Vertex 809/770 in People with Cystic Fibrosis and F508del-CFTR mutation
Study Type:
Interventional
Intervention Category:
CFTR Modulation
Study Sponsor:
Vertex
Study Phase:
2
Recruitment Status:
Recruiting Completed
Study Drug(s):
VX-809/VX-770
Number of Participants Being Recruited:
160
Single / Multi-Center:
Multi-Center
STUDY BACKGROUND INFORMATION:
This study looked at the safety and effectiveness of the study drug, VX 809 when taken alone and when taken in combination with the study drugn VX 770 in people with CF who have either one or two copies of the delta F508 CFTR gene.
ELIGIBILITY
Age:
>= 18 Years
FEV1:
>= 40 Percent Predicted
P. aeruginosa status:
Not applicable
B. cepacia status:
Not applicable
Other Primary Eligibility Requirements:
To be eligible for this study the participant must be either heterozygous or homozygous with the delta F508 mutation.
Note: Detailed eligibility criteria information may be available on clinicaltrials.gov. If a specific
trial listing for this trial is available, a link to the specific clinicaltrials.gov listing will be present in the "More Information" section below.
FOR MORE INFORMATION:
Sponsor Contact Information:
Medical Monitor, Vertex (617) 444-6777 medicalinfo@vrtx.com
COHORT 1: Sixty-two subjects with CF were enrolled in Cohort 1 of this Phase 2 randomized study to receive 200 mg VX-809 alone or placebo daily for 14 days followed by 7 days of treatment with VX-809 plus VX-770 at either 150 mg or 250 mg or placebo twice daily. The primary endpoints were safety and change in sweat chloride from Day 14 to Day 21.
COHORT 2: Eighty-two participants with CF age 18 and older with 1 (heterozygous) or 2 (homozygous) copies of the F508del mutation were enrolled in Cohort 2 of this study. Participants were divided into five treatment groups. Three groups of homozygous F508 del participants were randomized to receive VX-809 (Lumacaftor) alone (200 mg, 400 mg or 600 mg, once daily) for 28 days and then in combination with ivacaftor (Kalydecoâ?¢) (250 mg, twice daily) for an additional 28 days. One group of heterozygous F508del participants received VX-809 alone (600 mg) for 28 days and then in combination with ivacaftor (250 mg) for an additional 28 days. The placebo group included both homozygous and heterozygous participants. The primary endpoints of the study were safety and change in sweat chloride (pharmacodynamic effect).
Secondary Efficacy:
COHORT 1: The key secondary endpoint was change in FEV1 from Day 14 to Day 21. The VX-770 150 mg group had a significant Day 14 to Day 21 improvement (3.5%) in FEV1; the VX-770 250 mg group did not show improvement. COHORT 2: The key clinical efficacy endpoint was absolute change in FEV1 percent predicted. In the second period there was a statistically significant improvement in lung function (FEV1) in all co-administered dose groups compared to placebo. In the 600 mg VX-809 plus ivacaftor group, a 6.1% within-group and 8.6% treatment effect versus placebo (p<0.001 for both) was observed
Safety:
COHORT 1: From baseline to Day 14, subjects receiving VX-809 alone showed a significant reduction in sweat chloride (-4.2%). In the group receiving VX-809 coadministered with 250 mg of VX-770, there was a significant 2-fold greater reduction in sweat chloride between Day 14 and Day 21 (-9.1%); the VX-770 150 mg group did not show significant change in the same time interval. No clinically important differences were seen between groups in frequency or type of adverse events. COHORT 2: In homozygous patients treated with 600 mg of VX-809 alone for 28 days, there was a statistically significant mean decrease in sweat chloride of- 6.41mmol/L compared to placebo (p=0.012). An additional mean decrease in sweat chloride of -2.82mmol/L was observed with combination treatment between Day 28 and 56, which was not statistically significant. VX-809 was generally well tolerated alone and in combination with ivacaftor. Most adverse events were respiratory, mild to moderate in severity, and similar between treatment and placebo groups. The rate of serious adverse events was also similar between treatment and placebo groups.
COHORT 1: The summary of data provided here is from a poster presented at the Cystic Fibrosis Foundation North American CF Conference (2011). These data may be preliminary and have not been peer-reviewed.
COHORT 2: The summary of data provided here is from a poster presented at the Cystic Fibrosis Foundation North American CF Conference (2012). These data may be preliminary and have not been peer-reviewed.
