Extension Study of Ataluren in Participants With Nonsense Mutation Cystic Fibrosis

Cystic Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02456103
• Other study ID #: PTC124-GD-021e-CF
• Status: Terminated
• Phase: Phase 3
• Start date: August 31, 2015
• Est. completion date: June 2, 2017

Study information

• Verified date: April 2020
• Source: PTC Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 246
• Est. completion date: June 2, 2017
• Est. primary completion date: June 2, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Ataluren
Ataluren will be provided as a vanilla-flavored powder to be mixed with water or milk.

Locations

Country	Name	City	State
Argentina	Hospital de Ninos Ricardo Gutierrez	Buenos Aires
Argentina	Hospital Universitario Austral	Buenos Aires
Australia	Royal Adelaide Hospital	Adelaide
Australia	Prince Charles Hospital	Chermside
Australia	Princess Margaret Hospital	Perth
Belgium	Hopital Universitaire des Enfants Reine Fabiola	Brussels
Belgium	University Hospital Brussels	Brussels
Belgium	University Hospital Leuven	Leuven
Brazil	Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul	Porto Alegre
Bulgaria	University Mulitiprofile Hospital for Active Treatment Sveti Georgi EAD	Plovdiv
Bulgaria	University Multiprofile Hospital for Active Treatment Aleksandrovska EAD	Sofia
Canada	Clinical Research Institute of Montreal	Montreal
Canada	University of Toronto Hospital for Sick Children	Toronto
Canada	British Columbia Children's Hospital	Vancouver
France	Hoptial Arnaud de Villeneuve	Montpellier
France	Hopital Necker - Enfants Malades	Paris
France	Centre de Perharidy	Roscoff
France	Centre Hospitalier Regional Sud Reunion	Saint-Pierre
Germany	Charite-Universitatsmedizin Berlin	Berlin
Germany	St. Josef Hospital GmbH	Bochum
Germany	University of Cologne Children's Hospital	Cologne
Germany	Christiane Herzog CF-Zentrum	Frankfurt am Main
Germany	Universitatsklinikum Jena	Jena
Germany	Dr. Von Haunersches Kinderspital	Munchen
Germany	LMU Klinikum der Universitat Muchen	Munich
Greece	Ippokratio General Hospital Of Thessaloniki	Thessaloniki
Israel	Meyer Children's Hospital	Haifa
Israel	Hadassah University Hospital	Jerusalem
Italy	Azienda Ospedaliero Universitaria Ospedall Riuniti di Acona-Umberto I G.M. Lancisi G. Salesi	Ancona
Italy	Azienda Ospedaliera A Meyer	Firenze
Italy	Lombardia Cystic Fibrosis Center	Milan
Italy	Azienda Policlinico Umberto I	Rome
Italy	Ospedale Pediatrico Bambino Gesu	Rome
Italy	Azienda Ospedaliera di Verona	Verona
Netherlands	Radboud University	Nijmegen
Netherlands	Hagaziekenhuis	s-Gravenweg	Zuid-Holland
Poland	Szpital Dzieciecy Polanki im Macieja Plazynskiego w Gdansku	Gdansk
Poland	Institute of Mother and Child	Warsaw
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital University	Barcelona
Spain	Hospital San Juan	Esplugues De Llobregat
Spain	Hospital Regional Universitario de Malaga	Malaga
Spain	Hospital de Sabadell, Consorci Sanitari Parc Tauli	Sabadell
Spain	Hospital Universitario Virgen del Rocio	Sevilla
United Kingdom	St James University Hospital	Leeds
United Kingdom	Royal Brompton Hospital	London
United States	Children's Hospital Colorado	Aurora	Colorado
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Texas Children's Hospital	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	Miller Children's Hospital Long Beach	Long Beach	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Miami Children's Hospital	Miami	Florida
United States	University of Miami	Miami	Florida
United States	Childrens Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Morristown Medical Center	Morristown	New Jersey
United States	Beth Israel Medical Center	New York	New York
United States	Columbia University Medical Center	New York	New York
United States	New York University Langone Medical Center	New York	New York
United States	Children's Hospital and Research Center at Oakland	Oakland	California
United States	Stanford University-Children's Hospital	Palo Alto	California
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	All Children's Hospital	Saint Petersburg	Florida
United States	University of Texas Health Science Center	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
PTC Therapeutics

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  France,  Germany,  Greece,  Israel,  Italy,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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