A Phase 2 Study to Evaluate Effects of VX-661/Ivacaftor on Lung and Extrapulmonary Systems in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation

A Phase 2, Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Exploratory Study to Evaluate Effects of VX-661 in Combination With Ivacaftor on Lung and Extrapulmonary Systems in Subjects Aged 18 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation

To evaluate the clinical mechanisms of action in lung and extrapulmonary systems of VX-661 (tezacaftor; TEZ) in combination with ivacaftor (IVA) (TEZ/IVA) in participants with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Ivacaftor; Drug: Tezacaftor/Ivacaftor matching placebo; Drug: Ivacaftor matching placebo; Drug: Tezacaftor/Ivacaftor

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
  • Indiana
    • Indianapolis, Indiana, United States
  • Maryland
    • Baltimore, Maryland, United States
  • North Carolina
    • Chapel Hill, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
    • Toledo, Ohio, United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female participants, homozygous for the F508del CFTR mutation
• Confirmed diagnosis of CF by sweat chloride testing
• Forced Expiratory Volume in 1 Second (FEV1) ≥40% and ≤90% of predicted normal for age, sex, and height at Screening Visit
• 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 subject.
• An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before Day 1
• History or evidence of clinically significant findings on ophthalmologic examination during the Screening Period.
• History of solid organ or hematological transplantation
• Pregnant or nursing females
• Participants who have had radiation exposure within 1 year before the first mucociliary clearance (MCC) procedure that would cause them to exceed federal regulations by participating in this study
• In the opinion of the investigator, unable to adequately perform inhalation maneuvers during the MCC procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received placebo matched to tezacaftor (TEZ)/ivacaftor (IVA) fixed dose combination (FDC) tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 29 days.	Drug: Tezacaftor/Ivacaftor matching placebo; Drug: Ivacaftor matching placebo
Experimental: TEZ/IVA; Participants received 100 milligram (mg) TEZ/150 mg IVA FDC tablet orally once daily in the morning followed by 150 mg IVA tablet orally once daily in the evening for 29 days.	Drug: Ivacaftor; Drug: Tezacaftor/Ivacaftor; Tezacaftor/Ivacaftor FDC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change From Baseline in Mucociliary Clearance (MCC) at Day 28	MCC was assessed using an imaging technique that enables the tracking of mucus within the airways. MCC was expressed as the percentage of whole-lung clearance through 60 minutes at Baseline and Day 28.	Baseline, Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 28	Percent predicted FEV1 is the ratio of FEV1 to the predicted FEV1, expressed as a percentage. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	Baseline, Day 28
Absolute Change From Baseline in Small-bowel Area Under the Curve (AUC) Over 1-minute Mean pH Increments at Day 29	Absolute change from Baseline in small bowel AUC over 1-minute mean pH increments through 30 minutes at Day 29 was assessed.	Baseline, Day 29
Absolute Change From Baseline in Sweat Chloride at Day 29		Baseline, Day 29
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)		Baseline up to Day 57

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: July 23, 2015
• First Submitted That Met QC Criteria: July 23, 2015
• First Posted (Estimate): July 24, 2015

Study Record Updates

• Last Update Posted (Actual): July 19, 2021
• Last Update Submitted That Met QC Criteria: June 28, 2021
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Ivacaftor
• Other Study ID Numbers: VX14-661-111