Clinical Trials/NCT02951195

NCT02951195

Completed

Phase 2

A Phase 2, Randomized, Double Blind, Controlled Study to Evaluate the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis

Vertex Pharmaceuticals Incorporated0 sites80 target enrollmentNovember 2016

ConditionsCystic Fibrosis

InterventionsPlacebo VX-152 TEZ/IVA IVA

DrugsVX-152 TEZ/IVA IVA Placebo

Overview

Phase: Phase 2
Intervention: Placebo
Conditions: Cystic Fibrosis
Sponsor: Vertex Pharmaceuticals Incorporated
Enrollment: 80
Primary Endpoint: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

This is a Phase 2, randomized, double blind, placebo and active-controlled, parallel group, multicenter study designed to evaluate the safety and tolerability of VX-152 in Triple Combination (TC) with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF), or who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F508del/F508del).

Registry

clinicaltrials.gov

Start Date

November 2016

End Date

January 2018

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Vertex Pharmaceuticals Incorporated

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Willing and able to comply with scheduled visits, treatment pan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
•Body weight ≥35 kg.
•Sweat chloride value ≥ 60 mmol/L from test results obtained during screening.
•Subjects must have an eligible CFTR genotype:
•Cohorts 1A, 1B, 1C: Heterozygous for F508del and a minimal function mutation known or predicted not to respond to TEZ and/or IVA.
•Cohorts 2A, 2B: Homozygous for F508del.
•Subjects must have an FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height at the Screening Visit.
•Stable CF disease as judged by the investigator.
•Willing to remain on a stable CF medication regimen through the planned end of treatment or if applicable the Safety Follow-up Visit.

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.
•History of cirrhosis with portal hypertension.
•Risk factors for Torsade de Pointes.
•History of hemolysis.
•Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.
•Clinically significant abnormal laboratory values at screening.
•An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before the first dose of study drug.
•Lung infection with organisms associated with a more rapid decline in pulmonary status.
•An acute illness not related to CF within 14 days before the first dose of study drug.
•A standard digital ECG demonstrating QTc \>450 msec at screening.

Arms & Interventions

Part 1: Placebo

Intervention: Placebo

Part 1 Cohort 1A: TC

Intervention: VX-152

Part 1 Cohort 1A: TC

Intervention: TEZ/IVA

Part 1 Cohort 1A: TC

Intervention: IVA

Part 1 Cohort 1B: TC

Intervention: VX-152

Part 1 Cohort 1B: TC

Intervention: TEZ/IVA

Part 1 Cohort 1B: TC

Intervention: IVA

Part 1 Cohort 1C: TC

Intervention: VX-152

Part 1 Cohort 1C: TC

Intervention: TEZ/IVA

Part 1 Cohort 1C: TC

Intervention: IVA

Part 2 Cohort 2A: TEZ/IVA

Intervention: TEZ/IVA

Part 2 Cohort 2A: TEZ/IVA

Intervention: IVA

Part 2 Cohort 2A: TEZ/IVA

Intervention: Placebo

Part 2 Cohort 2A: TC

Intervention: VX-152

Part 2 Cohort 2A: TC

Intervention: TEZ/IVA

Part 2 Cohort 2A: TC

Intervention: IVA

Part 2 Cohort 2B: TEZ/IVA

Intervention: TEZ/IVA

Part 2 Cohort 2B: TEZ/IVA

Intervention: IVA

Part 2 Cohort 2B: TEZ/IVA

Intervention: Placebo

Part 2 Cohort 2B: TC

Intervention: VX-152

Part 2 Cohort 2B: TC

Intervention: TEZ/IVA

Part 2 Cohort 2B: TC

Intervention: IVA

Outcomes

Primary Outcomes

Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Time Frame: Day 1 Through Safety Follow-up Visit (Up to Day 43 for Part 1 and Day 71 for Part 2)

Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A

Time Frame: From Baseline at Day 15

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Absolute Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B

Time Frame: From Baseline Through Day 29

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Secondary Outcomes

Absolute Change in Sweat Chloride Concentrations at Day 15 for Part 1 and Part 2 Cohort 2A(From Baseline at Day 15)
Absolute Change in Sweat Chloride Concentrations Through Day 29 for Part 2 Cohort 2B(From Baseline Through Day 29)
Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A(From Baseline at Day 15)
Relative Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B(From Baseline Through Day 29)
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 15 for Part 1 and Part 2 Cohort 2A(From Baseline at Day 15)
Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 29 for Part 2 Cohort 2B(From Baseline at Day 29)
Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA(Pre-dose at Day 8, Day 15 and Day 29)