A Study to Evaluate Safety, Efficacy, and Tolerability of TEZ/IVA in Orkambi® (Lumacaftor/Ivacaftor) -Experienced Subjects With Cystic Fibrosis (CF)
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
2 other identifiers
interventional
98
3 countries
53
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started May 2017
Shorter than P25 for phase_3
53 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 3, 2017
CompletedFirst Posted
Study publicly available on registry
May 12, 2017
CompletedStudy Start
First participant enrolled
May 24, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 9, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
August 9, 2018
CompletedResults Posted
Study results publicly available
September 12, 2019
CompletedSeptember 12, 2019
September 1, 2019
1.2 years
May 3, 2017
August 8, 2019
September 11, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of Respiratory Adverse Events of Special Interest (RAESIs)
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 Outcomes (5)
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Day 28 and Day 56 Measurements
Baseline, Day 28 and Day 56
Relative Change From Baseline in ppFEV1 at Average of Day 28 and Day 56 Measurements
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
Baseline, Day 28 and Day 56
Tolerability as Assessed by Number of Participants Who Discontinued Treatment
Day 1 through Day 56
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Day 1 up to Day 84
Study Arms (2)
Placebo
PLACEBO COMPARATORParticipants 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.
TEZ/IVA
EXPERIMENTALParticipants 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.
Interventions
TEZ 100 mg/IVA 150 mg fixed-dose combination tablet.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (53)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
Phoenix Children's Hospital
Phoenix, Arizona, 85016, United States
UCSF - Fresno, Community Regional Medical Center
Fresno, California, 93701, United States
Miller Children's Hospital / Long Beach Memorial
Long Beach, California, 90806, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Rady Children's Hospital
San Diego, California, 92123, United States
National Jewish Health
Denver, Colorado, 80206, United States
Yale New Haven Hospital
New Haven, Connecticut, 06510, United States
Central Florida Pulmonary Group
Orlando, Florida, 32803, United States
Arnold Palmer Hospital
Orlando, Florida, 32806, United States
Tampa General Hospital Cardiac and Lung Transplant Clinic
Tampa, Florida, 33606, United States
Children's Speciality Services at North Druid Hills
Atlanta, Georgia, 30324, United States
St. Luke's CF Center of Idaho
Boise, Idaho, 83702, United States
Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants
Niles, Illinois, 60714, United States
Southern Illinois University
Springfield, Illinois, 62702, United States
Riley Hospital for Children at Indiana University Health
Indianapolis, Indiana, 46202, United States
The University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
Kentucky Clinic
Lexington, Kentucky, 40536, United States
Tulane Medical Center
New Orleans, Louisiana, 70112, United States
Massachusetts General Hospital Cystic Fibrosis Center
Boston, Massachusetts, 02114, United States
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Children's Mercy Hospital
Kansas City, Missouri, 64108, United States
Billings Clinic
Billings, Montana, 59101, United States
Mount Sinai Beth Israel
New York, New York, 10003, United States
New York Medical College
Valhalla, New York, 10595, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, 27157, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Santiago Reyes, M.D.
Oklahoma City, Oklahoma, 73112, United States
Drexel University College of Medicine/ Drexel Adult Cystic Fibrosis Center
Philadelphia, Pennsylvania, 19107, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
The University of Tennessee Medical Center
Nashville, Tennessee, 37920, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723, United States
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78207, United States
University of Utah / Primary Children's Medical Center
Salt Lake City, Utah, 84132, United States
Children's Hospital of the King's Daughters
Norfolk, Virginia, 23507, United States
Children's Hospital of Richmond at VCU, Children's Pavilion
Richmond, Virginia, 23298, United States
Centre Hospitalier Intercommunal de Créteil
Créteil, France
Centre Hospitalier Universitaire De Grenoble - Hopital Michallon
Grenoble, France
CHU de Montpellier - Hopital Arnaud de Villeneuve
Montpellier, France
Centre Hospitalier Universitaire De Nantes
Nantes, France
Centre hospitalier universitaire de Nice, Pulmonology
Nice, France
Hopital Cochin
Paris, France
Centre Hospitalier Universitaire - Hopitaux de Rouen
Rouen, France
Charite Paediatric Pulmonology Department
Berlin, Germany
Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
Essen, Germany
Klinikum Innenstadt, University of Munich
München, Germany
Pneumologische Praxis Pasing
München, Germany
Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin
Tübingen, Germany
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Monitor
- Organization
- Vertex Pharmaceuticals Incorporated
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
May 3, 2017
First Posted
May 12, 2017
Study Start
May 24, 2017
Primary Completion
August 9, 2018
Study Completion
August 9, 2018
Last Updated
September 12, 2019
Results First Posted
September 12, 2019
Record last verified: 2019-09