Trial Outcomes & Findings for Extension Study of Ataluren in Participants With Nonsense Mutation Cystic Fibrosis (NCT NCT02456103)
NCT ID: NCT02456103
Last Updated: 2020-04-27
Results Overview
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.
TERMINATED
PHASE3
246 participants
Baseline up to Week 100
2020-04-27
Participant Flow
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.
Participant milestones
| Measure |
Ataluren
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.
|
|---|---|
|
Overall Study
STARTED
|
246
|
|
Overall Study
As-Treated Population
|
245
|
|
Overall Study
Intent-to-treat (ITT) Population
|
244
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
246
|
Reasons for withdrawal
| Measure |
Ataluren
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.
|
|---|---|
|
Overall Study
Study Closure
|
207
|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
Required prohibited medications
|
5
|
|
Overall Study
Protocol Violation
|
1
|
|
Overall Study
Adverse Event
|
5
|
|
Overall Study
Abnormal Laboratory Value
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Withdrawal by Subject
|
24
|
Baseline Characteristics
Extension Study of Ataluren in Participants With Nonsense Mutation Cystic Fibrosis
Baseline characteristics by cohort
| Measure |
Ataluren
n=245 Participants
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.
|
|---|---|
|
Age, Continuous
|
23.1 years
STANDARD_DEVIATION 10.88 • n=5 Participants
|
|
Sex: Female, Male
Female
|
113 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
132 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
4 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
235 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White-Arabic/North African Heritage
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Non-White
|
5 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
16 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
229 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 100Population: Participants who received at least 1 dose of ataluren (As-Treated Population).
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.
Outcome measures
| Measure |
Ataluren
n=245 Participants
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.
|
|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
At least 1 TEAE
|
222 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Mild TEAE
|
28 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Moderate TEAE
|
147 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Severe TEAE
|
46 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Life-Threatening TEAE
|
1 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Fatal TEAE
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Serious TEAE
|
89 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
TEAE Unrelated to Study Drug
|
140 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
TEAE Unlikely Related to Study Drug
|
55 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
TEAE Possibly Related to Study Drug
|
23 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
TEAE Probably Related to Study Drug
|
4 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 100Population: Participants who received at least 1 dose of ataluren (As-Treated Population).
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.
Outcome measures
| Measure |
Ataluren
n=245 Participants
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.
|
|---|---|
|
Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Serum Biochemistry, Hematology, and Urinalysis) Parameter
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Participants who received at least 1 dose of ataluren and have at least 1 postbaseline efficacy assessment (ITT Population) and had evaluable FEV1 data.
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.
Outcome measures
| Measure |
Ataluren
n=233 Participants
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.
|
|---|---|
|
Change From Baseline in Percent-Predicted Forced Expiratory Volume in 1 Second (FEV1) as Measured by Spirometry at Week 24
Baseline
|
60.219 percentage of predicted FEV1
Standard Deviation 17.6163
|
|
Change From Baseline in Percent-Predicted Forced Expiratory Volume in 1 Second (FEV1) as Measured by Spirometry at Week 24
Change from Baseline at Week 24
|
0.015 percentage of predicted FEV1
Standard Deviation 6.7180
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Participants who received at least 1 dose of ataluren and have at least 1 postbaseline efficacy assessment (ITT Population) and had evaluable FVC data.
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.
Outcome measures
| Measure |
Ataluren
n=233 Participants
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.
|
|---|---|
|
Change From Baseline in Percent-Predicted of Forced Vital Capacity (FVC) as Measured by Spirometry at Week 24
Baseline
|
75.249 percentage of predicted FVC
Standard Deviation 15.8508
|
|
Change From Baseline in Percent-Predicted of Forced Vital Capacity (FVC) as Measured by Spirometry at Week 24
Change from Baseline at Week 24
|
0.166 percentage of predicted FVC
Standard Deviation 6.5276
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Ataluren
n=233 Participants
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.
|
|---|---|
|
Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) as Measured by Spirometry at Week 24
Baseline
|
38.099 percentage of FEF25-75
Standard Deviation 22.0980
|
|
Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) as Measured by Spirometry at Week 24
Change from Baseline at Week 24
|
0.698 percentage of FEF25-75
Standard Deviation 13.1241
|
SECONDARY outcome
Timeframe: Baseline up to Week 48Population: Participants who received at least 1 dose of ataluren and have at least 1 postbaseline efficacy assessment (ITT Population).
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.
Outcome measures
| Measure |
Ataluren
n=244 Participants
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.
|
|---|---|
|
Rate of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Over 48 Weeks
|
1.051 exacerbations
Standard Deviation 2.1654
|
Adverse Events
Ataluren
Serious adverse events
| Measure |
Ataluren
n=245 participants at risk
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.
|
|---|---|
|
Infections and infestations
Bronchopulmonary aspergillosis allergic
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Infections and infestations
Device related infection
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Infections and infestations
Gastroenteritis viral
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
25.7%
63/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Infections and infestations
Mycobacterium abscessus infection
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Infections and infestations
Peritonitis
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Infections and infestations
Pneumonia
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Infections and infestations
Pseudomonas infection
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Infections and infestations
Respiratory syncytial virus infection
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Infections and infestations
Sinusitis
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Infections and infestations
Viral pericarditis
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Gastrointestinal disorders
Distal intestinal obstruction syndrome
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Gastrointestinal disorders
Enteritis
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Gastrointestinal disorders
Intestinal obstruction
|
1.2%
3/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Gastrointestinal disorders
Pancreatitis
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.6%
4/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Investigations
Forced expiratory volume decreased
|
0.82%
2/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Investigations
Protein urine present
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Investigations
Pseudomonas test positive
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Investigations
Pulmonary function test decreased
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.82%
2/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Renal and urinary disorders
Renal colic
|
0.82%
2/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Renal and urinary disorders
Renal failure acute
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Congenital, familial and genetic disorders
Cystic fibrosis lung
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Metabolism and nutrition disorders
Dehydration
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of the cervix
|
0.88%
1/113 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Nervous system disorders
Depressed level of consciousness
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.88%
1/113 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Infections and infestations
Appendicitis
|
0.41%
1/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
Other adverse events
| Measure |
Ataluren
n=245 participants at risk
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.
|
|---|---|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
55.5%
136/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Infections and infestations
Influenza
|
5.3%
13/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Infections and infestations
Sinusitis
|
10.2%
25/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Infections and infestations
Upper respiratory tract infection
|
8.6%
21/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Infections and infestations
Viral upper respiratory tract infection
|
12.2%
30/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.1%
32/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
5.7%
14/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Investigations
Forced expiratory volume decreased
|
6.5%
16/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Nervous system disorders
Headache
|
6.5%
16/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
Gastrointestinal disorders
Nausea
|
5.7%
14/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
|
General disorders
Pyrexia
|
5.3%
13/245 • Baseline up to Week 100
Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER