Extension Study of Ataluren in Participants With Nonsense Mutation Cystic Fibrosis

Phase 3 Extension Study of Ataluren (PTC124) in Patients With Nonsense Mutation Cystic Fibrosis

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.

Study Overview

• Status: Terminated
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Ataluren

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 Type: Interventional
• Enrollment (Actual): 246
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Hospital Universitario Austral
  • Buenos Aires, Argentina, 1330
    • Hospital de Niños Ricardo Gutiérrez
• Australia
  • Adelaide, Australia, 5000
    • Royal Adelaide Hospital
  • Chermside, Australia, 4032
    • Prince Charles Hospital
  • Perth, Australia, 6840
    • Princess Margaret Hospital
• Belgium
  • Brussels, Belgium, 1090
    • University Hospital Brussels
  • Brussels, Belgium, 15
    • Hôpital Universitaire des Enfants Reine Fabiola
  • Leuven, Belgium, 3000
    • University Hospital Leuven
• Brazil
  • Porto Alegre, Brazil
    • Hospital Sao Lucas da Pontificia Universidade Catolica do Rio Grande do Sul
• Bulgaria
  • Plovdiv, Bulgaria
    • University Mulitiprofile Hospital for Active Treatment Sveti Georgi EAD
  • Sofia, Bulgaria
    • University Multiprofile Hospital for Active Treatment Aleksandrovska EAD
• Canada
  • Montreal, Canada, H2W 1R7
    • Clinical Research Institute of Montreal
  • Toronto, Canada, M5G 1X8
    • University of Toronto Hospital for Sick Children
  • Vancouver, Canada, V6H 3V4
    • British Columbia Children's Hospital
• France
  • Montpellier, France, 34295
    • Hoptial Arnaud de Villeneuve
  • Paris, France, 75015
    • Hôpital Necker - Enfants Malades
  • Roscoff, France, 29684
    • Centre de Perharidy
  • Saint-Pierre, France, 97448
    • Centre Hospitalier Regional Sud Reunion
• Germany
  • Berlin, Germany, 10117
    • Charite-Universitatsmedizin Berlin
  • Bochum, Germany, 44791
    • St. Josef Hospital GmbH
  • Cologne, Germany, 50937
    • University of Cologne Children's Hospital
  • Frankfurt am Main, Germany, 60590
    • Christiane Herzog CF-Zentrum
  • Jena, Germany, 1
    • Universitätsklinikum Jena
  • Munchen, Germany, 80337
    • Dr. von Haunersches Kinderspital
  • Munich, Germany, 80539
    • LMU Klinikum der Universitat Muchen
• Greece
  • Thessaloniki, Greece, 541
    • Ippokratio General Hospital of Thessaloniki
• Israel
  • Haifa, Israel, 31096
    • Meyer Children's Hospital
  • Jerusalem, Israel, 91240
    • Hadassah University Hospital
• Italy
  • Ancona, Italy, 71
    • Azienda Ospedaliero Universitaria Ospedall Riuniti di Acona-Umberto I G.M. Lancisi G. Salesi
  • Firenze, Italy, 50139
    • Azienda Ospedaliera A Meyer
  • Milan, Italy, 20122
    • Lombardia Cystic Fibrosis Center
  • Rome, Italy, 00161
    • Azienda Policlinico Umberto I
  • Rome, Italy, 4
    • Ospedale Pediatrico Bambino Gesù
  • Verona, Italy
    • Azienda Ospedaliera di Verona
• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Radboud University
  • Zuid-Holland
    • s-Gravenweg, Zuid-Holland, Netherlands, 2545 CH
      • HagaZiekenhuis
• Poland
  • Gdansk, Poland
    • Szpital Dzieciecy Polanki im Macieja Plazynskiego w Gdansku
  • Warsaw, Poland, 01-211
    • Institute of Mother and Child
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08035
    • Hospital University
  • Esplugues De Llobregat, Spain, 08950
    • Hospital San Juan
  • Malaga, Spain, 29001
    • Hospital Regional Universitario de Málaga
  • Sabadell, Spain, 08208
    • Hospital de Sabadell, Consorci Sanitari Parc Tauli
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • St James University Hospital
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Long Beach, California, United States, 90806
      • Miller Children's Hospital Long Beach
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Oakland, California, United States, 94609
      • Children's Hospital and Research Center at Oakland
    • Palo Alto, California, United States, 94304
      • Stanford University-Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
    • Saint Petersburg, Florida, United States, 33701
      • All Children's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann and Robert H. Lurie Children's Hospital of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital Boston
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
    • New York, New York, United States, 10011
      • Beth Israel Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45221
      • University of Cincinnati
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19129
      • Drexel University College of Medicine
  • Texas
    • Houston, Texas, United States, 77094
      • Texas Children's Hospital
    • Tyler, Texas, United States, 75708
      • University of Texas Health Science Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Childrens Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Ataluren; Ataluren will be provided as a vanilla-flavored powder to be mixed with water or milk.; Other Names: PTC124; Translarna

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: PTC Therapeutics
• Investigators: Study Director: Joseph McIntosh, MD, PTC Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2015
• Primary Completion (Actual): June 2, 2017
• Study Completion (Actual): June 2, 2017

Study Registration Dates

• First Submitted: May 26, 2015
• First Submitted That Met QC Criteria: May 26, 2015
• First Posted (Estimate): May 28, 2015

Study Record Updates

• Last Update Posted (Actual): April 27, 2020
• Last Update Submitted That Met QC Criteria: April 14, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: PTC124-GD-021e-CF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO