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Extension Study of Ataluren in Participants With Nonsense Mutation Cystic Fibrosis

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ClinicalTrials.gov Identifier: NCT02456103
Recruitment Status : Terminated (Cystic Fibrosis (CF) data from the double-blind CF Study PTC124-GD-021-CF did not meet endpoints.)
First Posted : May 28, 2015
Results First Posted : April 15, 2020
Last Update Posted : April 27, 2020
Sponsor:
Information provided by (Responsible Party):
PTC Therapeutics

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Intervention Drug: Ataluren
Enrollment 246
Recruitment Details  
Pre-assignment Details All eligible participants, including those who received placebo in the double-blind study (PTC124-GD-021-CF; NCT02139306), were enrolled to this open-label extension study. To avoid interruption in treatment, when possible, Screening/Baseline for this extension study was to occur on the same day as the End-of-Study visit for the double-blind study.
Arm/Group Title Ataluren
Hide Arm/Group Description Participants were 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.
Period Title: Overall Study
Started 246
As-Treated Population [1] 245
Intent-to-treat (ITT) Population [2] 244
Completed 0
Not Completed 246
Reason Not Completed
Study Closure             207
Physician Decision             1
Required prohibited medications             5
Protocol Violation             1
Adverse Event             5
Abnormal Laboratory Value             2
Lost to Follow-up             1
Withdrawal by Subject             24
[1]
Participants who received at least 1 dose of ataluren.
[2]
Participants in the As-Treated Population with at least 1 postbaseline efficacy assessment.
Arm/Group Title Ataluren
Hide Arm/Group Description Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
Overall Number of Baseline Participants 245
Hide Baseline Analysis Population Description
Participants who received at least 1 dose of ataluren (As-Treated Population).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 245 participants
23.1  (10.88)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 245 participants
Female
113
  46.1%
Male
132
  53.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 245 participants
Asian 4
White 235
White-Arabic/North African Heritage 1
Non-White 5
Hispanic or Latino 16
Not Hispanic or Latino 229
1.Primary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of ataluren (As-Treated Population).
Arm/Group Title Ataluren
Hide Arm/Group Description:
Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
Overall Number of Participants Analyzed 245
Measure Type: Count of Participants
Unit of Measure: Participants
At least 1 TEAE
222
  90.6%
Mild TEAE
28
  11.4%
Moderate TEAE
147
  60.0%
Severe TEAE
46
  18.8%
Life-Threatening TEAE
1
   0.4%
Fatal TEAE
0
   0.0%
Serious TEAE
89
  36.3%
TEAE Unrelated to Study Drug
140
  57.1%
TEAE Unlikely Related to Study Drug
55
  22.4%
TEAE Possibly Related to Study Drug
23
   9.4%
TEAE Probably Related to Study Drug
4
   1.6%
2.Primary Outcome
Title Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Serum Biochemistry, Hematology, and Urinalysis) Parameter
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of ataluren (As-Treated Population).
Arm/Group Title Ataluren
Hide Arm/Group Description:
Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
Overall Number of Participants Analyzed 245
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
3.Secondary Outcome
Title Change From Baseline in Percent-Predicted Forced Expiratory Volume in 1 Second (FEV1) as Measured by Spirometry at Week 24
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of ataluren and have at least 1 postbaseline efficacy assessment (ITT Population) and had evaluable FEV1 data.
Arm/Group Title Ataluren
Hide Arm/Group Description:
Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
Overall Number of Participants Analyzed 233
Mean (Standard Deviation)
Unit of Measure: percentage of predicted FEV1
Baseline Number Analyzed 233 participants
60.219  (17.6163)
Change from Baseline at Week 24 Number Analyzed 205 participants
0.015  (6.7180)
4.Secondary Outcome
Title Change From Baseline in Percent-Predicted of Forced Vital Capacity (FVC) as Measured by Spirometry at Week 24
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of ataluren and have at least 1 postbaseline efficacy assessment (ITT Population) and had evaluable FVC data.
Arm/Group Title Ataluren
Hide Arm/Group Description:
Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
Overall Number of Participants Analyzed 233
Mean (Standard Deviation)
Unit of Measure: percentage of predicted FVC
Baseline Number Analyzed 233 participants
75.249  (15.8508)
Change from Baseline at Week 24 Number Analyzed 205 participants
0.166  (6.5276)
5.Secondary Outcome
Title Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) as Measured by Spirometry at Week 24
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of ataluren and have at least 1 postbaseline efficacy assessment (ITT Population) and had evaluable FEF25-75 data.
Arm/Group Title Ataluren
Hide Arm/Group Description:
Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
Overall Number of Participants Analyzed 233
Mean (Standard Deviation)
Unit of Measure: percentage of FEF25-75
Baseline Number Analyzed 233 participants
38.099  (22.0980)
Change from Baseline at Week 24 Number Analyzed 205 participants
0.698  (13.1241)
6.Secondary Outcome
Title Rate of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Over 48 Weeks
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of ataluren and have at least 1 postbaseline efficacy assessment (ITT Population).
Arm/Group Title Ataluren
Hide Arm/Group Description:
Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
Overall Number of Participants Analyzed 244
Mean (Standard Deviation)
Unit of Measure: exacerbations
1.051  (2.1654)
Time Frame Baseline up to Week 100
Adverse Event Reporting Description Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
 
Arm/Group Title Ataluren
Hide Arm/Group Description Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
All-Cause Mortality
Ataluren
Affected / at Risk (%)
Total   1/245 (0.41%) 
Hide Serious Adverse Events
Ataluren
Affected / at Risk (%)
Total   89/245 (36.33%) 
Congenital, familial and genetic disorders   
Cystic fibrosis lung  1  1/245 (0.41%) 
Gastrointestinal disorders   
Abdominal pain lower  1  1/245 (0.41%) 
Distal intestinal obstruction syndrome  1  1/245 (0.41%) 
Duodenal ulcer  1  1/245 (0.41%) 
Enteritis  1  1/245 (0.41%) 
Intestinal obstruction  1  3/245 (1.22%) 
Pancreatitis  1  1/245 (0.41%) 
Infections and infestations   
Bronchopulmonary aspergillosis allergic  1  1/245 (0.41%) 
Device related infection  1  1/245 (0.41%) 
Gastroenteritis viral  1  1/245 (0.41%) 
Infective pulmonary exacerbation of cystic fibrosis  1  63/245 (25.71%) 
Mycobacterium abscessus infection  1  1/245 (0.41%) 
Peritonitis  1  1/245 (0.41%) 
Pneumonia  1  1/245 (0.41%) 
Pseudomonas infection  1  1/245 (0.41%) 
Respiratory syncytial virus infection  1  1/245 (0.41%) 
Sinusitis  1  1/245 (0.41%) 
Viral pericarditis  1  1/245 (0.41%) 
Appendicitis  1  1/245 (0.41%) 
Investigations   
Forced expiratory volume decreased  1  2/245 (0.82%) 
Protein urine present  1  1/245 (0.41%) 
Pseudomonas test positive  1  1/245 (0.41%) 
Pulmonary function test decreased  1  1/245 (0.41%) 
Metabolism and nutrition disorders   
Dehydration  1  1/245 (0.41%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Squamous cell carcinoma of the cervix  1 [1]  1/113 (0.88%) 
Nervous system disorders   
Depressed level of consciousness  1  1/245 (0.41%) 
Pregnancy, puerperium and perinatal conditions   
Pregnancy  1 [1]  1/113 (0.88%) 
Renal and urinary disorders   
Nephrolithiasis  1  2/245 (0.82%) 
Renal colic  1  2/245 (0.82%) 
Renal failure acute  1  1/245 (0.41%) 
Respiratory, thoracic and mediastinal disorders   
Acute respiratory failure  1  1/245 (0.41%) 
Aspiration  1  1/245 (0.41%) 
Asthma  1  1/245 (0.41%) 
Dyspnoea exertional  1  1/245 (0.41%) 
Haemoptysis  1  4/245 (1.63%) 
1
Term from vocabulary, 17.0
Indicates events were collected by systematic assessment
[1]
This is a sex-specific adverse event that only affects female participants.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ataluren
Affected / at Risk (%)
Total   191/245 (77.96%) 
Gastrointestinal disorders   
Nausea  1  14/245 (5.71%) 
General disorders   
Pyrexia  1  13/245 (5.31%) 
Infections and infestations   
Infective pulmonary exacerbation of cystic fibrosis  1  136/245 (55.51%) 
Influenza  1  13/245 (5.31%) 
Sinusitis  1  25/245 (10.20%) 
Upper respiratory tract infection  1  21/245 (8.57%) 
Viral upper respiratory tract infection  1  30/245 (12.24%) 
Investigations   
Forced expiratory volume decreased  1  16/245 (6.53%) 
Nervous system disorders   
Headache  1  16/245 (6.53%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  32/245 (13.06%) 
Haemoptysis  1  14/245 (5.71%) 
1
Term from vocabulary, 17.0
Indicates events were collected by systematic assessment
This study was terminated early because the CF data from the double-blind CF Study PTC124-GD-021-CF (NCT02139306) did not meet endpoints.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor can review results and/or communications prior to public release and can embargo communications regarding trial results for a period that is up to 180 days from the time submitted to the Sponsor for review. The Sponsor may consult with the PI to require changes to the communication or extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Patient Advocacy
Organization: PTC Therapeutics, Inc.
Phone: 1-866-562-4620
EMail: medinfo@ptcbio.com
Layout table for additonal information
Responsible Party: PTC Therapeutics
ClinicalTrials.gov Identifier: NCT02456103    
Other Study ID Numbers: PTC124-GD-021e-CF
First Submitted: May 26, 2015
First Posted: May 28, 2015
Results First Submitted: April 1, 2020
Results First Posted: April 15, 2020
Last Update Posted: April 27, 2020