NCT03460990

Brief Summary

This study will evaluate the efficacy of VX-659 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation (F/F).

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
116

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started May 2018

Shorter than P25 for phase_3

Geographic Reach
6 countries

46 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 1, 2018

Completed
8 days until next milestone

First Posted

Study publicly available on registry

March 9, 2018

Completed
2 months until next milestone

Study Start

First participant enrolled

May 1, 2018

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 26, 2018

Completed
12 days until next milestone

Study Completion

Last participant's last visit for all outcomes

October 8, 2018

Completed
1 year until next milestone

Results Posted

Study results publicly available

October 17, 2019

Completed
Last Updated

October 17, 2019

Status Verified

September 1, 2019

Enrollment Period

5 months

First QC Date

March 1, 2018

Results QC Date

September 26, 2019

Last Update Submit

September 26, 2019

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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.

    From Baseline at Week 4

Secondary Outcomes (4)

  • Absolute Change in Sweat Chloride (SwCl)

    From Baseline at Week 4

  • Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score

    From Baseline at Week 4

  • Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)

  • Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA

    From Day 1 and Week 4

Study Arms (2)

TEZ/IVA

ACTIVE COMPARATOR

Following a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period.

Drug: TEZ/IVADrug: IVADrug: Placebo

VX-659/TEZ/IVA TC

EXPERIMENTAL

Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.

Drug: VX-659/TEZ/IVADrug: IVADrug: Placebo

Interventions

Participants received VX-659/TEZ/IVA orally once daily in the morning.

Also known as: VX-659/VX-661/VX-770, VX-659/tezacaftor/ivacaftor
VX-659/TEZ/IVA TC

Participants received TEZ/IVA orally once daily in the morning.

Also known as: VX-661/VX-770, tezacaftor/ivacaftor
TEZ/IVA
IVADRUG

Participants received IVA orally once daily in the evening.

Also known as: VX-770, ivacaftor
TEZ/IVAVX-659/TEZ/IVA TC

Participants received placebo matched TEZ/IVA orally once daily in the morning.

VX-659/TEZ/IVA TC

Eligibility Criteria

Age12 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Homozygous for the F508del mutation (F/F)
  • Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height

You may not qualify if:

  • Clinically significant cirrhosis with or without portal hypertension
  • Lung infection with organisms associated with a more rapid decline in pulmonary status
  • Solid organ or hematological transplantation

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (46)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Yale New Haven Medical Center

New Haven, Connecticut, 06511, United States

Location

University of Miami/Miller School of Medicine

Miami, Florida, 33136, United States

Location

St. Luke's CF Center of Idaho

Boise, Idaho, 83712, United States

Location

Advocate Children's Hospital- Park Ridge/ North Suburban Pulmonary and Critical Care Consultants

Niles, Illinois, 60714, United States

Location

Indiana Clinical Research Center, IU Health University Hospital

Indianapolis, Indiana, 46202, United States

Location

The University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

The Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Helen DeVos Children's Hospital CF Center

Grand Rapids, Michigan, 49503, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Washington University School of Medicine / St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Rutgers-Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

Northwell Health, Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Respiratory Diseases of Children and Adolescents

Oklahoma City, Oklahoma, 73211, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15224, United States

Location

Sanford Research/ USD

Sioux Falls, South Dakota, 57105, United States

Location

University of Tennessee Medical Center-Adult Cystic Fibrosis Clinic

Knoxville, Tennessee, 37920, United States

Location

Children's Foundation Research Center/ Le Bonheur Children's Hospital

Memphis, Tennessee, 38103, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah/ Primary Children's Medical Center

Salt Lake City, Utah, 84132, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

The Alfred Hospital

Melbourne, Victoria, Australia

Location

Royal Adelaide Hospital

Adelaide, Australia

Location

Prince Charles Hospital

Chermside, Australia

Location

Institute for Respiratory Health Inc./ Sir Charles Gairdner Hospital

Nedlands, Australia

Location

John Hunter Hospital & Hunter Medical Research Institute

New Lambton Heights, Australia

Location

Charite Paediatric Pulmonology Department

Berlin, Germany

Location

Pneumologische Praxis Pasing

München, Germany

Location

Cork University Hospital

Dublin, Ireland

Location

Our Lady's Children's Hospital

Dublin, Ireland

Location

St. Vincent's University Hospital

Dublin, Ireland

Location

Hospital Universitari Vall d Hebron

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron Servicio de Broncoscopia

Barcelona, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

Papworth Hospital NHS Foundation Trust, Papworth Everard

Cambridge, United Kingdom

Location

Liverpool Heart and Chest Hospital

Liverpool, United Kingdom

Location

Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital

London, United Kingdom

Location

Wythenshawe Hospital

Manchester, United Kingdom

Location

University Hospital Llandough

Penarth, United Kingdom

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

ivacaftortezacaftor, ivacaftor drug combination

Condition Hierarchy (Ancestors)

Pancreatic DiseasesDigestive System DiseasesLung DiseasesRespiratory Tract DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesInfant, Newborn, Diseases

Results Point of Contact

Title
Medical Monitor
Organization
Vertex Pharmaceuticals Incorporated

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 1, 2018

First Posted

March 9, 2018

Study Start

May 1, 2018

Primary Completion

September 26, 2018

Study Completion

October 8, 2018

Last Updated

October 17, 2019

Results First Posted

October 17, 2019

Record last verified: 2019-09

Locations