Clinical trial NCT02347657: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor
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, Homozygous for the F508del CFTR Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Keywords: Homozygous for the F508del CFTR Mutation
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2015-01-27
Enrollment: 510
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: This is a Phase 3, randomized, double blind, placebo controlled, parallel group, multicenter study in people with cystic fibrosis (CF) who are homozygous for the F508del CF transmembrane conductance regulator (CFTR) gene mutation.

Detailed description: This is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study in people with CF who are homozygous for the F508del-CFTR mutation. This study is designed to evaluate the efficacy and safety of VX-661 in combination with Ivacaftor (IVA, VX-770). The active treatment regimen comprised of a morning dose of a fixed-dose combination (FDC) tablet of 100 milligram (mg) VX-661/150 mg IVA once daily (qd) and an evening dose of IVA 150 mg to be taken approximately 12 hours after the morning dose. The placebo regimen was visually matched tablets to be taken with the same schedule as the active treatment.

Eligibility criteria: Inclusion Criteria:

* Homozygous for the F508del CFTR mutation, genotype to be confirmed at the Screening Visit
* Confirmed diagnosis of CF defined as a sweat chloride value ≥60 mmol/L by quantitative pilocarpine iontophoresis
* Forced expiratory volume at one second (FEV1) ≥40% and ≤90% of predicted normal for age, sex, and height during screening
* Stable CF disease as judged by the investigator
* Willing to remain on a stable CF medication regimen through Week 24 or, if applicable, the Safety Follow up 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)
* Pregnant or nursing females (females of childbearing potential must have a negative pregnancy test at Screening and Day 1)
* Sexually active participants of reproductive potential who are not willing to follow the contraception requirements

Primary outcomes:
measure: Absolute Change From Baseline (Day 1) in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24
timeFrame: Day 1, Through Week 24
Secondary outcomes:
measure: Relative Change From Baseline (Day 1) in ppFEV1 Through Week 24
timeFrame: Day 1, Through Week 24
measure: Number of Pulmonary Exacerbations Per Year
timeFrame: Day 1 through Week 24
measure: Absolute Change From Baseline (Day 1) Body Mass Index (BMI) at Week 24
timeFrame: Day 1, Week 24
measure: Absolute Change From Baseline (Day 1) in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24
timeFrame: Day 1, Through Week 24
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Week 28
measure: Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24
timeFrame: Day 1 through Week 24
measure: Absolute Change From Baseline (Day 1) in Sweat Chloride Through Week 24
timeFrame: Day 1, Through Week 24
measure: Absolute Change From Baseline (Day 1) in BMI Z-score at Week 24 in Participants Less Than (<) 20 Years Old at the Time of Screening)
timeFrame: Day 1, Week 24
measure: Absolute Change From Baseline (Day 1) in Body Weight at Week 24
timeFrame: Day 1, Week 24
measure: Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661 and M2-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
timeFrame: Pre-morning dose on Week 16
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Long Beach
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Peoria
country: United States
state: Illinois
city: Boston
country: United States
state: Massachusetts
city: Minneapolis
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Manchester
country: United States
state: New Hampshire
city: Long Branch
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Albany
country: United States
state: New York
city: Buffalo
country: United States
state: New York
city: New Hyde Park
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Akron
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Charleston
country: United States
state: South Carolina
city: Sioux Falls
country: United States
state: South Dakota
city: Fort Worth
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Milwaukee
country: United States
state: Wisconsin
city: Calgary
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Halifax
country: Canada
state: Nova Scotia
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Copenhagen O
country: Denmark
city: Marseille cedex 20
country: France
state: Bouches-du-Rhone
city: Roscoff
country: France
state: Finistere
city: Bordeaux
country: France
state: Girande
city: Lille Cedex
country: France
state: Nord
city: Paris cedex 14
country: France
state: Paris
city: Paris Cedex 19
country: France
state: Paris
city: Pierre Benite cedex
country: France
state: Rhone
city: Heidelberg
country: Germany
state: Baden Wuerttemberg
city: Muenchen
country: Germany
state: Bayern
city: Wuerzburg
country: Germany
state: Bayern
city: Belfast
country: Germany
state: Berlin
city: Frankfurt
country: Germany
state: Hessen
city: Giessen
country: Germany
state: Hessen
city: Berlin
country: Germany
city: Cork
country: Ireland
city: Dublin
country: Ireland
city: Genova
country: Italy
city: Palermo
country: Italy
city: Roma
country: Italy
city: Torino
country: Italy
city: Verona
country: Italy
city: Den Haag
country: Netherlands
city: Groningen
country: Netherlands
city: Nijmegen
country: Netherlands
city: Rotterdam
country: Netherlands
city: Utrecht
country: Netherlands
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Goteborg
country: Sweden
city: Stockholm
country: Sweden
city: Uppsala
country: Sweden
city: Bern
country: Switzerland
city: Zuerich
country: Switzerland
city: Exeter
country: United Kingdom
state: Devon
city: Liverpool
country: United Kingdom
state: Lancashire
city: Sheffield
country: United Kingdom
state: South Yorkshire
city: Newcastle Upon Tyne
country: United Kingdom
state: Tyne & Wear
city: Birmingham
country: United Kingdom
state: West Midlands
city: Belfast
country: United Kingdom
city: London
country: United Kingdom
Study officials:
References:
citation: Taylor-Cousar JL, Munck A, McKone EF, van der Ent CK, Moeller A, Simard C, Wang LT, Ingenito EP, McKee C, Lu Y, Lekstrom-Himes J, Elborn JS. Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del. N Engl J Med. 2017 Nov 23;377(21):2013-2023. doi: 10.1056/NEJMoa1709846. Epub 2017 Nov 3.