Results First Submitted Date  ICMJE March 11, 2020
Results First Posted Date  ICMJE March 25, 2020
Last Update Posted Date March 25, 2020
Actual Study Start Date  ICMJE May 23, 2014
Actual Primary Completion Date June 5, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 11, 2020)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 7, 2014)
Adverse events and laboratory abnormalities [ Time Frame: 48 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2020)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: April 7, 2014)
  • Forced expiratory volume in 1 second (FEV1) [ Time Frame: 48 weeks ]
  • Pulmonary exacerbation rate [ Time Frame: 48 weeks ]
  • 12 Lead ECG [ Time Frame: 48 Weeks ]
  • Vital Signs [ Time Frame: 48 Weeks ]
  • Physical Examination [ Time Frame: 48 Weeks ]
Current Other Pre-specified Outcome Measures
 (submitted: March 11, 2020)
  • 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.
  • 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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Ataluren (PTC124) in Cystic Fibrosis
Official Title  ICMJE An Open-Label Safety and Efficacy Study for Patients With Nonsense Mutation Cystic Fibrosis Previously Treated With Ataluren (PTC124)
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cystic Fibrosis
Intervention  ICMJE Drug: Ataluren
Ataluren will be administered per dose and schedule specified in the arm.
Other Name: PTC124
Study Arms  ICMJE 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.
Intervention: Drug: Ataluren
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 30, 2017)
61
Original Estimated Enrollment  ICMJE
 (submitted: April 7, 2014)
80
Actual Study Completion Date  ICMJE June 5, 2017
Actual Primary Completion Date June 5, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Israel,   Italy,   Spain,   Sweden,   United States
Removed Location Countries Germany
 
Administrative Information
NCT Number  ICMJE NCT02107859
Other Study ID Numbers  ICMJE PTC124-GD-023-CF
2013-005449-35 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party PTC Therapeutics
Study Sponsor  ICMJE PTC Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Joseph McIntosh, MD PTC Therapeutics, Inc.
PRS Account PTC Therapeutics
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP