search
Back to results

A Study Evaluating the Safety and Efficacy of VX-659 Combination Therapy in Subjects With Cystic Fibrosis

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
VX-659
TEZ/IVA
IVA
Placebo (matched to VX-659/TEZ/IVA)
TEZ
VX-561
Placebo (matched to VX-659/TEZ/VX-561)
Sponsored by
Vertex Pharmaceuticals Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Body weight ≥35 kg.

  • Subjects must have an eligibleCFTR genotype.

    • Part 1 and Part 3: Heterozygous for F508del and an MF mutation (F/MF)
    • Part 2: Homozygous for F508del (F/F)
  • FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height

Key Exclusion Criteria:

  • History of clinically significant cirrhosis with or without portal hypertension.
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Lung infection with organisms associated with a more rapid decline in pulmonary status.
  • History of solid organ or hematological transplantation.

Other protocol defined Inclusion/Exclusion criteria may apply.

Sites / Locations

  • Yale New Haven Hospital
  • University of Miami/Miller School of Medicine
  • Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants
  • Indiana University Health
  • The University of Iowa Hospitals and Clinics
  • The Johns Hopkins Hospital/ Johns Hopkins Hospital, David Rubenstein Child Health Building
  • Boston Children's Hospital
  • University of Massachusetts Memorial Medical Center
  • University of Michigan Health System
  • Helen DeVos Children's Hospital CF Center
  • Children's Mercy Hospital
  • Rutgers-Robert Wood Johnson Medical School/ Rutgers-Robert Wood Johnson Medical School, Clinical Research Center
  • Albany Medical College
  • Northwell Health, Long Island Jewish Medical Center
  • Columbia University Medical Center
  • SUNY Upstate Medical University
  • Respiratory Diseases of Children & Adolescents
  • Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
  • Sanford Research / USD
  • University of Tennessee Medical Center-Adult Cystic Fibrosis Clinic
  • Children's Foundation Research Center / Le Bonheur Children's Hospital
  • Vanderbilt University Medical Center
  • University of Utah / Primary Children's Medical Center
  • Seattle Children's Hospital
  • Providence Pediatric Pulmonary & Allergy/Immunology Clinic
  • Cork University Hospital
  • St. Vincent's University Hosptial
  • Galway University Hospitals
  • University Hospital Limerick
  • Carmel Medical Center
  • Ruth Children's Hospital Rambam Health Care Campus
  • Hadassah Medical Organization
  • The Chaim Sheba medical center
  • Schneider Children's Medical Center
  • Birmingham Heartlands Hospital
  • Papworth Hospital NHS Foundation Trust, Papworth Everard
  • University Hospital Llandough in Cardiff
  • Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
  • The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
  • Greater Glasgow and Clyde NHS Board, Glasgow Clinical Research Facility
  • Southampton University Hospitals NHS Foundation Trust
  • Regional Respiratory Centre Belfast City Hospital
  • Royal Brompton & Harefied NHS Foundation Trust
  • University Hospital of South Manchester NHS Trust, North West Lung Centre
  • Liverpool Heart and Chest Hospital
  • Nottingham University Hospitals NHS Trust
  • Ruth Children's Hospital Rambam Health Care Campus

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Active Comparator

Experimental

Placebo Comparator

Experimental

Arm Label

Part 1: Placebo

Part 1: VX-659/TEZ/IVA TC - Low Dose

Part 1: VX-659/TEZ/IVA TC - Medium Dose

Part 1: VX-659/TEZ/IVA TC - High Dose

Part 2: TEZ/IVA

Part 2: VX-659/TEZ/IVA TC

Part 3: Placebo

Part 3: VX-659/TEZ/VX-561 TC

Arm Description

Participants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched TEZ/IVA in washout period for 4 days.

Participants received VX-659 80 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.

Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.

Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.

Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.

Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.

Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.

Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks.

