Two phase 3, randomized, double blind, placebo controlled, parallel group studies to evaluate the efficacy and safety of lumacaftor in combination with ivacaftor in subjects aged 12 years and older with cystic fibrosis, homozygous for the F508del CFTR mutation
These two phase 3 trials (NCT01807923 and NCT01807949) with the same design were conducted in 96 and 91 sites, respectively across 14 countries (Australia, Belgium, Canada, Czech Republic, Denmark, France, Germany, Ireland, Italy, the Netherlands, Spain, Sweden, UK and USA) to evaluate the efficacy and safety of lumacaftor in combination with ivacaftor in subjects aged 12 years and older with cystic fibrosis, homozygous for the F508del CFTR mutation. A total of 1122 CF patients (≥ 12 years-old) homozygous for the F508del-CFTR mutation were enrolled in these 2 double-blind, placebo-controlled studies to receive lumacaftor (400 q12h or 600 mg once daily (qd)) in combination with ivacaftor (250 mg q12h) or placebo for 24 months. The results were similar in both studies and showed that there was a significant increase in percent predicted FEV1 within 2 weeks of initiating lumacaftor and ivacaftor combination therapy that persisted throughout the study. The treatment difference versus placebo in mean relative change from baseline in percent predicted FEV1 was 5.6% for lumacaftor 600 mg qd + ivacaftor 250 mg q12h (P<0.0001) and 4.8% for lumacaftor 400 mg q12h + ivacaftor 250 q12h (P<0.0001). The combination therapy resulted in a statistically significant reduction of 30% to 39% in the rate of exacerbations versus placebo. CFQ-R and BMI were also improved. Treatment with both doses of lumacaftor and ivacaftor was generally well tolerated. In conclusion, these data suggest that combination of lumacaftor and ivacaftor may benefit patients with CF homozygous for the F508del mutation, the most common CF-causing mutation.
33 ECFS-CTN sites in Belgium, Czech Republic, Denmark, France, Germany, Italy, the Netherlands, Spain, Sweden and UK participated in this study and enrolled 230 of the patients.
The summary of data provided here are from the presentation of the study results at the North American Cystic Fibrosis Conference in Atlanta (GA, USA) in October 2014.