Study of VX-809 Alone and in Combination With VX-770 in Cystic Fibrosis (CF) Patients Homozygous or Heterozygous for the F508del-CFTR Mutation

September 2, 2015 updated by: Vertex Pharmaceuticals Incorporated

A Phase 2, Multicenter, Double-Blinded, Placebo-Controlled, Multiple-Dose Study to Evaluate Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Lumacaftor Monotherapy, and Lumacaftor and Ivacaftor Combination Therapy in Subjects With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation

The purpose of this study is to evaluate of the safety, efficacy, pharmacokinetics (PK) and pharmacodynamic (PD) effects of lumacaftor (VX-809) alone and when coadministered with ivacaftor (VX-770) in participants with cystic fibrosis, homozygous or heterozygous for the F508del-CFTR mutation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
312

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

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
      • Adelaide, Australia
      • Brisbane, Australia
      • Chermside, Australia
      • Nedlands, Australia
      • Parkville Victoria, Australia
      • Westmead, Australia
  • Belgium
      • Leuven, Belgium
  • France
      • Paris, France
    • Rhone
      • Pierre Benite Cedex, Rhone, France
  • Germany
      • Berlin, Germany
      • Bochum, Germany
      • Essen, Germany
      • Koeln, Germany
    • Thueringen
      • Jena, Thueringen, Germany
  • New Zealand
      • Auckland, New Zealand
      • Christchurch, New Zealand
  • United Kingdom
      • London, United Kingdom
  • United States
    • Alabama
      • Birmingham, Alabama, United States
    • Alaska
      • Anchorage, Alaska, United States
    • California
      • La Jolla, California, United States
      • Long Beach, California, United States
      • Palo Alto, California, United States
      • Sacramento, California, United States
    • Colorado
      • Denver, Colorado, United States
    • Connecticut
      • New Haven, Connecticut, United States
    • Florida
      • Miami, Florida, United States
      • Orlando, Florida, United States
      • Tampa, Florida, United States
    • Georgia
      • Atlanta, Georgia, United States
    • Idaho
      • Boise, Idaho, United States
    • Illinois
      • Chicago, Illinois, United States
    • Iowa
      • Iowa City, Iowa, United States
    • Kansas
      • Kansas City, Kansas, United States
    • Kentucky
      • Lexington, Kentucky, United States
    • Louisiana
      • New Orleans, Louisiana, United States
    • Maryland
      • Baltimore, Maryland, United States
    • Massachusetts
      • Boston, Massachusetts, United States
    • Minnesota
      • Minneapolis, Minnesota, United States
    • Missouri
      • St. Louis, Missouri, United States
    • Nebraska
      • Omaha, Nebraska, United States
    • New Hampshire
      • Lebanon, New Hampshire, United States
    • New York
      • Buffalo, New York, United States
      • New Hyde Park, New York, United States
      • New York, New York, United States
      • Rochester, New York, United States
      • Syracuse, New York, United States
    • North Carolina
      • Chapel Hill, North Carolina, United States
    • Ohio
      • Akron, Ohio, United States
      • Cleveland, Ohio, United States
      • Columbus, Ohio, United States
    • Oklahoma
      • Oklahoma City, Oklahoma, United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
      • Pittsburg, Pennsylvania, United States
      • Pittsburgh, Pennsylvania, United States
    • South Carolina
      • Charleston, South Carolina, United States
    • South Dakota
      • Sioux Falls, South Dakota, 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female participants with confirmed diagnosis of CF
  • Must have the F508del-CFTR mutation on at least 1 allele.
  • FEV1 greater than equal (>=) 40% of predicted normal for age, gender, and height (Knudson standards)(Cohort 1, 2, and 3); FEV1 40-90% of predicted normal for age, gender, and height (Hankinson standards (Cohort 4)
  • Participant of child-bearing potential and who are sexually active must meet the contraception requirements

Exclusion Criteria:

