Clinical trial NCT01531673: Study of VX-661 Alone and in Combination With Ivacaftor in Subjects Homozygous or Heterozygous to the F508del-Cystic Fibrosis Transmembrane Conductance Regulator(CFTR) Mutation
Official title: A Phase 2, Multicenter, Double-Blinded, Placebo Controlled Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-661 Monotherapy and VX-661/Ivacaftor Cotherapy in Subjects With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2012-02-13
Enrollment: 194
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: The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) effects of VX-661 alone and when coadministered with ivacaftor in participants with cystic fibrosis (CF) who are homozygous or heterozygous for the F508del-CFTR mutation.

Detailed description: This is a Phase 2, randomized, multicenter, double-blinded, placebo-controlled, study of VX-661 monotherapy, and VX-661/ivacaftor co-therapy in participants with CF who are homozygous or heterozygous for the F508del CFTR mutation.

This study is separated into seven groups: Group 1-7, respectively. Approximately 180 participants were randomized in a ratio of 4:1; active drug to matching placebo in each group.

Eligibility criteria: Inclusion Criteria:

* Male or female with confirmed diagnosis of CF
* Must have the F508del-CFTR gene mutation in both alleles (Groups 1, 2, 3, 4, 5, 6). Group 7 participants must have the F508del-CFTR mutation on 1 allele, and gating mutation G551D on the second allele and have been on their physician prescribed 150 mg KalydecoTM q12h (commercially available ivacaftor) for at least 28 days at the Screening Visit.
* Forced expiratory volume in 1 second(FEV1) 40% to 90% (inclusive) of predicted normal for age, gender, and height (Knudson standards) at screening
* Weight \>40 kg and BMI \>18.5
* Participants of child-bearing potential and who are sexually active must meet the contraception requirements.

Exclusion Criteria:

* History of any illness 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 4 weeks before Study Day 1.
* History of solid organ or hematological transplantation
* Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer) before screening
* History of alcohol, medication, or illicit drug abuse within 1 year prior to screening
* Pregnant, breast-feeding, or not willing to follow contraception requirements

Primary outcomes:
measure: Safety as Determined by Adverse Events (AEs)
timeFrame: Start of study drug through the Follow-up Visit (Up to Day 56)
measure: Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b
timeFrame: Baseline through Day 28
measure: Change in Sweat Chloride From Baseline Through Study Day 28 for Group 6
timeFrame: Baseline through Day 28
measure: Change in Sweat Chloride From Baseline Through Study Day 28 for Group 7
timeFrame: Baseline through Day 28
Secondary outcomes:
measure: Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b
timeFrame: Baseline, Day 7, Day 14, Day 21, Day 28
measure: Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6
timeFrame: Baseline, Day 7, Day 14, Day 21, Day 28
measure: Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7
timeFrame: Baseline, Day 7, Day 14, Day 21, Day 28
measure: Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b
timeFrame: Baseline, Day 7, Day 14, Day 21, Day 28
measure: Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6
timeFrame: Baseline, Day 7, Day 14, Day 21, Day 28
measure: Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7
timeFrame: Baseline, Day 7, Day 14, Day 21, Day 28
measure: Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b
timeFrame: Baseline, Day 7, Day 14, Day 21, Day 28
measure: Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6
timeFrame: Baseline, Day 7, Day 14, Day 21, Day 28
measure: Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7
timeFrame: Baseline, Day 7, Day 14, Day 21, Day 28
measure: Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b
timeFrame: Baseline, Day 14, Day 28
measure: Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6
timeFrame: Baseline, Day 14, Day 28
measure: Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7
timeFrame: Baseline, Day 14, Day 28
measure: Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 After Administration of VX-661 Monotherapy
timeFrame: Day 28
measure: AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor
timeFrame: Day 28
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Vertex Investigational Site
state: Alabama
city: Oakland
country: United States
facility: Vertex Investigational Site
state: California
city: Boise
country: United States
facility: Vertex Investigational Site
state: Idaho
city: Chicago
country: United States
facility: Vertex Investigational Site
state: Illinois
city: Boston
country: United States
facility: Vertex Investigational Site
state: Massachusetts
city: Grand Rapids
country: United States
facility: Vertex Investigational Site
state: Michigan
city: Kansas City
country: United States
facility: Vertex Investigational Site
state: Missouri
city: Long Branch
country: United States
facility: Vertex Investigational Site
state: New Jersey
city: New Hyde Park
country: United States
facility: Vertex Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: Vertex Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Vertex Investigational Site
state: Ohio
city: Columbus
country: United States
facility: Vertex Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Vertex Investigational Site
state: Oklahoma
city: Hershey
country: United States
facility: Vertex Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Vertex Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: Vertex Investigational Site
state: South Carolina
city: Salt Lake City
country: United States
facility: Vertex Investigational Site
state: Utah
city: Burlington
country: United States
facility: Vertex Investigational Site
state: Vermont
city: Seattle
country: United States
facility: Vertex Investigational Site
state: Washington
city: Calgary
country: Canada
facility: Vertex Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: Vertex Investigational Site
state: British Columbia
city: Halifax
country: Canada
facility: Vertex Investigational Site
state: Nova Scotia
city: Toronto
country: Canada
facility: Vertex Investigational Site
state: Ontario
city: Erlangen
country: Germany
facility: Vertex Investigational Site
state: Bayern
city: Frankfurt
country: Germany
facility: Vertex Investigational Site
state: Hessen
city: Hannover
country: Germany
facility: Vertex Investigational Site
state: Niedersachsen
city: Koeln
country: Germany
facility: Vertex Investigational Site
state: Nordrhein Westfalen
city: Berlin
country: Germany
facility: Vertex Investigational Site
city: Bochum
country: Germany
facility: Vertex Investigational Site
city: Jena
country: Germany
facility: Vertex Investigational Site
city: Munich
country: Germany
facility: Vertex Investigational Site
city: Cambridge
country: United Kingdom
facility: Vertex Investigational Site
state: Cambridgeshire
city: London
country: United Kingdom
facility: Vertex Investigational Site
state: Greater London
city: Manchester
country: United Kingdom
facility: Vertex Investigational Site
state: Greater Manchester
city: Southhampton
country: United Kingdom
facility: Vertex Investigational Site
state: Hampshire
city: Cardiff
country: United Kingdom
facility: Vertex Investigational Site
state: Vale Of Glamorgen
Study officials:
affiliation: University of North Carolina
name: Scott Donaldson, MD
role: PRINCIPAL_INVESTIGATOR
References: