A Study to Evaluate Safety, Efficacy, and Tolerability of TEZ/IVA in Orkambi® (Lumacaftor/Ivacaftor) -Experienced Subjects With Cystic Fibrosis (CF)

September 11, 2019 updated by: Vertex Pharmaceuticals Incorporated

Phase 3b, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Safety, Efficacy, and Tolerability of Tezacaftor/Ivacaftor (TEZ/IVA) in an Orkambi-experienced Population Who Are Homozygous for the F508del CFTR Mutation

Study VX16-661-114 (Study 114) is a Phase 3b, randomized, double-blind, placebo-controlled, parallel-group, multicenter study in subjects aged 12 years and older with CF who are homozygous for the F508del mutation on the cystic fibrosis transmembrane conductance regulator gene (CFTR) gene and who discontinued treatment with Orkambi due to respiratory symptoms considered related to treatment. This study is designed to evaluate the safety and efficacy of Tezacaftor/Ivacaftor (TEZ/IVA).

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.
98

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 3

Expanded Access

Expanded Access

A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved by the U.S. Food and Drug Administration (FDA). Also called compassionate use. There are different expanded access types.
Approved

Approved

  • Available: Expanded access is currently available for this investigational treatment, and patients who are not participants in the clinical study may be able to gain access to the drug, biologic, or medical device being studied.
  • No longer available: Expanded access was available for this intervention previously but is not currently available and will not be available in the future.
  • Temporarily not available: Expanded access is not currently available for this intervention but is expected to be available in the future.
  • Approved for marketing: The intervention has been approved by the U.S. Food and Drug Administration for use by the public.
 for sale to the public. See expanded access record.

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

  • France
      • Créteil, France
        • Centre Hospitalier Intercommunal de Créteil
      • Grenoble, France
        • Centre Hospitalier Universitaire de Grenoble - Hôpital Michallon
      • Montpellier Cedex 5, France
        • CHU de Montpellier - Hôpital Arnaud de Villeneuve
      • Nantes, France
        • Centre Hospitalier Universitaire de Nantes
      • Nice, France
        • Centre hospitalier universitaire de Nice, Pulmonology
      • Paris Cedex 14, France
        • Hopital Cochin
      • Rouen, France
        • Centre Hospitalier Universitaire - Hopitaux de Rouen
  • Germany
      • Berlin, Germany
        • Charite Paediatric Pulmonology Department
      • Essen, Germany
        • Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
      • Muenchen, Germany
        • Pneumologische Praxis Pasing
      • Muenchen, Germany
        • Klinikum Innenstadt, University of Munich
      • Tuebingen, Germany
        • Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Phoenix Children's Hospital
    • California
      • Fresno, California, United States, 93701
        • UCSF - Fresno, Community Regional Medical Center
      • Long Beach, California, United States, 90806
        • Miller Children's Hospital / Long Beach Memorial
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
      • San Diego, California, United States, 92123
        • Rady Children's Hospital
    • Colorado
      • Denver, Colorado, United States, 80206
        • National Jewish Health
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale New Haven Hospital
    • Florida
      • Orlando, Florida, United States, 32803
        • Central Florida Pulmonary Group
      • Orlando, Florida, United States, 32806
        • Arnold Palmer Hospital
      • Tampa, Florida, United States, 33606
        • Tampa General Hospital Cardiac and Lung Transplant Clinic
    • Georgia
      • Atlanta, Georgia, United States, 30324
        • Children's Speciality Services at North Druid Hills
    • Idaho
      • Boise, Idaho, United States, 83702
        • St. Luke's CF Center of Idaho
    • Illinois
      • Niles, Illinois, United States, 60714
        • Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children at Indiana University Health
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • The University of Iowa Hospitals and Clinics
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Kentucky Clinic
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cystic Fibrosis Center
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospital
    • Montana
      • Billings, Montana, United States, 59101
        • Billings Clinic
    • New York
      • New York, New York, United States, 10003
        • Mount Sinai Beth Israel
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Baptist Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
      • Oklahoma City, Oklahoma, United States, 73112
        • Santiago Reyes, M.D.
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Drexel University College of Medicine/ Drexel Adult Cystic Fibrosis Center
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
      • Nashville, Tennessee, United States, 37920
        • The University of Tennessee Medical Center
    • Texas
      • Austin, Texas, United States, 78723
        • Dell Children's Medical Center of Central Texas
      • San Antonio, Texas, United States, 78207
        • The University of Texas Health Science Center at San Antonio
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah / Primary Children's Medical Center
    • Virginia
      • Norfolk, Virginia, United States, 23507
        • Children's Hospital of The King's Daughters
      • Richmond, Virginia, United States, 23298
        • Children's Hospital of Richmond at VCU, Children's Pavilion

