Study of Ataluren (PTC124™) in Cystic Fibrosis
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: Ataluren; Placebo
Intervention description: Ataluren will be provided as a vanilla-flavored powder to be mixed with water.; Placebo matching to ataluren will be provided.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 238.0
Sex: All
Minimum age: 6 Years
Healthy volunteers: No
Keywords: Cystic fibrosis; Nonsense mutation; Premature stop codon; PTC124; Ataluren; PTC Therapeutics

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 trial that will evaluate the clinical benefit of ataluren in adult
      and pediatric participants with CF due to a nonsense mutation. The main goals of the study
      are to understand whether ataluren can improve pulmonary function and whether the drug can
      safely be given for a long period of time. The study will also assess the effects of ataluren
      on CF pulmonary exacerbation frequency, cough frequency, health-related quality of life,
      antibiotic use for CF-related infections, CF-related disruptions to daily living, body
      weight, and CF pathophysiology.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ability to provide written informed consent (parental/guardian consent and participant
             assent if <18 years of age)

          -  Age ≥6 years

          -  Body weight ≥16 kg

          -  Abnormal nasal transepithelial potential difference (TEPD) total chloride conductance
             (a less electrically negative value than -5 millivolts (mV) for total chloride
             conductance [Δchloride-free+isoproterenol])

          -  Sweat chloride >40 milliequivalents/liter (mEq/L)

          -  Documentation of the simultaneous presence of a nonsense mutation in at least 1 allele
             of the CFTR gene and a CF-causing mutation in the other CFTR allele, as determined by
             gene sequencing from a laboratory certified by the College of American Pathologists
             (CAP), under the Clinical Laboratory Improvement Act/Amendment (CLIA), or by an
             equivalent organization

          -  Verification that a blood sample has been drawn for confirmation of the presence of a
             nonsense mutation in 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 for age, gender,
             and height

          -  Resting oxygen saturation (as measured by pulse oximetry) ≥92% on room air

          -  Documentation by VivoMetrics that the participant has satisfactorily completed a
             24-hour LifeShirt® cough frequency assessment

          -  Confirmed screening laboratory values within the central laboratory ranges (hepatic,
             adrenal, renal, serum electrolytes, and reproduction [women only] parameters)

          -  In 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 4-week follow-up period

          -  Willingness and ability to comply with scheduled visits, drug administration plan,
             study restrictions, and study procedures

        Exclusion Criteria:

          -  Known hypersensitivity to any of the ingredients or excipients of the study drug

          -  Any change (initiation, change in type of drug, dose modification, schedule
             modification, interruption, discontinuation, or reinitiation) in a chronic
             treatment/prophylaxis regimen for CF or for CF-related conditions within 4 weeks prior
             to start of study treatment

          -  Exposure to another investigational drug within 4 weeks prior to start of study
             treatment

          -  Treatment with systemic aminoglycoside antibiotics at the time of the Baseline TEPD
             assessment

          -  Treatment with intravenous antibiotics within 3 weeks prior to start of study
             treatment

          -  History of solid organ or hematological transplantation

          -  Ongoing immunosuppressive therapy (other than corticosteroids)

          -  Ongoing warfarin, phenytoin, or tolbutamide therapy

          -  Ongoing participation in any other therapeutic clinical trial

          -  Major complications of lung disease (including massive hemoptysis, pneumothorax, or
             pleural effusion) within 8 weeks prior to start of study treatment

          -  Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection
             (including viral illnesses) within 3 weeks prior to randomization

          -  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 *
             number of years smoked)

          -  Prior or ongoing medical condition (for example, concomitant illness, alcoholism, drug
             abuse, psychiatric condition), medical history, physical findings, electrocardiography
             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.