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

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02392234
• Other study ID #: VX14-661-108
• Secondary ID: 2014-004788-18
• Status: Completed
• Phase: Phase 3
• Start date: March 2015
• Est. completion date: February 2017

Study information

• Verified date: May 2018
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 248
• Est. completion date: February 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• VX-661/Ivacaftor
Fixed dose combination tablet, oral use
• Ivacaftor
Tablet, oral use
• Placebo matched to VX-661/ ivacaftor
Fixed dose combination tablet, oral use
• Placebo matched to Ivacaftor
Tablet, oral use

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Israel,  Italy,  Netherlands,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Week 4 and Week 8	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	Baseline, Week 4 and Week 8 of each treatment period
Secondary	Absolute Change From Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Week 4 and Week 8	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.	Baseline, Week 4 and Week 8 of each treatment period
Secondary	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)		Day 1 up to Week 28
Secondary	Relative Change From Study Baseline in ppFEV1 at Average of Week 4 and Week 8	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	Baseline, Week 4 and Week 8 of each treatment period
Secondary	Absolute Change From Study Baseline in Sweat Chloride at Average of Week 4 and Week 8		Baseline, Week 4 and Week 8 of each treatment period
Secondary	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		Pre-morning dose on Week 8 of each treatment period
Secondary	Ctrough of IVA and IVA Metabolite (M1 IVA) After Administration of IVA Monotherapy		Pre-morning dose on Week 8 of each treatment period