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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

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 61
Recruitment Details Participants with nonsense mutation cystic fibrosis (nmCF) who had completed the double-blind study PTC124-GD-009-CF (NCT00803205) were enrolled and treated in this open-label extension study.
Pre-assignment Details On 2 March 2017, it was announced that the Phase 3 double-blind study PTC124-GD-021-CF (NCT02139306) did not achieve its primary or secondary endpoints. Based on these results, clinical development of ataluren in cystic fibrosis was discontinued and this ongoing open-label extension study was closed.
Arm/Group Title Ataluren
Hide Arm/Group Description Participants received 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.
Period Title: Overall Study
Started 61
As-treated Population [1] 61
Intent-to-treat (ITT) Population [2] 60
Completed 0
Not Completed 61
Reason Not Completed
Withdrawal by Subject             14
Adverse Event             3
Study closure             41
Other than specified             3
[1]
Received at .least 1 dose of study drug
[2]
All participants who had at least 1 post-baseline efficacy assessment.
Arm/Group Title Ataluren
Hide Arm/Group Description Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Overall Number of Baseline Participants 61
Hide Baseline Analysis Population Description
As-treated population included all participants who received at least 1 dose of ataluren.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 61 participants
27.5  (10.73)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants
Female
34
  55.7%
Male
27
  44.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants
Hispanic or Latino
1
   1.6%
Not Hispanic or Latino
60
  98.4%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants
White-White/Caucasian
61
 100.0%
1.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received at least 1 dose of ataluren.
Arm/Group Title Ataluren
Hide Arm/Group Description:
Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Overall Number of Participants Analyzed 61
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAEs
61
 100.0%
Mild AEs
4
   6.6%
Moderate AEs
26
  42.6%
Severe AEs
30
  49.2%
Life-threatening AEs
0
   0.0%
Fatal AEs
1
   1.6%
AEs unrelated to ataluren
35
  57.4%
AEs unlikely related to ataluren
12
  19.7%
AEs possible related to ataluren
13
  21.3%
AEs probable related to ataluren
1
   1.6%
Serious TEAEs
36
  59.0%
2.Primary Outcome
Title Number of Participants With Clinically Significant Laboratory Abnormalities
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received at least 1 dose of ataluren.
Arm/Group Title Ataluren
Hide Arm/Group Description:
Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Overall Number of Participants Analyzed 61
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) at the End of Treatment (Week 192), as Assessed by Spirometry
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who had at least 1 post-baseline efficacy assessment. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint.
Arm/Group Title Ataluren
Hide Arm/Group Description:
Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Overall Number of Participants Analyzed 59
Mean (Standard Deviation)
Unit of Measure: percentage of predicted FEV1
Baseline Number Analyzed 59 participants
56.203  (17.2964)
Change at Week 192 Number Analyzed 7 participants
-1.214  (3.6384)
4.Secondary Outcome
Title Percentage of Participants With Pulmonary Exacerbation, As Assessed by Modified Fuchs Criteria
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who had at least 1 post-baseline efficacy assessment.
Arm/Group Title Ataluren
Hide Arm/Group Description:
Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Overall Number of Participants Analyzed 60
Measure Type: Number
Unit of Measure: percentage of participants
68.3
5.Secondary Outcome
Title Percentage of Participants With Pulmonary Exacerbation, As Assessed by Expanded Fuchs' Criteria
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who had at least 1 post-baseline efficacy assessment.
Arm/Group Title Ataluren
Hide Arm/Group Description:
Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Overall Number of Participants Analyzed 60
Measure Type: Number
Unit of Measure: percentage of participants
68.3
6.Secondary Outcome
Title Percentage of Participants With Pulmonary Exacerbation, As Assessed by Classic Fuchs' Criteria
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who had at least 1 post-baseline efficacy assessment.
Arm/Group Title Ataluren
Hide Arm/Group Description:
Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Overall Number of Participants Analyzed 60
Measure Type: Number
Unit of Measure: percentage of participants
58.3
7.Secondary Outcome
Title Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters at Final Visit (Week 196)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received at least 1 dose of ataluren. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified categories.
Arm/Group Title Ataluren
Hide Arm/Group Description:
Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Overall Number of Participants Analyzed 59
Mean (Standard Deviation)
Unit of Measure: miiliseconds
Baseline: RR duration Number Analyzed 59 participants
828.17  (132.15)
Change at Week 196: RR duration Number Analyzed 55 participants
-14.27  (115.62)
Baseline: PR duration Number Analyzed 59 participants
145.02  (19.29)
Change at Week 196: PR duration Number Analyzed 55 participants
-2.69  (12.25)
Baseline: QRS duration Number Analyzed 59 participants
83.90  (8.00)
Change at Week 196: QRS duration Number Analyzed 55 participants
0.33  (6.12)
Baseline: QT duration Number Analyzed 59 participants
370.71  (28.11)
Change at Week 196: QT duration Number Analyzed 55 participants
-4.38  (25.63)
Baseline: QTCB duration Number Analyzed 59 participants
408.92  (22.05)
Change at Week 196: QTCB duration Number Analyzed 55 participants
-0.71  (17.96)
Baseline: QTCF duration Number Analyzed 59 participants
395.47  (19.23)
Change at Week 196: QTCF duration Number Analyzed 59 participants
-2.27  (17.13)
8.Secondary Outcome
Title Change From Baseline in Heart Rate at Final Visit (Week 196), as Assessed by 12-Lead ECG
Hide Description Heart rate was measured using 12-lead ECG.
Time Frame Baseline, Week 196
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received at least 1 dose of ataluren. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified categories.
Arm/Group Title Ataluren
Hide Arm/Group Description:
Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Overall Number of Participants Analyzed 59
Mean (Standard Deviation)
Unit of Measure: beats/minute
Baseline Number Analyzed 59 participants
74.31  (12.06)
Change at Week 196 Number Analyzed 55 participants
2.04  (10.11)
9.Secondary Outcome
Title Change From Baseline in Vital Signs at Final Visit (Week 196)
Hide Description Vital Signs included systolic blood pressure (SBP) and diastolic blood pressure (DBP).
Time Frame Baseline, Week 196
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received at least 1 dose of ataluren. Here, 'Number analyzed' signifies participants evaluable for specified categories.
Arm/Group Title Ataluren
Hide Arm/Group Description:
Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Overall Number of Participants Analyzed 61
Mean (Standard Deviation)
Unit of Measure: millimeters of mercury (mmHg)
Baseline: SBP Number Analyzed 61 participants
114.8  (9.10)
Change at Week 196: SBP Number Analyzed 59 participants
0.6  (12.62)
Baseline: DBP Number Analyzed 61 participants
71.2  (8.93)
Change at Week 196: DBP Number Analyzed 59 participants
-0.3  (9.93)
10.Other Pre-specified Outcome
Title Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at the End of Treatment (Week 192), as Assessed by Spirometry
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who had at least 1 post-baseline efficacy assessment. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint.
Arm/Group Title Ataluren
Hide Arm/Group Description:
Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Overall Number of Participants Analyzed 59
Mean (Standard Deviation)
Unit of Measure: percentage of predicted FVC
Baseline Number Analyzed 59 participants
73.576  (14.6552)
Change at Week 192 Number Analyzed 7 participants
-2.286  (4.5722)
11.Other Pre-specified Outcome
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
Hide Description FEF25-75 is the forced expiratory flow between 25 and 75% of vital capacity.
Time Frame Baseline, Week 192
Hide Outcome Measure Data
Hide Analysis Population Description
Due to change in planned analysis FEV25-75 was not calculated and summarized.
Arm/Group Title Ataluren
Hide Arm/Group Description:
Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Baseline up to end of study (Week 196)
Adverse Event Reporting Description As-treated population included all participants who received at least 1 dose of ataluren.
