A Study to Evaluate the Safety and Efficacy of Long Term Treatment With VX-661 in Combination With Ivacaftor in Participants With Cystic Fibrosis Who Have an F508del-CFTR Mutation

Vertex Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Cystic Fibrosis

Treatments: Drug: TEZ/IVA; Drug: IVA

Study type: Interventional

Funder types: Industry

Identifiers

NCT02565914

VX14-661-110

2014-004827-29 (EudraCT Number)

Details and patient eligibility

About

This is a Phase 3, multicenter, open-label, 3-part rollover study in subjects with CF who are homozygous or heterozygous for the F508del-CFTR mutation and who participated in studies VX13-661-103 (Study 103, NCT02070744), VX14-661-106 (Study 106, NCT02347657), VX14-661-107 (Study 107, NCT02516410), VX14-661-108 (Study 108, NCT02392234), VX14-661-109 (Study 109, NCT02412111), VX14-661-111 (Study 111, NCT02508207), VX15-661-112 (NCT02730208), and VX16-661-114 (NCT03150719). The study is designed to evaluate the safety and efficacy of long-term treatment of VX-661 in combination with ivacaftor.

Enrollment: 1,131 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Part A:

• Participants entering the Treatment Cohort must meet all of the following criteria:

• Elect to enroll in the Treatment Cohort

• Completed study drug Treatment Period in a parent study (NCT02070744, NCT02347657, NCT02516410, NCT02392234, NCT02412111) or study drug treatment and the Safety Follow up Visit for participants from NCT02508207.

• Willing to remain on a stable CF regimen through the Safety Follow-up Visit.

• Participants re-enrolling in the Part A Treatment Cohort must meet all of the following criteria:

  • Previously received at least 4 weeks of study drug before discontinuing in Part A of Study NCT02565914 to participate in another qualified Vertex study.
  • Completed the last required visit of another qualified Vertex study before or during the Returning Visit in Part A Study NCT02565914.

• Participants entering the Part A Observational Cohort must meet the following criteria:

  • <18 years of age (age on the date of informed consent/assent in the parent study)
  • Completed study drug Treatment Period in a parent study or study drug treatment and the Safety Follow up Visit for subjects from NCT02508207, but do not elect to enroll in the NCT02565914 Treatment Cohort; or
  • 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 participants from NCT02508207), but do not meet eligibility criteria for enrollment into the Treatment Cohort

Part B:

Participants who meet all of the following inclusion criteria will be eligible for Part B.

• Did not withdraw consent from the parent study or Part A of Study NCT02565914.
• Completed study drug treatment during the Treatment Period in Part A of - Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit of Study NCT02565914.

Participants re enrolling in Part B must meet all of the following criteria:

• Previously received at least 4 weeks of study drug before discontinuing Study NCT02565914 to participate in another qualified Vertex study, which is defined as a Vertex study of investigational CFTR modulators that allows participation of participants in Study NCT02565914.
• Completed the last required visit of another qualified Vertex study before or during the Returning Visit in Part B.
• Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit in Part B.

Part C:

• Participants who meet all of the following inclusion criteria will be eligible for Part C.
• Did not withdraw consent from Part B of Study NCT02565914.
• Completed study drug treatment during Part B of NCT02565914.
• Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit of Part C.

Exclusion criteria

• History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the subject.
• Pregnant and nursing females.
• Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements.
• History of drug intolerance in the parent study that would pose an additional risk to the subject.
• Participation in an investigational drug trial (including studies investigating VX-661/ivacaftor or lumacaftor/ivacaftor) other than the parent studies of NCT02565914 or other eligible Vertex studies investigating VX-661 in combination with ivacaftor, or use of a commercially available CFTR modulator.

Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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1,131 participants in 1 patient group

TEZ/IVA

Experimental group

Description:

Part A: Participants who received either TEZ/IVA, IVA monotherapy or Placebo in parent studies 103,106,107,108,109 and 111 were administered TEZ 100 milligram (mg)/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks. Part B: Participants who received either TEZ/IVA, IVA monotherapy or Placebo in parent studies 106,108,109,112 and 114 were administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks. Part C: Participants who received TEZ/IVA, IVA monotherapy or Placebo in parent studies 106,108, and 114 were administered TEZ 100 mg/IVA 150 mg fixed dose tablet in the morning and IVA 150 mg mono tablet in the evening for 192 weeks.

Treatment:

Drug: TEZ/IVA

Drug: IVA