PTC124 for Pediatric Patients With Cystic Fibrosis
In some patients with cystic fibrosis (CF), the disease is caused by a nonsense mutation (premature stop codon) in the gene that makes the cystic fibrosis transmembrane regulator (CFTR) protein. PTC124 has been shown to partially restore CFTR production in animals with CF due to a nonsense mutation. The main purpose of this study is to understand whether PTC124 can safely increase functional CFTR protein in the cells of patients with CF due to a nonsense mutation.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of PTC124 as an Oral Treatment for Nonsense-Mutation-Mediated Cystic Fibrosis|
- CFTR activity as assessed by nasal transepithelial difference (TEPD)
- Side effects
- Presence of CFTR protein and mRNA
- Compliance with treatment
- Lung function
- Sputum test
- Sweat test
- Body weight
- PTC124 pharmacokinetics
|Study Start Date:||March 2007|
|Study Completion Date:||March 2008|
|Primary Completion Date:||March 2008 (Final data collection date for primary outcome measure)|
In this study, patients with CF due to a nonsense mutation will be treated with a new investigational drug called PTC124. Evaluation procedures (history, physical examination, blood and urine tests to assess organ function, electrocardiogram (ECG), chest x-ray, and CF-specific tests) to determine if a patient qualifies for the study will be performed within 21 days prior to the start of treatment. Eligible patients with nonsense-mutation-mediated CF will receive two repeated 28-day cycles, each comprising 14 days on therapy and 14 days off therapy. In a crossover design, patients will be randomized to receive PTC124 treatment in Cycle 1 by either of the following regimens:
- PTC124, given 3 times per day (TID) with a regimen of 4 mg/kg at breakfast, 4 mg/kg at lunch, and 8 mg/kg at dinner, or
- PTC124, given 3 times per day (TID) with a regimen of 10 mg/kg at breakfast, 10 mg/kg at lunch and 20 mg/kg at dinner.
In Cycle 2, patients will then receive the drug according to the regimen opposite from that given in Cycle 1.
There will be a 2-night stay at the clinical research center at the beginning and at the end of each 14 days of PTC124 treatment, which means that there will be four 2-night stays at the clinical research center during the study. During the study, PTC124 efficacy, safety, and pharmacokinetics will be evaluated periodically with measurement of transepithelial potential difference (TEPD), nasal mucosal brushing to assess for cellular CFTR mRNA and protein, medical history, physical examinations, blood tests, sputum test, urinalysis, ECGs, chest x-ray, and pulmonary function tests.
|Reine Fabiola Hospital|
|Brussels, Belgium, 1020|
|UZ Gasthuisberg Leuven|
|Leuven, Belgium, 3000|
|Hopital Necker Enfants Malades|
|Paris, France, 75015|
|Principal Investigator:||Isabelle Sermet-Gaudelus, MD||Hopital Necker|