Clinical trial NCT02392234: A Phase 3 Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation, and a Second Allele With a CFTR Mutation Predicted to Have Residual Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2015-03-18
Enrollment: 248
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of VX-661 in combination with ivacaftor (IVA, VX-770) and IVA monotherapy in participants with Cystic Fibrosis (CF) who are heterozygous for F508del-CFTR allele and a second allele with a CFTR mutation predicted to have residual function.


Eligibility criteria: Inclusion Criteria:

* Heterozygous for F508del-CFTR and a second allele with a CFTR mutation predicted to have residual function
* Forced Expiratory Volume in 1 Second (FEV1) greater than or equal to (≥) 40 percent (%) and less than or equal to (≤) 90% of predicted normal for age, sex, and height during screening
* Sweat chloride value ≥60 millimole per liter (mmol/L) during screening OR as documented in the participant's medical record
* Stable CF disease as judged by the investigator

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
* History of solid organ or hematological transplantation
* Ongoing or prior participation in an investigational drug study (including studies investigating VX-661, lumacaftor \[VX-809\], and/or ivacaftor) within 30 days of screening
* Pregnant and nursing females
* Sexually active participants of reproductive potential who are not willing to follow the contraception requirements

Primary outcomes:
measure: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Week 4 and Week 8
timeFrame: Baseline, Week 4 and Week 8 of each treatment period
Secondary outcomes:
measure: Absolute Change From Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Week 4 and Week 8
timeFrame: Baseline, Week 4 and Week 8 of each treatment period
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Week 28
measure: Relative Change From Study Baseline in ppFEV1 at Average of Week 4 and Week 8
timeFrame: Baseline, Week 4 and Week 8 of each treatment period
measure: Absolute Change From Study Baseline in Sweat Chloride at Average of Week 4 and Week 8
timeFrame: Baseline, Week 4 and Week 8 of each treatment period
measure: Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661), IVA and IVA Metabolite (M1 IVA) After Administration of VX-661/IVA Combination Therapy
timeFrame: Pre-morning dose on Week 8 of each treatment period
measure: Ctrough of IVA and IVA Metabolite (M1 IVA) After Administration of IVA Monotherapy
timeFrame: Pre-morning dose on Week 8 of each treatment period
Other outcomes:
Locations:
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state: Virginia
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city: Milwaukee
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state: Wisconsin
city: Adelaide
country: Australia
city: Melbourne
country: Australia
city: South Brisbane
country: Australia
city: Westmead
country: Australia
city: Gent
country: Belgium
city: Montreal
country: Canada
city: Quebec City
country: Canada
city: Toronto
country: Canada
city: Vancouver
country: Canada
city: Marseille cedex 20
country: France
state: Bouches-du-Rhone
city: Montpellier cedex 5
country: France
state: Herault
city: Rennes cedex 09
country: France
state: Ille Et Vilaine
city: Lille cedex
country: France
state: Nord
city: Paris cedex 14
country: France
state: Paris
city: Paris cedex 15
country: France
state: Paris
city: Bron
country: France
state: Rhone
city: Bordeaux Cedex
country: France
city: Muenchen
country: Germany
state: Bayern
city: Munchen
country: Germany
state: Bayern
city: Hannover
country: Germany
state: Niedersachsen
city: Essen
country: Germany
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city: Jena
country: Germany
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city: Jerusalem
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country: Italy
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country: Italy
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country: Italy
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country: Netherlands
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country: Netherlands
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country: Netherlands
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country: Netherlands
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city: St Gallen
country: Switzerland
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country: Switzerland
city: Exeter
country: United Kingdom
state: Devon
city: London
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state: Greater London
city: Manchester
country: United Kingdom
state: Greater Manchester
city: Southampton
country: United Kingdom
state: Hampshire
city: Liverpool
country: United Kingdom
state: Lancashire
city: Glasgow
country: United Kingdom
state: Strathclyde
city: Leeds
country: United Kingdom
state: West Yorkshire
Study officials:
References:
citation: Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
citation: Rowe SM, Daines C, Ringshausen FC, Kerem E, Wilson J, Tullis E, Nair N, Simard C, Han L, Ingenito EP, McKee C, Lekstrom-Himes J, Davies JC. Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis. N Engl J Med. 2017 Nov 23;377(21):2024-2035. doi: 10.1056/NEJMoa1709847. Epub 2017 Nov 3.