A Study Evaluating the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis

Cystic Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02951195
• Other study ID #: VX16-152-102
• Status: Completed
• Phase: Phase 2
• Start date: November 2016
• Est. completion date: January 2018

Study information

• Verified date: January 2021
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: January 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

• History of solid organ or hematological transplantation.

• History or evidence of cataract or lens opacity determined to be clinically significant by the ophthalmologist or optometrist, based on the ophthalmologic examination during the Screening Period.

• History of alcohol or drug abuse in the past year, including but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator.

• Ongoing or prior participation in an investigational drug study with certain exceptions.

• Use of commercially available CFTR modulator within 14 days before screening (applies only to Cohorts 1A, 1B, and 1C).

• Pregnant or nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• VX-152
Tablet for oral administration.
• TEZ/IVA
Fixed-dose combination tablet for oral administration.
• IVA
Tablet for oral administration.
• Placebo
Placebo matched to VX-152.
• Placebo
Placebo matched to VX-152/TEZ/IVA triple combination (TC).

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	Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		Day 1 Through Safety Follow-up Visit (Up to Day 43 for Part 1 and Day 71 for Part 2)
Primary	Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	From Baseline at Day 15
Primary	Absolute Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	From Baseline Through Day 29
Secondary	Absolute Change in Sweat Chloride Concentrations at Day 15 for Part 1 and Part 2 Cohort 2A	Sweat samples were collected using an approved collection device.	From Baseline at Day 15
Secondary	Absolute Change in Sweat Chloride Concentrations Through Day 29 for Part 2 Cohort 2B	Sweat samples were collected using an approved collection device.	From Baseline Through Day 29
Secondary	Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	From Baseline at Day 15
Secondary	Relative Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	From Baseline Through Day 29
Secondary	Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 15 for Part 1 and Part 2 Cohort 2A	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, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.	From Baseline at Day 15
Secondary	Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 29 for Part 2 Cohort 2B	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, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.	From Baseline at Day 29
Secondary	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