Extension Study of Ataluren (PTC124) in Cystic Fibrosis

NCT01140451 | Completed Phase 3 Results DMC

• 3 other identifiers: PTC124-GD-009e-CFOrphan Product Grant #FD0037152010-019692-30
• Study Type: interventional
• Target: 191
• Locations: 11 countries
• Sites: 31

Brief Summary

Cystic fibrosis (CF) is a genetic disorder caused by a mutation in the gene that makes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A specific type of mutation called a nonsense (premature stop codon) mutation is the cause of CF in approximately 10% of patients with the disease. Ataluren is an orally delivered investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 3 extension trial that will evaluate the long-term safety of ataluren in adult and pediatric participants with nonsense mutation CF (nmCF), as determined by adverse events and laboratory abnormalities. The study will also assess changes in pulmonary function, CF pulmonary exacerbations, health-related quality of life, antibiotic use for CF-related infections, CF-related disruptions to daily living, body weight, and CF pathophysiology. Funding source for this study is the FDA OOPD.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (2)

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

  A TEAE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship that occurred or worsened in the period extending from the first dose of study drug to 6 weeks after the last dose of study drug. A serious adverse event (SAE) was an adverse event (AE) resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. AE severity was graded as follows: Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening; Grade 5: fatal. A TEAE was considered related if in the opinion of the Investigator it was possibly or probably caused by the study drug. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the Adverse Events module.

  Baseline (Week 1 [Total Study Week 48]) up to 4 Weeks Post-Treatment (Week 100 [Total Study Week 148]) or Premature Discontinuation (PD) (whichever occurred first)

• Number of Participants With Any Treatment-Emergent Laboratory Abnormality (TELA)

  A TELA is any abnormal laboratory value that started or worsened after administration of study drug. Abnormal values were defined as values outside normal range. Values considered abnormal included -Hepatic: Serum total bilirubin ≥1.5\*upper limit of normal (ULN); serum gamma glutamyl transferase \>2.5\*ULN; serum alanine aminotransferase increase of \>150 units/liter (U/L) without increased creatine kinase; -Adrenal: plasma adrenocorticotropic hormone \>ULN (normal cortisol); -Renal: serum cystatin C \>1.33 milligrams (mg)/L; serum creatinine \>ULN-1.5\*ULN for age; serum blood urea nitrogen ≥1.5\*ULN; urine protein:creatinine \>0.40 mg/deciliter (dL):mg/dL; urine protein:osmolality \>0.30 mg/L:milliosmoles/kilogram; urine blood 2+; - Serum Electrolytes: serum sodium \>150 millimoles (mmol)/L, \<130 mmol/L; serum potassium \>5.5, \<3.0 mmol/L; serum magnesium \>1.23 mmol/L, \<0.5 mmol/L; total serum calcium \>2.9 mmol/L, \<2.0 mmol/L; serum phosphorous \<0.8 mmol/L; serum biocarbonate- \<16 mmol/L.

  Baseline (Week 1 [Total Study Week 48]) up to 4 Weeks Post-Treatment (Week 100 [Total Study Week 148]) or PD (whichever occurred first)

Secondary Outcomes (21)

• Percentage of Predicted Function (Percent-Predicted) of Forced Expiratory Volume in 1 Second (FEV1) at Baseline

  Baseline (Week 1 [Total Study Week 48])

• Percentage Change From Baseline in Percent-Predicted of FEV1 at Weeks 48 and 96

  Week 48 (Total Study Week 96), End of Treatment (EOT) (Week 96 [Total Study Week 144])

• Percent-Predicted of Forced Vital Capacity (FVC) at Baseline

  Baseline (Week 1 [Total Study Week 48])

• Percentage Change From Baseline in Percent-Predicted of FVC at Weeks 48 and 96

  Week 48 (Total Study Week 96), EOT (Week 96 [Total Study Week 144])

• Percent-Predicted of Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) at Baseline

  Baseline (Week 1 [Total Study Week 48])

Study Arms (2)

Ataluren/Ataluren

EXPERIMENTAL

Participants who received double-blind ataluren during Study 009 will continue to receive open-label ataluren 3 times per day TID: 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants will be followed for 4 weeks after treatment.

Drug: Ataluren

Placebo/Ataluren

EXPERIMENTAL

Participants who received double-blind placebo during Study 009 will receive open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants will be followed for 4 weeks after treatment.

Drug: Ataluren

Interventions

Ataluren DRUG

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

Also known as: PTC124

Ataluren/Ataluren; Placebo/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:

• Completion of blinded study drug treatment in the previous Phase 3 study (PTC124-GD-009-CF).
• Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if \<18 years of age).
• In participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during ataluren administration and the 4-week follow up period.
• Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.

You may not qualify if:

• Known hypersensitivity to any of the ingredients or excipients of the study drug (list provided at study sites).
• Current pregnancy or lactating, or pregnancy or lactating during the previous Phase 3 study.
• Ongoing participation in any other therapeutic clinical trial.
• Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, ECG findings, or laboratory abnormality that, in the Investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow up would be completed, or could impair the assessment of study results.

Sponsors & Collaborators

• PTC Therapeutics: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (31)

University of Alabama-Birmingham

Birmingham, Alabama, 35233, United States

Location

Miller Children's Hospital Long Beach

Long Beach, California, 90806, United States

Location

Lucile Packard Children's Hospital

Palo Alto, California, 94304, United States

Location

The Children's Hospital

Aurora, Colorado, 80045, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Emory University Cystic Fibrosis Center

Atlanta, Georgia, 30322, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Johns Hopkins Children's Center

Baltimore, Maryland, 21287, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

St. Vincent's Hospital

New York, New York, 10011, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Rainbow Babies & Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Childrens Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Hôpital Erasme

Brussels, Belgium

Location

Hôpital Universitaire des Enfants Reine Fabiola

Brussels, Belgium

Location

University Hospital Brussels

Brussels, Belgium

Location

University Hospital Leuven

Leuven, Belgium

Location

University of Toronto

Toronto, Canada

Location

Hôpital Cochin

Paris, France

Location

Hôpital Necker - Enfants Malades

Paris, France

Location

Hôpital des Enfants

Toulouse, 31059, France

Location

Klinikum der Universität Köln

Cologne, Germany

Location

Hadassah University Hospital - Mount Scopus

Jerusalem, 91240, Israel

Location

Università La Sapienza

Roma, Italy

Location

Azienda Ospedaliera di Verona

Verona, Italy

Location

Universitair Medisch Centrum Utrecht

Utrecht, Netherlands

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Karolinska University Hospital, Huddinge

Stockholm, Sweden

Location

Belfast City Hospital

Belfast, United Kingdom

Location

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

Results Point of Contact

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

medinfo@ptcbio.com

1-866-562-4620

Study Officials

• Temitayo Ajayi, 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: NON RANDOMIZED
• Masking: NONE
• Masking Details: This extension study was not blinded. The investigators and participants remained blinded to the Study 009 treatment assignments throughout participation in Study PTC124-GD-009e-CF.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2010
• First Posted: June 9, 2010
• Study Start: August 12, 2010
• Primary Completion: December 2, 2013
• Study Completion: December 2, 2013
• Last Updated: October 19, 2020
• Results First Posted: October 19, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); IT (2); CA (1); FR (3); IL (1); US (15); NL (1); SE (1); DE (1); BE (4); ES (1)