Clinical trial NCT02516410: A Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation and With a Second CFTR Mutation That Is Not Likely to Respond to VX-661 and/or Ivacaftor Therapy (F508del/NR)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2015-08-05
Enrollment: 168
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study to evaluate the efficacy of VX-661 in combination with ivacaftor (IVA, VX-770) through Week 12 in participants with cystic fibrosis (CF) who are heterozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene and with a second CFTR mutation that is not likely to respond to VX-661 and/or IVA therapy (F508del/not responsive \[NR\]).


Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of CF defined as a sweat chloride value greater than or equal to (\>=)60 millimole per liter (mmol/L) by quantitative pilocarpine iontophoresis.
* Heterozygous for the F508del-CFTR mutation and with a second CFTR mutation that is not likely to respond to VX-661 and/or ivacaftor therapy, genotype to be confirmed via assessment at the Screening Visit.
* Forced Expiratory Volume in 1 Second (FEV1) \>=40 percent (%) and less than or equal to (\<=)90% of predicted normal for age, sex, and height at Screening Visit.

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 in administering study drug to the participant.
* An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug).
* History of solid organ or hematological transplantation.
* Ongoing or prior participation in an investigational drug study or use of commercially available CFTR modulator within 30 days of screening.
* Pregnant or nursing females.

Primary outcomes:
measure: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12
timeFrame: Baseline, Through Week 12
Secondary outcomes:
measure: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12
timeFrame: Baseline, Through Week 12
measure: Number of Pulmonary Exacerbation Events
timeFrame: Baseline through Week 12
measure: Number of Pulmonary Exacerbation Events Per Year
timeFrame: Baseline through Week 12
measure: Absolute Change From Baseline in Body Mass Index (BMI) at Week 12
timeFrame: Baseline, Week 12
measure: Relative Change From Baseline in Percent Predicted FEV1 Through Week 12
timeFrame: Baseline, Through Week 12
measure: Absolute Change From Baseline in Sweat Chloride Through Week 12
timeFrame: Baseline, Through Week 12
measure: Number of Participants With at Least One Pulmonary Exacerbation Through Week 12
timeFrame: Baseline through Week 12
measure: Absolute Change From Baseline in BMI Z-score at Week 12 (in Participants Less Than [<] 20 Years Old at the Time of Screening)
timeFrame: Baseline, Week 12
measure: Absolute Change From Baseline in Body Weight at Week 12
timeFrame: Baseline, Week 12
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 16
measure: Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolite (M1 VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
timeFrame: Pre-morning dose on Week 2, Week 4, Week 8 and Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Miami
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: New Orleans
country: United States
state: Louisiana
city: Ann Arbor
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: New York
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Memphis
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Brisban
country: Australia
state: Queensland
city: Chermside
country: Australia
city: Herston
country: Australia
city: Innsbruck
country: Australia
city: Westmead
country: Australia
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Salzburg
country: Austria
city: Vancouver
country: Canada
state: British Columbia
city: Montreal
country: Canada
city: Bron Cedex
country: France
city: Montpellier Cedex 5
country: France
city: Paris Cedex 14
country: France
city: Paris Cedex 19
country: France
city: Paris
country: France
city: Haifa
country: Israel
city: Hashomer
country: Israel
city: Jerusalem
country: Israel
city: Petah Tikva
country: Israel
city: Barcelona
country: Spain
city: Valencia
country: Spain
Study officials:
References:
citation: Munck A, Kerem E, Ellemunter H, Campbell D, Wang LT, Ahluwalia N, Owen CA, Wainwright C. Tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for minimal function CFTR mutations. J Cyst Fibros. 2020 Nov;19(6):962-968. doi: 10.1016/j.jcf.2020.04.015. Epub 2020 Jun 13.