A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study 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
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter
study in subjects with CF who are homozygous for the F508del-CFTR mutation. This study
is designed to evaluate the efficacy and safety of lumacaftor in combination with ivacaftor.
This study will evaluate 2 dose levels of lumacaftor in combination with ivacaftor.
This study includes a Screening Period, a Treatment Period, and a Safety Follow-up Visit.
Approximately 501 subjects will be randomized, stratified by age ([AND]amp;lt;18 versus >=18 years of
age), sex (male versus female), and FEV1 severity determined at the Screening Visit
([AND]amp;lt;70% versus >=70% predicted), and then randomized (1:1:1) to 1 of the 3 treatment arms. Efforts will be made to ensure adequate enrollment in each age stratum.
At the Week 24 Visit, subjects who complete the visits in the Treatment Period, regardless of
whether they have prematurely discontinued study drug treatment, will be offered the
opportunity to enroll in a Treatment Cohort or Observational Cohort in a rollover study of
lumacaftor in combination with ivacaftor (VX12-809-105 [Study 105]).
Subjects who meet all of the following inclusion criteria will be eligible for this study:
1. Signed informed consent form (ICF), and where appropriate, signed assent form.
2. Males and females, aged 12 years or older on the date of informed consent or, where
appropriate, date of assent.
3. Confirmed diagnosis of CF defined as:
A sweat chloride value greater than or equel to 60 mmol/L by quantitative pilocarpine iontophoresis
OR 2 CF-causing mutations (all as documented in the subject's medical record) AND
Chronic sinopulmonary disease
OR gastrointestinal/nutritional abnormalities
4. Homozygous for the F508del-CFTR mutation, genotype to be confirmed at Screening.
5. FEV1 >=40% and <=90% of predicted normal for age, sex, and height (Hankinson or Wang
equations) at Screening
6. Stable CF disease as judged by the investigator.
7. Willing to remain on a stable CF medication regimen through Week 24 or, if applicable,
the Safety Follow-up Visit.
8. Able to understand and comply with protocol requirements, restrictions, and instructions
and likely to complete the study as planned (as judged by the investigator)