  • History of any illness or condition 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 participant (e.g., cirrhosis with portal hypertension).
  • An acute illness including acute upper or lower respiratory infection, pulmonary exacerbation or changes in therapy (including antibiotics) for pulmonary disease within 14 days (Cohort 1, 2, and 3) or 28 days (Cohort 4) before receiving the first dose of study drug.
  • History of solid organ or hematological transplantation.
  • History of alcohol abuse or drug addiction in the past year, including cannabis, cocaine, and opiates.
  • Ongoing participation in another therapeutic clinical study, or prior participation in an investigational drug study without appropriate washout
  • Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of non-hormonal contraception
  • Participants enrolled in Cohort 1 or Cohort 2 will not be eligible for Cohort 3
  • Ongoing or prior participation in an investigational drug study within 30 days of the Screening Visit
  • Heterozygous participants who participated in Cohort 2 and meet the eligibility criteria for Cohort 4 may participate in Cohort 4
  • Evidence of lens opacity or cataract as determined by the ophthalmologic examination (Cohort 4 only)

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: Factorial Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Cohort 1: Placebo
Participants homozygous (HO) for the F508del-CF transmembrane conductance regulator gene (CFTR) mutation received lumacaftor matched placebo once daily (qd) (Day 1 through Day 14), followed by lumacaftor matched placebo qd in combination with ivacaftor matched placebo every 12 hours (q12h) (Day 15 through Day 21).
Drug: Lumacaftor Placebo
Matching placebo tablet.
Drug: Ivacaftor Placebo
Matching placebo tablet.
Experimental: Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 150 mg q12h
Participants homozygous for the F508del-CFTR mutation received 200 milligram (mg) of lumacaftor (LUM) qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 150 mg of ivacaftor (IVA) q12h (Day 15 through Day 21).
Drug: Lumacaftor
Tablet
Other Names:
  • VX-809, LUM
Drug: Ivacaftor
Tablet.
Other Names:
  • VX-770, IVA
Experimental: Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h
Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 15 through Day 21).
Drug: Lumacaftor
Tablet
Other Names:
  • VX-809, LUM
Drug: Ivacaftor
Tablet.
Other Names:
  • VX-770, IVA
Placebo Comparator: Cohort 2 and 3: Placebo (HO and HE)
Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 28), followed by lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56).
Drug: Lumacaftor Placebo
Matching placebo tablet.
Drug: Ivacaftor Placebo
Matching placebo tablet.
Experimental: Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO)
Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
Drug: Lumacaftor
Tablet
Other Names:
  • VX-809, LUM
Drug: Ivacaftor
Tablet.
Other Names:
  • VX-770, IVA
Experimental: Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO)
Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
Drug: Lumacaftor
Tablet
Other Names:
  • VX-809, LUM
Drug: Ivacaftor
Tablet.
Other Names:
  • VX-770, IVA
Experimental: Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO&HE)
Participants homozygous or heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
Drug: Lumacaftor
Tablet
Other Names:
  • VX-809, LUM
Drug: Ivacaftor
Tablet.
Other Names:
  • VX-770, IVA
Experimental: Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO)
Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone q12h (Day 1 through Day 28), followed by 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
Drug: Lumacaftor
Tablet
Other Names:
  • VX-809, LUM
Drug: Ivacaftor
Tablet.
Other Names:
  • VX-770, IVA
Placebo Comparator: Cohort 4: Placebo
Participants heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 1 through Day 56).
Drug: Lumacaftor Placebo
Matching placebo tablet.
Drug: Ivacaftor Placebo
Matching placebo tablet.
Experimental: Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h
Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56).
Drug: Lumacaftor
Tablet
Other Names:
  • VX-809, LUM
Drug: Ivacaftor
Tablet.
Other Names:
  • VX-770, IVA

