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

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ClinicalTrials.gov Identifier: NCT02392234

Recruitment Status : Completed

First Posted : March 18, 2015

Results First Posted : June 12, 2018

Last Update Posted : June 12, 2018

Sponsor:

Information provided by (Responsible Party):

Vertex Pharmaceuticals Incorporated

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: VX-661/Ivacaftor Drug: Ivacaftor Drug: Placebo matched to VX-661/ ivacaftor Drug: Placebo matched to Ivacaftor	Phase 3

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	248 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Treatment
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 Start Date :	March 2015
Actual Primary Completion Date :	February 2017
Actual Study Completion Date :	February 2017

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Ivacaftor

Genetic and Rare Diseases Information Center resources: Cystic Fibrosis

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: VX-661/Ivacaftor combination	Drug: VX-661/Ivacaftor Fixed dose combination tablet, oral use Other Name: VX-661+VX-770 Drug: Ivacaftor Tablet, oral use Other Name: IVA, VX-770 Drug: Placebo matched to Ivacaftor Tablet, oral use
Experimental: Ivacaftor monotherapy	Drug: Ivacaftor Tablet, oral use Other Name: IVA, VX-770 Drug: Placebo matched to VX-661/ ivacaftor Fixed dose combination tablet, oral use
Placebo Comparator: Placebo	Drug: Placebo matched to VX-661/ ivacaftor Fixed dose combination tablet, oral use Drug: Placebo matched to Ivacaftor Tablet, oral use

Outcome Measures

Primary Outcome Measures :

Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Week 4 and Week 8 [ Time Frame: Baseline, Week 4 and Week 8 of each treatment period ]
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Secondary Outcome Measures :

Absolute Change From Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Week 4 and Week 8 [ Time Frame: Baseline, Week 4 and Week 8 of each treatment period ]
The CFQ-R assessed respiratory symptoms on a scale with scores ranging from 0 to 100; where higher scores indicated fewer symptoms and better health-related quality of life.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to Week 28 ]
Relative Change From Study Baseline in ppFEV1 at Average of Week 4 and Week 8 [ Time Frame: Baseline, Week 4 and Week 8 of each treatment period ]
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change From Study Baseline in Sweat Chloride at Average of Week 4 and Week 8 [ Time Frame: Baseline, Week 4 and Week 8 of each treatment period ]
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 [ Time Frame: Pre-morning dose on Week 8 of each treatment period ]
Ctrough of IVA and IVA Metabolite (M1 IVA) After Administration of IVA Monotherapy [ Time Frame: Pre-morning dose on Week 8 of each treatment period ]

Eligibility Criteria

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Ages Eligible for Study:	12 Years and older (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02392234

Show 94 Study Locations

Sponsors and Collaborators

Vertex Pharmaceuticals Incorporated

Study Documents (Full-Text)

Documents provided by Vertex Pharmaceuticals Incorporated:

Study Protocol [PDF] June 10, 2016

Statistical Analysis Plan [PDF] February 24, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.


Responsible Party:	Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:	NCT02392234 History of Changes
Other Study ID Numbers:	VX14-661-108 2014-004788-18 ( EudraCT Number )
First Posted:	March 18, 2015 Key Record Dates
Results First Posted:	June 12, 2018
Last Update Posted:	June 12, 2018
Last Verified:	May 2018

Additional relevant MeSH terms:


Fibrosis Cystic Fibrosis Pathologic Processes Pancreatic Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases	Genetic Diseases, Inborn Infant, Newborn, Diseases Ivacaftor Chloride Channel Agonists Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action

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