 
Arm/Group Title Ataluren
Hide Arm/Group Description Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
All-Cause Mortality
Ataluren
Affected / at Risk (%)
Total   1/61 (1.64%) 
Hide Serious Adverse Events
Ataluren
Affected / at Risk (%)
Total   36/61 (59.02%) 
Congenital, familial and genetic disorders   
Cystic fibrosis  1  1/61 (1.64%) 
Gastrointestinal disorders   
Constipation  1  1/61 (1.64%) 
Distal ileal obstruction syndrome  1  1/61 (1.64%) 
Distal intestinal obstruction syndrome  1  3/61 (4.92%) 
Intestinal obstruction  1  1/61 (1.64%) 
Hepatobiliary disorders   
Gallbladder pain  1  1/61 (1.64%) 
Infections and infestations   
Appendicitis  1  1/61 (1.64%) 
Cellulitis  1  1/61 (1.64%) 
Clostridium difficile infection  1  1/61 (1.64%) 
Device related infection  1  1/61 (1.64%) 
Infective pulmonary exacerbation of cystic fibrosis  1  27/61 (44.26%) 
Viral upper respiratory tract infection  1  1/61 (1.64%) 
Injury, poisoning and procedural complications   
Femur fracture  1  1/61 (1.64%) 
Investigations   
Blood creatine increased  1  1/61 (1.64%) 
Forced expiratory volume decreased  1  2/61 (3.28%) 
Pulmonary function test decreased  1  1/61 (1.64%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Colon cancer  1  1/61 (1.64%) 
Renal and urinary disorders   
Renal failure  1  1/61 (1.64%) 
Renal failure acute  1  1/61 (1.64%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  1/61 (1.64%) 
Haemoptysis  1  7/61 (11.48%) 
Pneumothorax  1  1/61 (1.64%) 
Respiratory failure  1  1/61 (1.64%) 
Vascular disorders   
Deep vein thrombosis  1  1/61 (1.64%) 
1
Term from vocabulary, MedDRA 17.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ataluren
Affected / at Risk (%)
Total   61/61 (100.00%) 
Gastrointestinal disorders   
Abdominal pain  1  6/61 (9.84%) 
Abdominal pain upper  1  5/61 (8.20%) 
Constipation  1  7/61 (11.48%) 
Diarrhoea  1  8/61 (13.11%) 
Haemorrhoids  1  4/61 (6.56%) 
Nausea  1  6/61 (9.84%) 
Vomiting  1  4/61 (6.56%) 
Immune system disorders   
Drug hypersensitivity  1  5/61 (8.20%) 
Infections and infestations   
Gastroenteritis  1  5/61 (8.20%) 
Infective pulmonary exacerbation of cystic fibrosis  1  50/61 (81.97%) 
Influenza  1  4/61 (6.56%) 
Nasopharyngitis  1  5/61 (8.20%) 
Oral candidiasis  1  4/61 (6.56%) 
Sinusitis  1  6/61 (9.84%) 
Upper respiratory tract infection  1  9/61 (14.75%) 
Viral upper respiratory tract infection  1  22/61 (36.07%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  5/61 (8.20%) 
Back pain  1  5/61 (8.20%) 
Musculoskeletal chest pain  1  4/61 (6.56%) 
Nervous system disorders   
Headache  1  5/61 (8.20%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  9/61 (14.75%) 
Haemoptysis  1  12/61 (19.67%) 
1
Term from vocabulary, MedDRA 17.0
Indicates events were collected by systematic assessment
Based on the results of study PTC124-GD-021-CF (NCT02139306) (did not achieve its primary or secondary endpoints), clinical development of ataluren in cystic fibrosis was discontinued and this ongoing open-label extension study was closed.
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: NCT02107859    
Other Study ID Numbers: PTC124-GD-023-CF
2013-005449-35 ( EudraCT Number )
First Submitted: April 4, 2014
First Posted: April 8, 2014
Results First Submitted: March 11, 2020
Results First Posted: March 25, 2020
Last Update Posted: March 25, 2020