A Phase 3, Open-label, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation

Study ID
STU 072015-018

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • CTRC Outpatient
  • Children’s Medical Center (Dallas, Plano, Southlake)
  • Clements University Hospital
  • UT Southwestern Ambulatory Services

Contact
Ashley Keller
214/648-2817
ASHLEY.KELLER@UTSouthwestern.edu

Principal Investigator
Raksha Jain, M.D.

Summary

This is a Phase 3, multicenter, open-label, rollover study in subjects with CF who are
homozygous or heterozygous for the F508del-CFTR mutation and who participated in
Studies 103, 106, 107, 108, 109, or 111. The study is designed to evaluate the safety and
efficacy of long-term treatment of VX-661 in combination with ivacaftor.
a schematic of the study design is shown in Figure 8-1 in the protocol.

This study consists of a Treatment Cohort (eligible subjects 12 years of age and older) and an
observational Cohort (eligible subjects [Less Than]18 years of age [age on the date of informed
consent/assent in the parent study]), which will enroll subjects from Studies 103, 106, 107,
108, 109, and 111. The Treatment Cohort and the observational Cohort will be open to
enrollment in parallel.

Treatment Cohort
Subjects who completed study drug treatment (i.e., VX-661/ivacaftor, ivacaftor
monotherapy, or placebo) during the Treatment Period in the parent study who meet the
eligibility criteria (Sections 9.1 and 9.2 in the protocol) will be offered the opportunity to enroll in
Study 110. Subjects who permanently discontinue study drug treatment or who withdrew
consent during the parent study are not eligible for enrollment in the Treatment Cohort.

The Treatment Cohort will be open-label, and all subjects will receive VX-661 100 mg/
ivacaftor 150-mg fixed-dose combination (FDC) tablet daily (qd) in the morning and
ivacaftor 150-mg tablet qd in the evening. The Treatment Period will be approximately
96 weeks.

During the course of study conduct, if VX-661 in combination with ivacaftor is approved and
available for the treatment of CF in populations enrolled in Study 110, subjects with the
approved CFTR genotypes may be discontinued from this rollover study at the discretion of
the sponsor (Section 10.6 in the protocol). if a subject is continuing onto commercially available
VX-661/ivacaftor, the early Treatment Termination Visit (Section 8.1.1.3 in the protocol) will be completed
before dosing with commercial drug begins, and the Safety Follow-up Visit (Section 8.1.1.2 in the protocol)
will not be required. alternatively, if local health authorities decline to approve, or if clinical
benefit is not demonstrated for the use of VX-661 in combination with ivacaftor for the
treatment of CF in populations enrolled in Study 110, subjects with the relevant CFTR
genotypes may be discontinued after communication to investigators and iRBs/ieCs of the
risks/benefits related to the safety and efficacy observed for the subset of subjects. if subjects
are discontinued from the study, an early Treatment Termination Visit should occur within
7 days of the last dose of study drug and a Safety Follow-up Visit should occur within 28
((+-) 7) days after the last dose of study drug.

observational Cohort
Subjects [Less Than]18 years of age (age on the date of informed consent/assent in the parent study)
who received at least 4 weeks of study drug in the parent study, who are not eligible for the
Treatment Cohort or who elect not to enroll in the Treatment Cohort, and meet eligibility
criteria (Section 9.1 in the protocol) will be offered the opportunity to enroll in the observational Cohort.
Subjects in the observational Cohort will not receive study drug and will have regularly
scheduled telephone calls for approximately 2 years after their last dose of study drug in the
parent study to assess post-treatment safety of VX-661/ivacaftor combination therapy.

Figure 8-1 Study Design in the protocol.

Participant Eligibility

Subjects who meet all of the following inclusion criteria will be eligible for this study.

1. Signed and dated an informed consent form (ICF), and where appropriate, signed and
dated an assent form.
2. Did not withdraw consent from the parent study
3. Able to understand and comply with protocol requirements, restrictions, and instructions,
and likely to complete the study as planned, as judged by the investigator and Vertex,
based in part on study compliance in Studies 103, 106, 107, 108, 109, or 111.
4. The following criteria apply to the Treatment and Observational Cohorts:


* Subjects entering the Treatment Cohort must meet all of the following criteria:
1. Elect to enroll in the Treatment Cohort
2. Completed study drug treatment during the Treatment Period in a parent study
(Studies 103 [Placebo-Controlled Phase or Open-Label Extension Phase], 106,
107, 108, or 109) or study drug treatment and the Safety Follow-up Visit for
subjects from Study 111


* Subjects who had study drug interruptions, but completed study visits up
to the last scheduled visit of the Treatment Period of the parent study (and
the Safety Follow-up Visit for subjects from Study 111) are eligible.


* Subjects who had a study drug interruption at the last scheduled visit of
the Treatment Period of the parent study, subjects who required
interruption to be continued or initiated at Day 1 in Study 110, or subjects
who resumed study drug in the parent study after a study drug interruption
due to elevated transaminases but who did not complete at least 4 weeks
of rechallenge with study drug (due to the timing of the rechallenge versus
the time remaining in the Treatment Period of the parent study) must meet
eligibility criteria and have received approval from the Vertex medical
monitor in order to be enrolled into the Study 110 Treatment Cohort.

Note: Subjects who permanently discontinue study drug treatment during the
parent study, including at the last visit of the Treatment Period, are not
eligible to enroll into the Treatment Cohort.

3. Willing to remain on a stable CF medication (and supplement) regimen
through the Safety Follow-up Visit.


* Subjects entering the Observational Cohort must meet the following criteria:
o <18 years of age (age on the date of informed consent/assent in the parent study)
o Completed study drug treatment during the Treatment Period in a parent study
(Studies 103 [Placebo-Controlled Phase or Open-Label Extension Phase], 106,
107, 108, or 109) or study drug treatment and the Safety Follow-up Visit for
subjects from Study 111, but do not elect to enroll in the Study 110 Treatment
Cohort; or
o Received at least 4 weeks of study drug treatment and completed visits up to the
last scheduled visit of the Treatment Period of a parent study (and the Safety
Follow-up Visit for subjects from Study 111), but do not meet eligibility criteria
for enrollment into the Treatment Cohort

Note: Subjects who permanently discontinued study drug in the parent study must have
completed the last scheduled study visit of the Treatment Period (and the Safety
Follow-up Visit for subjects from Study 111).