A Phase 2a, Randomized, Double-blind, Placebo-controlled, Incomplete Block, Crossover Study to Evaluate the Safety and Efficacy of VX-371 in Subjects Aged 12 Years or Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation, and Being Treated With Orkambi
- CTRC Outpatient
- Children’s Medical Center (Dallas, Plano, Southlake)
- Clements University Hospital
- UT Southwestern Ambulatory Services
Raksha Jain, M.D.
This is a Phase 2a, randomized, double-blind, placebo-controlled, incomplete block, crossover, multicenter, study in subjects [GreaterThanorequalTo]12 years of age with CF who are homozygous for the F508del-CFTR mutation and who are being treated with orkambi. all subjects must be receiving stable treatment with orkambi before the first dose of study drug and throughout the duration of the study. approximately 150 subjects will be randomized to 1 of the 4 treatment sequences.
Sequence 1) Treatment 1[?] VX-371 + 4.2% HS [and] #9674; Washout [and] #9674; Treatment 2 [?]4.2% HS
2) Treatment 1 [?] 4.2% HS [and] #9674; Washout [and] #9674; Treatment 2 [?] VX-371 + 4.2% HS
3) Treatment 1 [?] VX-371 + 0.17% saline (placebo) [and] #9674; Washout [and] #9674; Treatment 2[?] Placebo (0.17% saline)
4) Treatment 1 [?] Placebo (0.17% saline) [and] #9674; Washout [and] #9674; Treatment 2[?] VX-371 + 0.17% saline (placebo)
This study includes the following periods:
Screening Period: Day -28 to Day -1 relative to the first dose of study drug for orkambi+/HS- subjects. Day -56 to Day -29 relative to the first dose of study drug for orkambi-/HS-, orkambi-/HS+, and orkambi+/HS+ subjects only. all subjects will complete the Screening Visit. Screening will occur between Day -28 and Day -1 for orkambi+/HS- subjects, and between Day -56 and Day -29 for orkambi-/HS-, orkambi-/HS+, and orkambi+/HS+ subjects. Screening will occur before the first dose of study drug to confirm that subjects meet the selection criteria for the study. To prepare for study participation, subjects will be instructed on the study restrictions and use of concomitant. Repetition of Screening assessment(s): Repetition of individual screening assessment(s) that did not meet eligibility criteria is not permitted with the following exceptions:
Rescreening: Subjects may be rescreened after discussion with, and approval from, the Vertex medical monitor or authorized designee.
Run-in Period: Day -28 to Day -1 relative to the first dose of study drug (for orkambi-/HS-, orkambi-/HS+, and orkambi+/HS+ subjects only)
Treatment Period 1: Day 1 (first dose of study drug) through Day 28. The first dose of study drug will be administered after randomization on Treatment Period 1 Day 1. Study drug should be taken according to instructions provided. Study visits will occur on Day 1, Day 14, and Day 28. The last dose of study drug in Treatment Period 1 is the dose of study drug at the Day 28 Visit.
Washout Period: Day 29 through Day 56. Subjects will undergo a Washout Period of 28 days (+ 3 days) between the 2 Treatment Periods and must have at least 14 days in their [Quote]off-period[Quote] for inhaled single cycled antibiotics or at least 14 days of the [Quote]alternate[Quote] antibiotic for a continuous cycled 2 antibiotic regimen.
Treatment Period 2: Day 57 through Day 84. The first dose of study drug in Treatment Period 2 will be administered at the Day 57 Visit. Study visits will occur on Day 57, Day 70, and Day 84. on Day 59, subjects will have a telephone contact for safety purposes (e.g., inquire about adverse events).
Safety Follow-up Telephone Contact: (28 days [+ 3 days] after the last dose of study drug for subjects who complete the Day 84 Visit). For subjects who prematurely discontinue study drug treatment (which is to occur 28 days (+ 3 days) after their last dose of study drug). a Safety Follow-up Telephone Contact is scheduled to occur 28 days (+3 days) after the Day 84 Visit for subjects who complete this visit. The Telephone Contact is a phone interview for the purpose of collecting information on aes. a Safety Follow-up Visit will only be required if a clinical finding during the Treatment Period or during the 28-day. Safety Follow-up Period requires follow-up.
early Termination of Treatment Visit: (which is to occur as soon as possible after the subject decides to terminate study drug treatment)
Subjects who meet all of the following inclusion criteria will be eligible.
1. Subject (or subject[Single Quote]s legally appointed and authorized representative) will sign and date an
informed consent form (ICF) and, where appropriate, assent form.
2. Willing and able to comply with scheduled visits, treatment plan, study restrictions,
laboratory tests, contraceptive guidelines, and other study procedures.
3. Willing and able to use the nebulization device as directed by the study manual.
4. Subjects (male and female) will be aged 12 years or older on the date of ICF or, where
appropriate, date of assent.
5. Subjects with confirmed diagnosis of CF, defined as a sweat chloride value >=60 mmol/L by
quantitative pilocarpine iontophoresis. A sweat chloride test must be performed at the
Screening Visit if an eligible sweat chloride value is not available in the subject[Single Quote]s medical
records and the Screening Visit value is needed to establish eligibility. For subjects using
sweat chloride values documented in their medical records to establish eligibility, the sweat
chloride test at the Screening Visit is optional. If both results are available, the result from the
Screening Visit will be used to determine eligibility.
6. Subjects who are homozygous for F508del-CFTR. If the CFTR screening genotype result is
not received before randomization, a previous CFTR genotype lab report may be used to
establish eligibility. Note: Subjects who have been randomized and whose screening
genotype does not confirm study eligibility must be discontinued from the study as described
in Section 9.5 of the protocol.
7. Subjects with ppFEV1 of >=40 to <90 percentage points adjusted for age, sex, and height
according to the Global Lung Initiative (GLI) at the Screening Visit.
8. Subjects with stable CF disease as deemed by the investigator.
9. Subjects who are willing to remain on a stable CF medication regimen through the Safety
Follow-up Telephone Contact.
10. Subjects who are willing to discontinue physician-prescribed HS use.
11. Female subjects of childbearing potential must have a negative serum pregnancy test at the
Screening Visit. Females of childbearing potential must have a negative urine pregnancy test
at the Day 1 Visit before receiving the first dose of inhaled study drug.
12. Subjects of childbearing potential and who are sexually active must meet the contraception
requirements outlined in Section 126.96.36.199 of the protocol.