A Study of Lumacaftor in Combination With Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Who Are Homozygous for the F508del-CFTR Mutation (TRANSPORT)

August 15, 2016 updated by: Vertex Pharmaceuticals Incorporated

A Phase 3, Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Lumacaftor in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation

The primary objective of the study was to evaluate the efficacy of lumacaftor in combination with ivacaftor at Week 24 in participants aged 12 years and older with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This was a Phase 3, randomized, double-blind, placebo-controlled, parallel-group multicenter study of orally administered lumacaftor in combination with ivacaftor in participants aged 12 years and older with CF who are homozygous for the F508del-CFTR mutation.

The study included a Screening Period (Day -28 through Day -1), a Treatment Period (Day 1 [first dose of study drug] to Week 24 ± 5 days), and a Safety Follow-up Visit (4 weeks ± 7 days after the Week 24 Visit).

Study Type

Interventional

Enrollment (Actual)

563

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Queensland
      • Brisbane, Queensland, Australia
      • Chermside, Queensland, Australia
      • Herston, Queensland, Australia
      • South Brisbane, Queensland, Australia
    • Western Australia
      • Nedlands, Western Australia, Australia
      • Subiaco, Western Australia, Australia
  • Austria
      • Innsbruck, Austria
      • Wels, Austria
  • Belgium
      • Bruxelles, Belgium
      • Gent, Belgium
      • Leuven, Belgium
      • Liège, Belgium
  • Canada
    • Alberta
      • Calgary, Alberta, Canada
      • Edmonton, Alberta, Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
    • Quebec
      • Montreal, Quebec, Canada
  • Denmark
      • København Ø, Denmark
  • France
      • Bordeaux Cedex, France
      • Paris, France
    • Bouches-du-Rhône
      • Marseille, Bouches-du-Rhône, France
    • Haute Garonne
      • Toulouse cedex 9, Haute Garonne, France
    • Herault
      • Montpellier cedex 5, Herault, France
    • Nord
      • Lille, Nord, France
  • Germany
    • Bayern
      • Muenchen, Bayern, Germany
    • Hessen
      • Frankfurt, Hessen, Germany
      • Giessen, Hessen, Germany
    • Niederachsen
      • Hannover, Niederachsen, Germany
    • Nordrhein Westfalen
      • Bochum, Nordrhein Westfalen, Germany
    • Thueringen
      • Jena, Thueringen, Germany
  • Spain
      • Barcelona, Spain
      • Valencia, Spain
  • United Kingdom
    • Avon
      • Bristol, Avon, United Kingdom
    • Greater London
      • London, Greater London, United Kingdom
    • Merseyside
      • Liverpool, Merseyside, United Kingdom
    • Tyne & Wear
      • Newcastle upon Tyne, Tyne & Wear, United Kingdom
    • West Yorkshire
      • Leeds, West Yorkshire, United Kingdom
  • United States
    • California
      • Oakland, California, United States
      • Sacramento, California, United States
    • Colorado
      • Aurora, Colorado, United States
    • Connecticut
      • Hartford, Connecticut, United States
      • New Haven, Connecticut, United States
    • Florida
      • Jacksonville, Florida, United States
      • Miami, Florida, United States
    • Indiana
      • Indianapolis, Indiana, United States
    • Iowa
      • Iowa City, Iowa, United States
    • Kansas
      • Kansas City, Kansas, United States
    • Kentucky
      • Lexington, Kentucky, United States
    • Maine
      • Portland, Maine, United States
    • Massachusetts
      • Worcester, Massachusetts, United States
    • Michigan
      • Detroit, Michigan, United States
      • Grand Rapids, Michigan, United States
    • Minnesota
      • Minneapolis, Minnesota, United States
    • Mississippi
      • Jackson, Mississippi, United States
    • Missouri
      • St. Louis, Missouri, United States
    • Nebraska
      • Omaha, Nebraska, United States
    • New Jersey
      • Morristown, New Jersey, United States
      • New Brunswick, New Jersey, United States
    • New Mexico
      • Alburquerque, New Mexico, United States
    • New York
      • Albany, New York, United States
      • Buffalo, New York, United States
      • New York, New York, United States
      • Rochester, New York, United States
      • Syracuse, New York, United States
    • Ohio
      • Cleveland, Ohio, United States
      • Columbus, Ohio, United States
      • Toledo, Ohio, United States
    • Oklahoma
      • Oklahoma City, Oklahoma, United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
      • Pittsburgh, Pennsylvania, United States
    • South Carolina
      • Charleston, South Carolina, United States
    • South Dakota
      • Sioux Falls, South Dakota, United States
    • Tennessee
      • Memphis, Tennessee, United States
      • Nashville, Tennessee, United States
    • Texas
      • Dallas, Texas, United States
      • Fort Worth, Texas, United States
      • Houston, Texas, United States
      • San Antonio, Texas, United States
    • Utah
      • Salt Lake City, Utah, United States
    • Virginia
      • Richmond, Virginia, United States
    • Washington
      • Seattle, Washington, United States
      • Spokane, Washington, United States
    • Wisconsin
      • Milwaukee, Wisconsin, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Confirmed diagnosis of CF
  • Homozygous for the F508del CFTR mutation
  • Forced expiratory volume in 1 second (FEV1) greater than or equal to (>=) 40 percent (%) and less than or equal to (=<) 90% of predicted normal for age, sex, and height
  • Willing to remain on a stable CF medication regimen through Week 24 or, if applicable, the Safety Follow up Visit

