Study of Ataluren in Nonsense Mutation Cystic Fibrosis (ACT CF)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02139306
• Date of registration: 13/05/2014
• Prospective Registration: Yes
• Primary sponsor: PTC Therapeutics
• Public title: Study of Ataluren in Nonsense Mutation Cystic Fibrosis (ACT CF)
• Scientific title: A Phase 3 Efficacy and Safety Study of Ataluren (PTC124®) in Patients With Nonsense Mutation Cystic Fibrosis
• Date of first enrolment: August 2014
• Target sample size: 279
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02139306
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

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

Contacts

• Name: Joseph McIntosh, MD
• Affiliation: PTC Therapeutics

Key inclusion & exclusion criteria

Inclusion Criteria:

- Evidence of signed and dated informed consent/assent document(s) indicating that the
subject (and/or his parent/legal guardian) has been informed of all pertinent aspects
of the trial

- Age >=6 years.

- Body weight >=16 kg.

- Sweat chloride >60 milliequivalent per liter (mEq/L)

- Documentation of the presence of a nonsense mutation in at least 1 allele of the
cystic fibrosis transmembrane conductance regulator (CFTR) gene, as determined by
genotyping performed at a laboratory certified by the College of American Pathologists
(CAP), or under the Clinical Laboratory Improvement Act/Amendment (CLIA), or by an
equivalent organization

- Verification that a blood sample has been drawn for sequencing of the CFTR gene

- Ability to perform a valid, reproducible spirometry test using the study-specific
spirometer with demonstration of an FEV1 >=40% and <=90% of predicted

- Demonstration at Visit 2 of a valid %-predicted FEV1 within 15% of the Screening %
predicted FEV1 value

- Resting oxygen saturation (as measured by pulse oximetry) >=92% on room air.

- Confirmed screening laboratory values within pre-specified ranges

- In subjects 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, study procedures, laboratory tests, and
study restrictions

Exclusion Criteria:

- Known hypersensitivity to any of the ingredients or excipients of the study drug

- Previous participation in the Phase 3 trial of ataluren (PTC124-GD-009-CF).

- Any change (initiation, change in type of drug, dose modification, schedule
modification, interruption, discontinuation, or re-initiation) in a chronic
treatment/prophylaxis regimen for Cystic Fibrosis (CF) or for CF-related conditions
within 4 weeks prior to screening

- Chronic use of inhaled aminoglycosides (eg, tobramycin) or use of inhaled
aminoglycosides within 4 weeks prior to screening.

- Exposure to another investigational drug within 4 weeks prior to screening

- Ongoing participation in any other therapeutic clinical trial

- Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection
(including viral illnesses) within 3 weeks prior to screening

- Treatment with intravenous antibiotics within 3 weeks prior to screening

- Ongoing immunosuppressive therapy (other than corticosteroids)

- Ongoing warfarin, phenytoin, or tolbutamide therapy

- History of solid organ or hematological transplantation

- Major complications of lung disease (including massive hemoptysis, pneumothorax, or
pleural effusion) within 8 weeks prior to screening

- Known portal hypertension

- Positive hepatitis B surface antigen, hepatitis C antibody test, or human
immunodeficiency virus (HIV) test

- Pregnancy or breast-feeding

- Current smoker or a smoking history of >=10 pack-years (number of cigarette packs/day
x number of years smoked).

- Prior or ongoing medical condition (eg, concomitant illness, alcoholism, drug abuse,
psychiatric condition), medical history, physical findings, electrocardiogram (ECG)
findings, or laboratory abnormality that, in the investigator's opinion, could
adversely affect the safety of the subject, makes it unlikely that the course of
treatment or follow-up would be completed, or could impair the assessment of study
results



Age minimum: 6 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: Ataluren (PTC124®)

Drug: Placebo

Primary Outcome(s)

Absolute Change From Baseline in Percent-predicted Forced Expiratory Volume in One Second (ppFEV1) at Week 48 [Time Frame: From Baseline to Week 48]

Secondary Outcome(s)

Number of Participants With SAEs by Severity and Relationship to Study Drugs [Time Frame: From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)]

Change From Baseline in the Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Domain at Week 48 [Time Frame: Baseline (Day 1) and Week 48]

Number of Participants With Abnormal Electrocardiogram Reported as TEAEs [Time Frame: From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)]

Change From Baseline in Body Mass Index (BMI) at Week 48 [Time Frame: Baseline (Day 1) and Week 48]

48-week Rate of Pulmonary Exacerbations [Time Frame: Week 48]

Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs [Time Frame: From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)]

Number of Participants With Abnormal Vital Signs Reported as TEAEs [Time Frame: From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)]

Number of Participants With TEAEs by Severity and Relationship to Study Drugs [Time Frame: From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)]

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) [Time Frame: From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)]

Secondary ID(s)

2013-004581-34

PTC124-GD-021-CF

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Cystic Fibrosis Foundation

ECFS-Clinical Trial Network (ECFS-CTN)

Results

• Results available: Yes
• Date Posted: 14/05/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02139306