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cohort 1: Safety and Tolerability Based on Adverse Events (AEs)
Time Frame: Cohort 1: Day 1 up to 28 days after last dose (Last dose = Day 21)
AE: any untoward medical occurrence in a participant during study; irrespective of relationship with treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent. AE includes serious AEs (SAEs) as well as Non-SAEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to 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. Number of participants with AEs and SAEs are reported. AE that started at/after initial dosing of study drug, or increased in severity after initial dosing of study drug is considered treatment-emergent. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 14) and combination therapy period (Period 2: Day 15 to Day 21).
Cohort 1: Day 1 up to 28 days after last dose (Last dose = Day 21)
Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs)
Time Frame: Cohort 2 and 3: Day 1 up to 28 days after last dose (Last dose = Day 56)
Detailed description is provided in Outcome Measure 1. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 28) and combination therapy period (Period 2: Day 29 to Day 56).
Cohort 2 and 3: Day 1 up to 28 days after last dose (Last dose = Day 56)
Cohort 4: Safety and Tolerability Assessed by Number of Participants With AEs and SAEs
Time Frame: Cohort 4: Day 1 up to 28 days after last dose (Last dose = Day 56)
AEs and SAEs are defined in Outcome Measure 1.
Cohort 4: Day 1 up to 28 days after last dose (Last dose = Day 56)
Cohort 1: Absolute Change From Day 14 in Sweat Chloride at Day 21
Time Frame: Cohort 1: Day 14, Day 21
Cohort 1: Day 14, Day 21
Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56
Time Frame: Cohort 2 and 3: Day 28, Day 56
Cohort 2 and 3: Day 28, Day 56
Cohort 4: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 56
Time Frame: Cohort 4: Baseline, Day 56
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) was calculated using the Hankinson method.
Cohort 4: Baseline, Day 56

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Cohort 1: Absolute Change From Baseline in Sweat Chloride at Day 14
Time Frame: Cohort 1: Baseline, Day 14
Cohort 1: Baseline, Day 14
Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14
Time Frame: Cohort 2: Baseline, Day 14
Cohort 2: Baseline, Day 14
Cohort 4: Absolute Change From Baseline in Sweat Chloride at Day 56
Time Frame: Cohort 4: Baseline, Day 56
Cohort 4: Baseline, Day 56
Cohort 1: Absolute Change From Day 14 in FEV1 at Day 21
Time Frame: Cohort 1: Day 14, Day 21
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Cohort 1: Day 14, Day 21
Cohort 1: Absolute Change From Day 14 in ppFEV1 at Day 21
Time Frame: Cohort 1: Day 14, Day 21
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Cohort 1: Day 14, Day 21
Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56
Time Frame: Cohort 2 and 3: Day 28, Day 56
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Cohort 2 and 3: Day 28, Day 56
Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56
Time Frame: Cohort 2 and 3: Day 28, Day 56
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Cohort 2 and 3: Day 28, Day 56
Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56
Time Frame: Cohort 2 and 3: Baseline, Day 28 and 56
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Cohort 2 and 3: Baseline, Day 28 and 56
Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56
Time Frame: Cohort 2 and 3: Baseline, Day 28 and 56
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Cohort 2 and 3: Baseline, Day 28 and 56
Cohort 4: Relative Change From Baseline in Percent Predicted FEV1 at Day 56
Time Frame: Cohort 4: Baseline, Day 56
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Cohort 4: Baseline, Day 56
Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56
Time Frame: Cohort 2 and 3: Day 28, Day 56
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Cohort 2 and 3: Day 28, Day 56
Cohort 4: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 56
Time Frame: Cohort 4: Baseline, Day 56
CFQ-R respiratory domain is defined in Outcome Measure 17.
Cohort 4: Baseline, Day 56
Cohort 4: Absolute Change From Baseline in Body Mass Index (BMI) at Day 56
Time Frame: Cohort 4: Baseline, Day 56
BMI was defined as weight in kilogram (kg) divided by height*height in square meter (m^2).
Cohort 4: Baseline, Day 56
Cohort 4: Absolute Change From Baseline in Weight at Day 56
Time Frame: Cohort 4: Baseline, Day 56
Cohort 4: Baseline, Day 56

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 15, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 19, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 20, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 5, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VX09-809-102
  • 2010-020413-90 (EudraCT Number)

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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