Clinical Trials

Date: 2017-03-02

Type of information: Results

phase: 3

Announcement: results

Company: PTC Therapeutics (USA - NJ)

Product: Translarna™ (ataluren)

Action mechanism:

• protein restauration therapy/inducer of ribosomal readthrough on nonsense mutation mRNA stop codons. Ataluren (3-[5-(2-fluoro-phenyl)-[1,2,4]oxadiazole-3-yl]-benzoic acid) is an investigational new drug designed to enable the production of functional dystrophin protein in the muscle cells of patients with genetic disorders due to a nonsense mutation. Ataluren is designed to allow the ribosome to ignore the premature stop signal and continue translation of the mRNA, resulting in formation of a functioning protein. Ataluren does not cause the ribosome to read through the normal stop signal.

Disease: nonsense mutation cystic fibrosis (nmCF)

Therapeutic area: Rare diseases - Genetic diseases

Country:

Trial details:

• ACT CF (ataluren confirmatory trial in cystic fibrosis) is an international, randomized, double-blind, placebo-controlled, efficacy and safety study of Translarna™ (ataluren) in patients six years of age or older with nmCF not receiving chronic inhaled aminoglycosides. The primary endpoint is lung function as measured by relative change in percent predicted FEV1. The study is planning to enroll 208 patients. Patients are randomly assigned to one of two treatment arms: Translarna™ (ataluren) three times per day (40-mg/kg/day) or placebo (morning, midday, evening). It is anticipated that participants who have successfully completed this study will have the opportunity to receive Translarna™ (ataluren) in an extension study, except in countries where Translarna™ (ataluren) is commercially available for the treatment of nonsense mutation cystic fibrosis. (NCT02139306)

Latest news:

• • On March 2, 2017, PTC Therapeutics announced that the Ataluren Confirmatory Trial (ACT CF) in nonsense mutation cystic fibrosis (nmCF) did not achieve its primary or secondary endpoints. Ataluren was generally well tolerated and ACT CF confirmed a favorable safety profile for ataluren, which has now been used by more than 1,000 patients across multiple indications. PTC plans to discontinue current clinical development of ataluren in cystic fibrosis, close ongoing extension studies and withdraw its application for marketing authorization in cystic fibrosis in Europe.
• The  study, conducted in 16 countries, enrolled 279 patients who were randomized to receive either ataluren or placebo. In the intent-to-treat population, the primary endpoint of lung function as measured by absolute change in percent-predicted FEV1 (forced expiratory volume in one second), over 48 weeks from baseline, there was a 0.6% difference in favor of ataluren versus placebo (-1.4% change on ataluren versus -2.0% change on placebo; p=0.534). For the secondary endpoint of rate of pulmonary exacerbations, there was a trend in favor of ataluren, with the rate in the ataluren group being 14% lower than the placebo group (p=0.401). The results were not statistically significant.
• • On November 19, 2015, PTC Therapeutics announced that it has completed enrollment of ACT CF, the company's second Phase 3 clinical trial of Translarna™ (ataluren) for patients with nonsense mutation cystic fibrosis. On September 30, 2015, the European Medicines Agency (EMA) validated the submission of a variation for a new indication for Translarna for the treatment of nonsense mutation cystic fibrosis. The company's regulatory application for Translarna  was based on clinical data and analyses generated from the company's previously completed Phase 3 double-blind, placebo-controlled study comparing Translarna to placebo in nmCF patients. ACT CF study has reached full enrollment across 88 sites globally. Patients in the trial are eligible to participate in an open-label extension study, which has already begun enrolling patients who have completed the initial 48 weeks of treatment.
• • On June 30, 2014, PTC Therapeutics announced the initiation of a global confirmatory Phase 3 clinical trial of Translarna™ (ataluren) in patients with nonsense mutation cystic fibrosis (nmCF). Nonsense mutations within cystic fibrosis are categorized as Class I mutations, a severe form of CF that results in little or no production of the CFTR protein. The Phase 3 confirmatory trial is referred to as ACT CF (ataluren confirmatory trial in cystic fibrosis) and the primary endpoint is lung function as measured by relative change in percent predicted forced expiratory volume in one second, or FEV1.

Is general: Yes