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

Phase 2

Completed

• Conditions: Cystic Fibrosis
• Interventions: Drug: Tezacaftor/Ivacaftor matching placebo; Drug: Tezacaftor/Ivacaftor; Drug: Ivacaftor matching placebo; Drug: Ivacaftor

• Registration Number: NCT02508207
• Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-07-23
• Study First Submitted QC: 2015-07-23
• Study First Posted: 2015-07-24
• Study Start: 2016-02
• Primary Completion: 2017-06
• Study Completion: 2017-06
• Status Verified: 2018-06
• Results First Submitted: 2018-06-29
• Results First Submitted QC: 2018-06-29
• Results First Posted: 2018-07-27
• Last Update Submitted: 2021-06-28
• Last Update Posted: 2021-07-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Ivacaftor matching 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.
Placebo	Tezacaftor/Ivacaftor matching 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.
TEZ/IVA	Tezacaftor/Ivacaftor	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.
TEZ/IVA	Ivacaftor	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.

Primary Outcome Measures

Name	Time	Method
Absolute Change From Baseline in Mucociliary Clearance (MCC) at Day 28	Baseline, 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.

Secondary Outcome Measures

Name	Time	Method
Absolute Change From Baseline in Sweat Chloride at Day 29	Baseline, Day 29
Absolute Change From Baseline in Small-bowel Area Under the Curve (AUC) Over 1-minute Mean pH Increments at Day 29	Baseline, Day 29	Absolute change from Baseline in small bowel AUC over 1-minute mean pH increments through 30 minutes at Day 29 was assessed.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline up to Day 57
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 28	Baseline, 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.