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A Study of VX-445 Combination Therapy in CF Subjects Homozygous for F508del (F/F)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03525548
Recruitment Status : Completed
First Posted : May 15, 2018
Results First Posted : January 27, 2020
Last Update Posted : January 27, 2020
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Brief Summary:
This study will evaluate the efficacy of VX-445 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)

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: VX-445/TEZ/IVA Drug: TEZ/IVA Drug: IVA Drug: Placebo Phase 3

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 113 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del Mutation (F/F)
Actual Study Start Date : August 3, 2018
Actual Primary Completion Date : December 28, 2018
Actual Study Completion Date : December 28, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis
Drug Information available for: Ivacaftor

Arm Intervention/treatment
Active Comparator: TEZ/IVA
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/IVA
Participants received TEZ/IVA orally once daily in the morning.
Other Names:
  • VX-661/VX-770
  • tezacaftor/ivacaftor

Drug: IVA
Participants received IVA orally once daily in the evening.
Other Names:
  • VX-770
  • ivacaftor

Drug: Placebo
Participants received placebo matched to VX-445/TEZ/IVA orally once daily in the morning.

Experimental: VX-445/TEZ/IVA TC
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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-445/TEZ/IVA
Participants received VX-445/TEZ/IVA orally once daily in the morning.
Other Names:
  • VX-445/VX-661/VX-770
  • VX-445/tezacaftor/ivacaftor

Drug: IVA
Participants received IVA orally once daily in the evening.
Other Names:
  • VX-770
  • ivacaftor

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




Primary Outcome Measures :
  1. Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [ Time Frame: From Baseline at Week 4 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.


Secondary Outcome Measures :
  1. Absolute Change in Sweat Chloride (SwCl) [ Time Frame: From Baseline at Week 4 ]
    Sweat samples were collected using an approved collection device.

  2. Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score [ Time Frame: From Baseline at Week 4 ]
    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 indicate fewer symptoms and better health-related quality of life.

  3. Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 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) ]
  4. Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA [ Time Frame: Day 1 and Week 4 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • 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

Key Exclusion Criteria:

  • 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

Other protocol defined Inclusion/Exclusion criteria may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03525548


Locations
Hide Hide 44 study locations
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United States, Arizona
Banner University of Arizona Medical Center
Tucson, Arizona, United States, 85724
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Miller Children's Hospital/ Long Beach Memorial
Long Beach, California, United States, 90806
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Valley Children's Hospital
Madera, California, United States, 93636
United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206
United States, Florida
Joe DiMaggio Cystic Fibrosis & Pulmonary Center/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital
Hollywood, Florida, United States, 33021
Central Florida Pulmonary Group, PA
Orlando, Florida, United States, 32803
Nemours Children's Hospital
Orlando, Florida, United States, 32827
Tampa General Hospital Cardiac and Lung Transplant Clinic
Tampa, Florida, United States, 33606
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
Saint Francis Medical Center/ Children's Hospital of Illinoise/OSF
Peoria, Illinois, United States, 61637
United States, Louisiana
Tulane Medical Center
New Orleans, Louisiana, United States, 70112
United States, Massachusetts
Massachusetts General Hospital Cystic Fibrosis Center Clinical Research Center
Boston, Massachusetts, United States, 02114
United States, Michigan
Harper University Hospital
Detroit, Michigan, United States, 48201
United States, New York
New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
UNC Marisco Clinical Research Center
Chapel Hill, North Carolina, United States, 27517
United States, Ohio
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States, 44106
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
Dayton Children's Hospital
Dayton, Ohio, United States, 45404
ProMedica Toledo Hospital/ Toledo Children's Hospital/ Pediatric Pulmonary & Cystic Fibrosis Center
Toledo, Ohio, United States, 43606
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
The University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Vermont
Vermont Lung Center
Colchester, Vermont, United States, 05446
United States, Virginia
University of Virginia Primary Care Center
Charlottesville, Virginia, United States, 22908
United States, West Virginia
West Virginia University
Morgantown, West Virginia, United States, 26506
Belgium
Cliniques Universitaires de Bruxelles Hopital Erasme
Brussels, Belgium
Universitair Ziekenhuis Brussel - Campus Jette
Brussels, Belgium
UZ Antwerpen
Edegem, Belgium
Universitair Ziekenhuis Gent
Gent, Belgium
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
Leuven, Belgium
Netherlands
Academic Medical Center
Amsterdam, Netherlands
HagaZiekenhuis van den Haag
Den Haag, Netherlands
University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
Heidelberglaan, Netherlands
UMC St. Radboud
Nijmegen, Netherlands
Erasmus Medical Center
Rotterdam, Netherlands
United Kingdom
The Royal Belfast Hospital for Sick Children
Belfast, United Kingdom
Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
Birmingham, United Kingdom
Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
Exeter, United Kingdom
Leeds General Infirmary
Leeds, United Kingdom
King's College Hospital
London, United Kingdom
Southampton General Hospital
Southampton, United Kingdom
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  Study Documents (Full-Text)

Documents provided by Vertex Pharmaceuticals Incorporated:
Study Protocol  [PDF] July 19, 2018
Statistical Analysis Plan  [PDF] September 25, 2018


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT03525548    
Other Study ID Numbers: VX17-445-103
2018-000184-89 ( EudraCT Number )
First Posted: May 15, 2018    Key Record Dates
Results First Posted: January 27, 2020
Last Update Posted: January 27, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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VX-445
Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Ivacaftor
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action