- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02516410
A Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation
May 8, 2018 updated by: Vertex Pharmaceuticals Incorporated
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation and With a Second CFTR Mutation That Is Not Likely to Respond to VX-661 and/or Ivacaftor Therapy (F508del/NR)
Study to evaluate the efficacy of VX-661 in combination with ivacaftor (IVA, VX-770) through Week 12 in participants with cystic fibrosis (CF) who are heterozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene and with a second CFTR mutation that is not likely to respond to VX-661 and/or IVA therapy (F508del/not responsive [NR]).
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
168
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
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Chermside, Australia
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Herston, Australia
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Innsbruck, Australia
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Westmead, Australia
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Queensland
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Brisban, Queensland, Australia
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Graz, Austria
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Innsbruck, Austria
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Salzburg, Austria
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Montreal, Canada
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British Columbia
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Vancouver, British Columbia, Canada
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Bron Cedex, France
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Montpellier Cedex 5, France
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Paris, France
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Paris Cedex 14, France
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Paris Cedex 19, France
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Haifa, Israel
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Hashomer, Israel
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Jerusalem, Israel
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Petah Tikva, Israel
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Barcelona, Spain
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Valencia, Spain
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Alabama
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Birmingham, Alabama, United States
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California
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La Jolla, California, United States
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Los Angeles, California, United States
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Colorado
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Denver, Colorado, United States
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Florida
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Miami, Florida, United States
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Georgia
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Atlanta, Georgia, United States
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Illinois
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Chicago, Illinois, United States
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Indiana
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Indianapolis, Indiana, United States
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Louisiana
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New Orleans, Louisiana, United States
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Michigan
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Ann Arbor, Michigan, United States
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Detroit, Michigan, United States
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Minnesota
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Minneapolis, Minnesota, United States
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Missouri
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Kansas City, Missouri, United States
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Nebraska
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Omaha, Nebraska, United States
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New York
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New York, New York, United States
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Ohio
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Cincinnati, Ohio, United States
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Tennessee
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Memphis, Tennessee, United States
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Texas
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Austin, Texas, United States
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Dallas, Texas, United States
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Virginia
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Richmond, Virginia, United States
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Washington
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Seattle, Washington, United States
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Spokane, Washington, United States
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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 and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Confirmed diagnosis of CF defined as a sweat chloride value greater than or equal to (>=)60 millimole per liter (mmol/L) by quantitative pilocarpine iontophoresis.
- Heterozygous for the F508del-CFTR mutation and with a second CFTR mutation that is not likely to respond to VX-661 and/or ivacaftor therapy, genotype to be confirmed via assessment at the Screening Visit.
- Forced Expiratory Volume in 1 Second (FEV1) >=40 percent (%) and less than or equal to (<=)90% of predicted normal for age, sex, and height at Screening Visit.
Exclusion Criteria:
- History of any comorbidity 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.
- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug).
- History of solid organ or hematological transplantation.
- Ongoing or prior participation in an investigational drug study or use of commercially available CFTR modulator within 30 days of screening.
- Pregnant or nursing females.
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: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: VX-661/IVA
VX-661 100 milligram (mg) plus IVA 150 mg fixed dose combination (FDC) tablet administered orally in the morning and IVA 150 mg film-coated tablet administered orally in the evening up to Week 12.
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Other Names:
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Placebo Comparator: Placebo
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA film-coated tablet administered orally in the evening up to Week 12.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12
Time Frame: Baseline, Through Week 12
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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, 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.
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Baseline, Through Week 12
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12
Time Frame: Baseline, Through Week 12
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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), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
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Baseline, Through Week 12
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Number of Pulmonary Exacerbation Events
Time Frame: Baseline through Week 12
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Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
The number of events were reported.
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Baseline through Week 12
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Number of Pulmonary Exacerbation Events Per Year
Time Frame: Baseline through Week 12
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Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Total number of days on study is equal to the Week 12 date or the last dose date (whichever occurs last) minus first dose date plus 1.
The total number of years (48 weeks) on study is equal to the total number of days on study divided by 336.
Pulmonary exacerbation events per year (48 weeks) are reported.
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Baseline through Week 12
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Absolute Change From Baseline in Body Mass Index (BMI) at Week 12
Time Frame: Baseline, Week 12
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BMI was defined as weight in kilogram (kg) divided by height*height in square meter (m^2).
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Baseline, Week 12
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Relative Change From Baseline in Percent Predicted FEV1 Through Week 12
Time Frame: Baseline, Through Week 12
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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, 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.
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Baseline, Through Week 12
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Absolute Change From Baseline in Sweat Chloride Through Week 12
Time Frame: Baseline, Through Week 12
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Sweat samples were collected using an approved collection device.
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Baseline, Through Week 12
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Number of Participants With at Least One Pulmonary Exacerbation Through Week 12
Time Frame: Baseline through Week 12
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Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Time-to-first pulmonary exacerbation was planned to be estimated using Kaplan-Meier (KM) estimates.
However, due to less than 50% of events, time-to-first event data was not estimated.
Instead, number of participants with at least one pulmonary exacerbation event were collected and are reported.
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Baseline through Week 12
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Absolute Change From Baseline in BMI Z-score at Week 12 (in Participants Less Than [<] 20 Years Old at the Time of Screening)
Time Frame: Baseline, Week 12
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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; where 0: same mean, >0: a greater mean, and <0: a lesser mean than the standard.
BMI, adjusted for age and sex, was analyzed as BMI-for-age Z-score (BMI z-score).
BMI-for-age z-score was calculated by using centers for disease control and prevention (CDC) growth charts for the paediatric population.
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Baseline, Week 12
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Absolute Change From Baseline in Body Weight at Week 12
Time Frame: Baseline, Week 12
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Baseline, Week 12
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Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Baseline up to Week 16
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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, inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event.
Any AE that increased in severity or newly developed at or after initial dosing of study drug to Week 16 was considered treatment-emergent.
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Baseline up to Week 16
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Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolite (M1 VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
Time Frame: Pre-morning dose on Week 2, Week 4, Week 8 and Week 12
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This outcome was not planned to be assessed in Placebo arm.
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Pre-morning dose on Week 2, Week 4, Week 8 and Week 12
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
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.
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
August 1, 2015
Primary Completion (Actual)
June 7, 2016
Study Completion (Actual)
June 7, 2016
Study Registration Dates
First Submitted
July 28, 2015
First Submitted That Met QC Criteria
August 3, 2015
First Posted (Estimate)
August 5, 2015
Study Record Updates
Last Update Posted (Actual)
June 12, 2018
Last Update Submitted That Met QC Criteria
May 8, 2018
Last Verified
May 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- VX14-661-107
- 2014-004787-37 (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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