Exclusion Criteria:

  • An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before first dose of study drug
  • History of solid organ or hematological transplantation
  • History of alcohol or drug abuse in the past year
  • Ongoing or prior participation in an investigational drug study (including studies investigating lumacaftor and/or ivacaftor) within 30 days of screening.
  • Use of strong inhibitors, moderate inducers, or strong inducers of Cytochrome P450 3A (CYP3A) within 14 days before Day 1 of dosing

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo matched to lumacaftor (LUM, VX-809) and ivacaftor (IVA, VX-770) tablet every 12 hours (q12h), up to Week 24.
Drug: Placebo
Matching placebo tablet
Experimental: LUM 600 mg qd/IVA 250 mg q12h
LUM 600 milligram (mg) plus IVA 250 mg fixed-dose combination (FDC) tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
Drug: Lumacaftor Plus Ivacaftor Combination
Fixed dose combination tablet
Other Names:
  • VX-809+VX-770, LUM+IVA
Drug: Ivacaftor
Film-coated tablet
Other Names:
  • VX-770, IVA
Experimental: LUM 400 mg q12h/ IVA 250 mg q12h
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
Drug: Lumacaftor Plus Ivacaftor Combination
Fixed dose combination tablet
Other Names:
  • VX-809+VX-770, LUM+IVA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 24
Time Frame: Baseline, Week 16 and 24
Absolute change from baseline at week 24 was assessed as the average treatment effect at Week 16 and at Week 24. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, race, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years.
Baseline, Week 16 and 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relative Change From Baseline in Percent Predicted FEV1 at Week 24
Time Frame: Baseline, Week 16 and 24
Assessed as the average treatment effect at Week 16 and at Week 24. FEV1 and percent predicted FEV1 are defined in Outcome Measure (OM) 1.
Baseline, Week 16 and 24
Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
Time Frame: Baseline, Week 24
BMI was defined as weight in kilogram (kg) divided by height*height in square meter (m^2).
Baseline, Week 24
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24
Time Frame: Baseline, Week 24
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 (for example, coughing, congestion, wheezing), the scaled score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Baseline, Week 24
Percentage of Participants With Response Based on Percent Predicted FEV1
Time Frame: Week 16 and 24
A participant was considered as a responder if the participant had >=5% increase from baseline in average percent predicted FEV1 at Week 16 and at Week 24 (relative change). FEV1 and percent predicted FEV1 are defined in OM 1. A participant with a missing average relative change from baseline in percent predicted FEV1 at Week 16 and at Week 24 was considered as a non-responder.
Week 16 and 24
Number of Pulmonary Exacerbation Events
Time Frame: through Week 24
The total number of days on study is equal to the Week 24 date or the last dose date (whichever occurred last) minus the first dose date plus 1. The total number of years (48 weeks) on study is equal to the number of days on study divided by 336. Pulmonary exacerbation events per year (48 weeks) are reported.
through Week 24
Absolute Change From Baseline in Weight at Week 24
Time Frame: Baseline, Week 24
Baseline, Week 24
Absolute Change From Baseline in BMI-for-age Z-score at Week 24
Time Frame: Baseline, Week 24
Z-Score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard and how unusual the measurement is with range from -infinity to +infinity; 0: same mean, >0: a greater mean, and <0: a lesser mean than the standard. BMI-for-age z-score was calculated by using centers for disease control and prevention (CDC) growth charts for the pediatric population.
Baseline, Week 24
Time-to-First Pulmonary Exacerbation
Time Frame: through Week 24
Time to first pulmonary exacerbation was assessed using Cox Regression method. For participants who completed 24 weeks of treatment, participants without a pulmonary exacerbation before treatment completion were considered censored at the time of treatment completion or at the Week 24 Visit (whichever occurred last). For participants who prematurely discontinued study treatment, participants without a pulmonary exacerbation through the Week 24 Visit were considered censored at the time of the Week 24 Visit.