Outcomes

Primary Outcome Measures

Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Secondary Outcome Measures

Absolute Change in Sweat Chloride Concentrations
Sweat samples were collected using an approved collection device.
Relative Change in ppFEV1
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
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.
Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561

Full Information

First Posted
July 18, 2017
Last Updated
March 29, 2021
Sponsor
Vertex Pharmaceuticals Incorporated
search

1. Study Identification

Unique Protocol Identification Number
NCT03224351
Brief Title
A Study Evaluating the Safety and Efficacy of VX-659 Combination Therapy in Subjects With Cystic Fibrosis
Official Title
A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of VX-659 Combination Therapy in Subjects Aged 18 Years and Older With Cystic Fibrosis
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
August 8, 2017 (Actual)
Primary Completion Date
February 28, 2018 (Actual)
Study Completion Date
February 28, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a Phase 2, randomized, double-blind, placebo- and tezacaftor/ivacaftor (TEZ/IVA)-controlled, parallel-group, 3-part, multicenter study designed to evaluate the safety and efficacy of VX-659 in triple combination (TC) with TEZ and IVA in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F/F genotype), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ, IVA, or TEZ/IVA (F/MF genotypes).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
124 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched TEZ/IVA in washout period for 4 days.
Arm Title
Part 1: VX-659/TEZ/IVA TC - Low Dose
Arm Type
Experimental
Arm Description
Participants received VX-659 80 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.
Arm Title
Part 1: VX-659/TEZ/IVA TC - Medium Dose
Arm Type
Experimental
Arm Description
Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.
Arm Title
Part 1: VX-659/TEZ/IVA TC - High Dose
Arm Type
Experimental
Arm Description
Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.
Arm Title
Part 2: TEZ/IVA
Arm Type
Active Comparator
Arm Description
Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.
Arm Title
Part 2: VX-659/TEZ/IVA TC
Arm Type
Experimental
Arm Description
Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.
Arm Title
Part 3: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.
Arm Title
Part 3: VX-659/TEZ/VX-561 TC
Arm Type
Experimental
Arm Description
Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks.
Intervention Type
Drug
Intervention Name(s)
VX-659
Intervention Description
Tablet for oral administration.
Intervention Type
Drug
Intervention Name(s)
TEZ/IVA
Other Intervention Name(s)
VX-661/VX-770, Tezacaftor/Ivacaftor
Intervention Description
TEZ/IVA fixed-dose combination tablet for oral administration.
Intervention Type
Drug
Intervention Name(s)
IVA
Other Intervention Name(s)
VX-770, Ivacaftor
Intervention Description
Tablet for oral administration.
Intervention Type
Drug
Intervention Name(s)
Placebo (matched to VX-659/TEZ/IVA)
Intervention Description
Placebo matched to VX-659 and TEZ/IVA.
Intervention Type
Drug
Intervention Name(s)
TEZ
Other Intervention Name(s)
VX-661, Tezacaftor
Intervention Description
Tablet for oral administration.
Intervention Type
Drug
Intervention Name(s)
VX-561
Other Intervention Name(s)
CTP-656
Intervention Description
Tablet for oral administration.
Intervention Type
Drug
Intervention Name(s)
Placebo (matched to VX-659/TEZ/VX-561)
Intervention Description
Placebo matched to VX-659, TEZ and VX-561.
Primary Outcome Measure Information:
Title
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 (up to Day 61 for Part 1, Day 85 for Part 2 and Day 57 for Part 3)
Title
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame
From Baseline Through Day 29
Secondary Outcome Measure Information:
Title
Absolute Change in Sweat Chloride Concentrations
Description
Sweat samples were collected using an approved collection device.
Time Frame
From Baseline Through Day 29
Title
Relative Change in ppFEV1
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame
From Baseline Through Day 29
Title
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Description
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.
Time Frame
From Baseline at Day 29
Title
Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561
Time Frame
Pre-dose at Day 15 and Day 29

