Study of Ataluren (PTC124) in Cystic Fibrosis

NCT02107859 | Terminated Phase 3 Results DMC

• 2 other identifiers: PTC124-GD-023-CF2013-005449-35
• Study Type: interventional
• Target: 61
• Locations: 7 countries
• Sites: 17

Brief Summary

The primary objective of this study is to determine the long-term safety and tolerability of ataluren in participants with nonsense mutation cystic fibrosis (nmCF) who completed participation in the double-blind study PTC124-GD-009-CF (NCT00803205), as assessed by adverse events and laboratory abnormalities. The secondary objective of this study includes the assessment of the efficacy of ataluren, as measured by forced expiratory volume in 1 second (FEV1) and pulmonary exacerbation rate, and other safety parameters (for example, 12-lead electrocardiogram \[ECG\] measurements, vital signs).

Conditions

Cystic Fibrosis

Keywords

Cystic fibrosis; Nonsense mutation; Premature stop codon; PTC124; Ataluren

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  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.

  Baseline (Day 1) up to end of study (Week 196)

• Number of Participants With Clinically Significant Laboratory Abnormalities

  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.

  Baseline (Day 1) up to end of study (Week 196)

Secondary Outcomes (7)

• Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at the End of Treatment (Week 192), as Assessed by Spirometry

  Baseline, Week 192

• Percentage of Participants With Pulmonary Exacerbation, As Assessed by Modified Fuchs Criteria

  Baseline up to Week 192

• Percentage of Participants With Pulmonary Exacerbation, As Assessed by Expanded Fuchs' Criteria

  Baseline up to Week 192

• Percentage of Participants With Pulmonary Exacerbation, As Assessed by Classic Fuchs' Criteria

  Baseline up to Week 192

• Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters at Final Visit (Week 196)

  Baseline, Week 196

Other Outcomes (2)

• Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at the End of Treatment (Week 192), as Assessed by Spirometry

  Baseline, Week 192

• 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

  Baseline, Week 192

Study Arms (1)

Ataluren

EXPERIMENTAL

Participants will receive 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.

Drug: Ataluren

Interventions

Ataluren DRUG

Ataluren will be administered per dose and schedule specified in the arm.

Also known as: PTC124

Ataluren

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide written informed consent (parental/guardian consent and participant assent if less than \[\<\] 18 years of age).
• Evidence of completed participation in the double-blind study, PTC124-GD-009-CF (Study 009).
• Body weight greater than or equal to (≥) 16 kilograms (kg).
• Performance of a valid, reproducible spirometry test using the study-specific spirometer during the screening period.
• Confirmed laboratory values within the central laboratory ranges at screening.
• In male and female participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and 60-day follow-up period.
• Willingness and ability to comply with all study procedures and assessments, including scheduled visits, drug administration plan, laboratory tests, and study restrictions.

You may not qualify if:

• Chronic use of systemic tobramycin within 4 weeks prior to screening.
• Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection (including viral illnesses) within 3 weeks prior to screening or between screening and randomization.
• Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or re-initiation) in a chronic treatment/prophylaxis regimen for CF or for CF-related conditions within 4 weeks prior to screening and randomization.
• Known hypersensitivity to any of the ingredients or excipients of the study drug.
• Exposure to another investigational drug within 4 weeks prior to screening.
• Treatment with intravenous antibiotics within 3 weeks prior to screening.
• History of solid organ or hematological transplantation.
• Ongoing immunosuppressive therapy (other than corticosteroids).
• Positive hepatitis B surface antigen, hepatitis C antibody test or human immunodeficiency virus (HIV) test.
• Known portal hypertension.
• Pregnancy or breast-feeding.

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (17)

University of Alabama-Birmingham

Birmingham, Alabama, 35233, United States

Location

Miller Children's Hospital Long Beach

Long Beach, California, 90806, United States

Location

Denver Children's Hospital

Aurora, Colorado, 80045, United States

Location

Children's Hospital Chicago

Chicago, Illinois, 60614, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

Rainbow Babies & Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Hôpital Universitaire des Enfants Reine Fabiola

Brussels, Belgium

Location

University Hospital Brussels

Brussels, Belgium

Location

University Hospital Leuven

Leuven, Belgium

Location

Hôpital Necker - Enfants Malades

Paris, France

Location

Hôpital des Enfants

Toulouse, 31059, France

Location

Hadassah University Hospital - Mount Scopus

Jerusalem, 91240, Israel

Location

Università La Sapienza

Roma, Italy

Location

Azienda Ospedaliera di Verona

Verona, Italy

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Karolinska University Hospital, Huddinge

Stockholm, Sweden

Location

Related Publications (1)

• Aslam AA, Sinha IP, Southern KW. Ataluren and similar compounds (specific therapies for premature termination codon class I mutations) for cystic fibrosis. Cochrane Database Syst Rev. 2023 Mar 3;3(3):CD012040. doi: 10.1002/14651858.CD012040.pub3.

  PMID: 36866921 DERIVED

Related Links

• PTC Therapeutics, Inc. website

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

ataluren

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Patient Advocacy
• Organization: PTC Therapeutics, Inc.

medinfo@ptcbio.com

1-866-562-4620

Study Officials

• Joseph McIntosh, MD

  PTC Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2014
• First Posted: April 8, 2014
• Study Start: May 23, 2014
• Primary Completion: June 5, 2017
• Study Completion: June 5, 2017
• Last Updated: March 25, 2020
• Results First Posted: March 25, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (3); US (7); FR (2); IL (1); SE (1); ES (1); IT (2)