Study to Evaluate Safety and Efficacy of VX-661 in Combination With Ivacaftor in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation With an Open-Label Expansion

Cystic Fibrosis Clinical Trial

Official title:

A Phase 2, Randomized, Multicenter, Double Blind, Placebo Controlled Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-661 in Combination With Ivacaftor for 12 Weeks in Subjects With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation With an Open-Label Extension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02070744
• Other study ID #: VX13-661-103
• Status: Completed
• Phase: Phase 2
• First received: February 21, 2014
• Last updated: March 14, 2018
• Start date: March 2014
• Est. completion date: May 27, 2016

Study information

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

Clinical Trial Summary

The objective of this study was to evaluate the safety and efficacy of VX-661in combination with ivacaftor in participants with cystic fibrosis (CF) who are homozygous for F508del cystic fibrosis transmembrane conductance regulator (CFTR) mutation

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 27, 2016
• Est. primary completion date: May 27, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Homozygous for the F508del CFTR mutation

• FEV1 =40% and =90% of predicted normal for age, sex, and height

• 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

• Pregnant and nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1 of the PC Phase and Day -7 or Day 1 of the OLE Phase (whichever was applicable)

• Sexually active participants of reproductive potential who are not willing to follow the contraception requirements

• The participant or a close relative of the participant is the investigator or sub investigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• VX-661
Tablet, oral use
• Ivacaftor
Film coated tablet, oral use
• Placebo matched to VX-661
Tablet, oral use
• Placebo matched to Ivacaftor
Film coated tablet, oral use

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	AE: Any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of PC Phase.	Baseline (PC Phase) up to 112 days
Primary	OLE Phase: Number of Participants With Treatment-Emergent AEs and SAEs	AE: Any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of the OLE Phase.	Baseline (OLE Phase) up to 364 days
Secondary	PC Phase: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of PC Phase.	Baseline (PC Phase), Through Week 12
Secondary	OLE Phase: Absolute Change From Baseline in Percent Predicted FEV1 Through Week 40	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of the OLE Phase.	Baseline (OLE Phase), Through Week 40
Secondary	PC Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 12	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of PC Phase.	Baseline (PC Phase), Through Week 12
Secondary	OLE Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 40	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of the OLE Phase.	Baseline (OLE Phase), Through Week 40
Secondary	PC Phase: Absolute Change From Baseline in Sweat Chloride Through Week 12	Sweat samples were collected using an approved collection device. Baseline was defined as Day 1 of PC Phase.	Baseline (PC Phase), Through Week 12
Secondary	OLE Phase: Absolute Change From Baseline in Sweat Chloride Through Week 40	Sweat samples were collected using an approved collection device. Baseline was defined as Day 1 of the OLE Phase.	Baseline (OLE Phase), Through Week 40
Secondary	PC Phase: Absolute Change From Baseline in Body Weight at Week 12	Baseline was defined as Day 1 of PC Phase.	Baseline (PC Phase), Week 12
Secondary	OLE Phase: Absolute Change From Baseline in Body Weight at Week 40	Baseline was defined as Day 1 of the OLE Phase.	Baseline (OLE Phase), Week 40
Secondary	PC Phase: Absolute Change From Baseline Body Mass Index (BMI) at Week 12	BMI was calculated using following formula: BMI = Weight in kg/height in square meter (m^2). Baseline was defined as Day 1 of PC Phase.	Baseline (PC Phase), Week 12
Secondary	OLE Phase: Absolute Change From Baseline BMI at Week 40	BMI was calculated using following formula: BMI = Weight in kg/height in m^2. Baseline was defined as Day 1 of the OLE Phase.	Baseline (OLE Phase), Week 40
Secondary	PC Phase: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as Day 1 of PC Phase.	Baseline (PC Phase), Through Week 12
Secondary	OLE Phase: Absolute Change From Baseline in CFQ-R Respiratory Domain Score Through Week 40	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as Day 1 of the OLE Phase.	Baseline (OLE Phase), Through Week 40
Secondary	PC Phase: Maximum Plasma Concentration (Cmax) of VX-661 and IVA		Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85
Secondary	PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661	Pharmacokinetic (PK) sampling was performed up to 12 hours post-dose on Day 85. For Arm VX-661 50 mg q12h + IVA 150 mg q12h (VX-661 q12h regimen), area under the concentration versus time curve from time 0 to 12 hours (AUC0-12h) was multiplied by 2 to obtain AUC0-24h.	Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85
Secondary	PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12h) of IVA		Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85
Secondary	PC Phase: Time to Reach Cmax (Tmax) of VX-661 and IVA		Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85