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

Phase 2CompletedNCT02070744

Vertex Pharmaceuticals Incorporated40 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Cystic Fibrosis

Interventions

VX-661DRUG

Tablet, oral use

IvacaftorDRUG

Film coated tablet, oral use

Placebo matched to VX-661DRUG

Tablet, oral use

Placebo matched to Ivacaftor

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (23)

Unnamed facility

Birmingham, Alabama, United States

Unnamed facility

Palo Alto, California, United States

Outcomes

Primary Outcomes

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.

Time frame: Baseline (PC Phase) up to 112 days

OLE Phase: Number of Participants With Treatment-Emergent AEs and SAEs

Time frame: Baseline (OLE Phase) up to 364 days

Secondary Outcomes

PC Phase: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12

Data from ClinicalTrials.gov

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Film coated tablet, oral use

Unnamed facility

Stanford, California, United States

Unnamed facility

Altamonte Springs, Florida, United States

Unnamed facility

Miami, Florida, United States

Unnamed facility

Orlando, Florida, United States

Unnamed facility

Tampa, Florida, United States

Unnamed facility

Boise, Idaho, United States

Unnamed facility

Chicago, Illinois, United States

Unnamed facility

Boston, Massachusetts, United States

...and 13 more locations

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.

Time frame: Baseline (PC Phase), Through Week 12

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.

Time frame: Baseline (OLE Phase), Through Week 40

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.

Time frame: Baseline (PC Phase), Through Week 12

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.

Time frame: Baseline (OLE Phase), Through Week 40

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.

Time frame: Baseline (PC Phase), Through Week 12

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.

Time frame: Baseline (OLE Phase), Through Week 40

PC Phase: Absolute Change From Baseline in Body Weight at Week 12

Baseline was defined as Day 1 of PC Phase.

Time frame: Baseline (PC Phase), Week 12

OLE Phase: Absolute Change From Baseline in Body Weight at Week 40

Baseline was defined as Day 1 of the OLE Phase.

Time frame: Baseline (OLE Phase), Week 40

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.

Time frame: Baseline (PC Phase), Week 12

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.

Time frame: Baseline (OLE Phase), Week 40

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.

Time frame: Baseline (PC Phase), Through Week 12

OLE Phase: Absolute Change From Baseline in CFQ-R Respiratory Domain Score Through Week 40

Time frame: Baseline (OLE Phase), Through Week 40

PC Phase: Maximum Plasma Concentration (Cmax) of VX-661 and IVA

Time frame: Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85

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.

Time frame: Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85

PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12h) of IVA

Time frame: Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85

PC Phase: Time to Reach Cmax (Tmax) of VX-661 and IVA

Time frame: Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85