Extension Study of Ataluren in Participants With Nonsense Mutation Cystic Fibrosis

Phase 3

Terminated

• Conditions: Cystic Fibrosis
• Interventions: Drug: Ataluren

• Registration Number: NCT02456103
• Lead Sponsor: PTC Therapeutics

Brief Summary

This is an open-label extension study for participants who completed a Phase 3, placebo-controlled study of ataluren in participants with nonsense mutation cystic fibrosis (nmCF) not receiving chronic inhaled aminoglycosides.

Detailed Description

The primary objective of this Phase 3 extension study will be to obtain long-term safety data to augment the overall safety database. The secondary objectives will be to augment the efficacy data collected in the double-blind study (PTC124-GD-021-CF; NCT02139306).

Study Timeline

• Study First Submitted: 2015-05-26
• Study First Submitted QC: 2015-05-26
• Study First Posted: 2015-05-28
• Study Start: 2015-08-31
• Primary Completion: 2017-06-02
• Study Completion: 2017-06-02
• Disposition First Submitted: 2019-01-24
• Disposition First Submitted QC: 2019-01-24
• Disposition First Posted: 2019-01-28
• Status Verified: 2020-04
• Results First Submitted: 2020-04-01
• Results First Submitted QC: 2020-04-01
• Last Update Submitted: 2020-04-14
• Results First Posted: 2020-04-15
• Last Update Posted: 2020-04-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 246

Inclusion Criteria

• Completion of study treatment (placebo or active) in the previous Phase 3, double-blind study protocol (Protocol PTC124-GD-021-CF)
• Evidence of signed and dated informed consent/assent document(s) indicating that the participant (and/or the participant's parent/legal guardian) has been informed of all pertinent aspects of the trial.

Exclusion Criteria

• Known hypersensitivity to any of the ingredients or excipients of the study drug.
• Ongoing participation in any other therapeutic clinical trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ataluren	Ataluren	Participants will be 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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Serum Biochemistry, Hematology, and Urinalysis) Parameter	Baseline up to Week 100	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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	Baseline up to Week 100	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.

Secondary Outcome Measures

Name	Time	Method
Rate of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Over 48 Weeks	Baseline up to Week 48	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.
Change From Baseline in Percent-Predicted Forced Expiratory Volume in 1 Second (FEV1) as Measured by Spirometry at Week 24	Baseline, Week 24	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.
Change From Baseline in Percent-Predicted of Forced Vital Capacity (FVC) as Measured by Spirometry at Week 24	Baseline, Week 24	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.
Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) as Measured by Spirometry at Week 24	Baseline, Week 24	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.

Trial Locations

Locations (70)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Miller Children's Hospital Long Beach; 🇺🇸 Long Beach, California, United States

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Children's Hospital and Research Center at Oakland; 🇺🇸 Oakland, California, United States

Stanford University-Children's Hospital; 🇺🇸 Palo Alto, California, United States

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

Nemours Children's Clinic; 🇺🇸 Jacksonville, Florida, United States

University of Miami; 🇺🇸 Miami, Florida, United States

Miami Children's Hospital; 🇺🇸 Miami, Florida, United States

All Children's Hospital; 🇺🇸 Saint Petersburg, Florida, United States

Scroll for more (60 remaining)