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

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
  • Prior discontinuation of Orkambi, with at least 1 respiratory sign or symptom considered related to therapy.
  • Resolution or stabilization of qualifying event(s) >28 days prior to Screening.
  • Discontinuation of Orkambi therapy must have occurred within approximately 12 weeks from the first dose of Orkambi.
  • Homozygous for F508del mutation in the CFTR gene as documented in the subject's medical record. If genotype documentation is not available in the medical record, genotyping will be performed during screening.
  • FEV1 ≥25% and ≤90% of predicted normal for age, sex, and height.
  • Stable CF disease as judged by the investigator.
  • Other protocol defined inclusion criteria could apply.

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 subject.
  • Recent rapid or progressive deterioration in respiratory status.
  • Receiving continuous oxygen at >2L/min or on face-mask ventilation.
  • Any protocol-defined exclusionary laboratory values at Screening.
  • Child-Pugh Class B or C hepatic impairment.
  • An acute upper or lower respiratory infection, pulmonary exacerbation, or change in therapy for pulmonary disease within 28 days before Day 1.
  • Documentation of colonization with organisms associated with a more rapid decline in pulmonary status.
  • History of lung transplantation since most recent initiation of Orkambi.
  • History of alcohol or drug abuse in the past year as deemed by the investigator.
  • Participation in an investigational drug study or use of a CFTR modulator within 28 days or 5 terminal half-lives of the investigational drug or modulator (whichever is longer).
  • Use of restricted medications or foods within the specified window before the first dose of study drug, or an anticipated need or use of restricted medication or foods after the first dose of study drug.
  • Pregnant or nursing females: Females of child-bearing potential must have a negative pregnancy test at Screening and Day 1.
  • Other protocol defined exclusion criteria could apply.

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: Quadruple

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: Placebo
Participants received placebo matched to TEZ/IVA fixed-dose combination tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 56 days.
Drug: Placebo
Placebo matched to TEZ/IVA fixed-dose combination tablet.
Drug: Placebo
Placebo matched to IVA tablet.
Experimental: TEZ/IVA
Participants received TEZ 100 milligram (mg)/IVA 150 mg fixed-dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 56 days.
Drug: Tezacaftor/Ivacaftor
TEZ 100 mg/IVA 150 mg fixed-dose combination tablet.
Other Names:
  • TEZ/IVA; VX-661/VX-770
Drug: Ivacaftor
IVA 150 mg 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
Incidence of Respiratory Adverse Events of Special Interest (RAESIs)
Time Frame: Day 1 up to Day 84
RAESIs included chest discomfort, dyspnea (shortness of breath), respiration abnormal (chest tightness), asthma, bronchial hyperreactivity, bronchospasm, and wheezing.
Day 1 up to Day 84

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
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Day 28 and Day 56 Measurements
Time Frame: Baseline, Day 28 and Day 56
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Baseline, Day 28 and Day 56
Relative Change From Baseline in ppFEV1 at Average of Day 28 and Day 56 Measurements
Time Frame: Baseline, Day 28 and Day 56
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Baseline, Day 28 and Day 56
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Day 28 and Day 56 Measurements
Time Frame: Baseline, Day 28 and Day 56
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 indicating fewer symptoms and better health-related quality of life.
Baseline, Day 28 and Day 56
Tolerability as Assessed by Number of Participants Who Discontinued Treatment
Time Frame: Day 1 through Day 56
Day 1 through Day 56
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Day 1 up to Day 84
Day 1 up to Day 84

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

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 (Actual)

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.
May 24, 2017

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.
August 9, 2018

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.
August 9, 2018

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).
May 3, 2017

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.
May 9, 2017

First Posted (Actual)

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.
May 12, 2017

Study Record Updates

Last Update Posted (Actual)

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.
September 12, 2019

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 11, 2019

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, 2019

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.
  • VX16-661-114
  • 2017-000540-18 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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