through Week 24
Percentage of Participants With At Least 1 Pulmonary Exacerbation Event
Time Frame: through Week 24
through Week 24
Absolute Change From Baseline in Euro Quality of Life Scale (EuroQol) 5-Dimension-3 Level (EQ-5D-3L) Index Score at Week 24
Time Frame: Baseline, Week 24
EQ-5D-3L: participant rated questionnaire to assess health-related quality of life. It consists of EQ-5D descriptive system and EQ-5D Visual Analog Scale (VAS). EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems (1), some problems (2), and extreme problems (3). The 5 dimensional 3-level systems are converted into a single index utility score. Values for theoretically possible health states are calculated using a regression model and weighted according to the social preferences of the Unites States (US) general population. For this population, the possible EQ-5D-3L index scores ranges from -0.11 (that is, 3 for all 5 dimensions) to 1.0 (that is, 1 for all 5 dimensions), where higher scores indicate a better health state.
Baseline, Week 24
Absolute Change From Baseline in EQ-5D-3L VAS Score at Week 24
Time Frame: Baseline, Week 24
The EQ-5D-3L VAS records the participant's self-rated health on a vertical, visual analogue scale where the best state a participant can imagine is marked 100 and the worst state a participant can imagine is marked 0, higher scores indicates a better health state.
Baseline, Week 24
Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domain Scores at Week 24
Time Frame: Baseline, Week 24
The TSQM is a 14-item self-administered questionnaire which measures participants' experiences with their medication on four dimensions: effectiveness, side effects, convenience and global satisfaction. For each dimension, responses are added and transformed to a scale from 0 to 100, where higher scores indicate greater satisfaction.
Baseline, Week 24
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs)
Time Frame: up to Week 28
AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Any AE that increased in severity or that was newly developed at or after the initial dosing of study drug to 28 days after the last dose of study drug is considered treatment-emergent.
up to Week 28
Pre-dose Concentration (Ctrough), Average Pre-dose Concentration (Ctrough,Avg), 3 to 6 Hours Post-dose Concentration (C3-6h), and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Avg)
Time Frame: For C3-6h: 3 to 6 hours after morning dose on Day 1 and 15, Week 4 and 8; For C3-6h,avg 3 to 6 hours after morning dose on Day 15, Week 4 and 8; For Ctrough and Ctrough,avg: before morning dose on Week 4, 8, and 16
Ctrough, Ctrough,avg, C3-6h, and C3-6h,avg for lumacaftor, M28 lumacaftor (lumacaftor metabolite), ivacaftor, M1 ivacaftor (ivacaftor metabolite), and M6 ivacaftor (ivacaftor metabolite) were calculated. C3-6h,avg is average of individual 3 to 6 hours post-dose observed concentrations across Day 15, and Weeks 4 and 8 and Ctrough,avg is average of individual pre-dose observed concentrations across Weeks 4, 8, and 16. This outcome was not planned to be assessed in Placebo arm.
For C3-6h: 3 to 6 hours after morning dose on Day 1 and 15, Week 4 and 8; For C3-6h,avg 3 to 6 hours after morning dose on Day 15, Week 4 and 8; For Ctrough and Ctrough,avg: before morning dose on Week 4, 8, and 16

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vertex Pharmaceuticals Incorporated

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2013

Primary Completion (Actual)

April 1, 2014

Study Completion (Actual)

April 1, 2014

Study Registration Dates

First Submitted

March 4, 2013

First Submitted That Met QC Criteria

March 6, 2013

First Posted (Estimate)

March 8, 2013

Study Record Updates

Last Update Posted (Estimate)

September 27, 2016

Last Update Submitted That Met QC Criteria

August 15, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VX12-809-104

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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