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Body weight ≥35 kg. Subjects must have an eligibleCFTR genotype. Part 1 and Part 3: Heterozygous for F508del and an MF mutation (F/MF) Part 2: Homozygous for F508del (F/F) FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height Key Exclusion Criteria: History of clinically significant cirrhosis with or without portal hypertension. Glucose-6-phosphate dehydrogenase (G6PD) deficiency Lung infection with organisms associated with a more rapid decline in pulmonary status. History of solid organ or hematological transplantation. Other protocol defined Inclusion/Exclusion criteria may apply.
Facility Information:
Facility Name
Yale New Haven Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
University of Miami/Miller School of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants
City
Morton Grove
State/Province
Illinois
ZIP/Postal Code
60053
Country
United States
Facility Name
Indiana University Health
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
The University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
The Johns Hopkins Hospital/ Johns Hopkins Hospital, David Rubenstein Child Health Building
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02155
Country
United States
Facility Name
University of Massachusetts Memorial Medical Center
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
University of Michigan Health System
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Helen DeVos Children's Hospital CF Center
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Rutgers-Robert Wood Johnson Medical School/ Rutgers-Robert Wood Johnson Medical School, Clinical Research Center
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08902
Country
United States
Facility Name
Albany Medical College
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Northwell Health, Long Island Jewish Medical Center
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11040
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
SUNY Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Respiratory Diseases of Children & Adolescents
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Sanford Research / USD
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57104
Country
United States
Facility Name
University of Tennessee Medical Center-Adult Cystic Fibrosis Clinic
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Facility Name
Children's Foundation Research Center / Le Bonheur Children's Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Utah / Primary Children's Medical Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84014
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Providence Pediatric Pulmonary & Allergy/Immunology Clinic
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
Cork University Hospital
City
Cork
Country
Ireland
Facility Name
St. Vincent's University Hosptial
City
Dublin
Country
Ireland
Facility Name
Galway University Hospitals
City
Galway
Country
Ireland
Facility Name
University Hospital Limerick
City
Limerick
Country
Ireland
Facility Name
Carmel Medical Center
City
Haifa
Country
Israel
Facility Name
Ruth Children's Hospital Rambam Health Care Campus
City
Haifa
Country
Israel
Facility Name
Hadassah Medical Organization
City
Jerusalem
Country
Israel
Facility Name
The Chaim Sheba medical center
City
Ramat Gan
Country
Israel
Facility Name
Schneider Children's Medical Center
City
Tikvah
Country
Israel
Facility Name
Birmingham Heartlands Hospital
City
Birmingham
ZIP/Postal Code
B95SS
Country
United Kingdom
Facility Name
Papworth Hospital NHS Foundation Trust, Papworth Everard
City
Cambridge
Country
United Kingdom
Facility Name
University Hospital Llandough in Cardiff
City
Cardiff
Country
United Kingdom
Facility Name
Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
City
Devon
Country
United Kingdom
Facility Name
The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
City
Fulham
Country
United Kingdom
Facility Name
Greater Glasgow and Clyde NHS Board, Glasgow Clinical Research Facility
City
Glasgow
Country
United Kingdom
Facility Name
Southampton University Hospitals NHS Foundation Trust
City
Hampshire
Country
United Kingdom
Facility Name
Regional Respiratory Centre Belfast City Hospital
City
London
Country
United Kingdom
Facility Name
Royal Brompton & Harefied NHS Foundation Trust
City
London
Country
United Kingdom
Facility Name
University Hospital of South Manchester NHS Trust, North West Lung Centre
City
Manchester
Country
United Kingdom
Facility Name
Liverpool Heart and Chest Hospital
City
Merseyside
Country
United Kingdom
Facility Name
Nottingham University Hospitals NHS Trust
City
Nottingham
Country
United Kingdom
Facility Name
Ruth Children's Hospital Rambam Health Care Campus
City
Nottingham
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
33331662
Citation
Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
Results Reference
derived
PubMed Identifier
30334693
Citation
Davies JC, Moskowitz SM, Brown C, Horsley A, Mall MA, McKone EF, Plant BJ, Prais D, Ramsey BW, Taylor-Cousar JL, Tullis E, Uluer A, McKee CM, Robertson S, Shilling RA, Simard C, Van Goor F, Waltz D, Xuan F, Young T, Rowe SM; VX16-659-101 Study Group. VX-659-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. N Engl J Med. 2018 Oct 25;379(17):1599-1611. doi: 10.1056/NEJMoa1807119. Epub 2018 Oct 18.
Results Reference
derived

Learn more about this trial

A Study Evaluating the Safety and Efficacy of VX-659 Combination Therapy in Subjects With Cystic Fibrosis

We'll reach out to this number within 24 hrs