Clinical trial NCT03150719: A Study to Evaluate Safety, Efficacy, and Tolerability of TEZ/IVA in Orkambi® (Lumacaftor/Ivacaftor) -Experienced Subjects With Cystic Fibrosis (CF)
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2017-05-12
Enrollment: 98
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Respiratory Adverse Events of Special Interest (RAESIs)
timeFrame: Day 1 up to Day 84
Secondary outcomes:
measure: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Day 28 and Day 56 Measurements
timeFrame: Baseline, Day 28 and Day 56
measure: Relative Change From Baseline in ppFEV1 at Average of Day 28 and Day 56 Measurements
timeFrame: Baseline, Day 28 and Day 56
measure: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Day 28 and Day 56 Measurements
timeFrame: Baseline, Day 28 and Day 56
measure: Tolerability as Assessed by Number of Participants Who Discontinued Treatment
timeFrame: Day 1 through Day 56
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Day 84
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Fresno
country: United States
facility: UCSF - Fresno, Community Regional Medical Center
state: California
city: Long Beach
country: United States
facility: Miller Children's Hospital / Long Beach Memorial
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Orlando
country: United States
facility: Central Florida Pulmonary Group
state: Florida
city: Orlando
country: United States
facility: Arnold Palmer Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital Cardiac and Lung Transplant Clinic
state: Florida
city: Atlanta
country: United States
facility: Children's Speciality Services at North Druid Hills
state: Georgia
city: Boise
country: United States
facility: St. Luke's CF Center of Idaho
state: Idaho
city: Niles
country: United States
facility: Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children at Indiana University Health
state: Indiana
city: Iowa City
country: United States
facility: The University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: Kentucky Clinic
state: Kentucky
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital Cystic Fibrosis Center
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Santiago Reyes, M.D.
state: Oklahoma
city: Philadelphia
country: United States
facility: Drexel University College of Medicine/ Drexel Adult Cystic Fibrosis Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Nashville
country: United States
facility: The University of Tennessee Medical Center
state: Tennessee
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah / Primary Children's Medical Center
state: Utah
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Richmond
country: United States
facility: Children's Hospital of Richmond at VCU, Children's Pavilion
state: Virginia
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal de Créteil
city: Grenoble
country: France
facility: Centre Hospitalier Universitaire De Grenoble - Hopital Michallon
city: Montpellier Cedex 5
country: France
facility: CHU de Montpellier - Hopital Arnaud de Villeneuve
city: Nantes
country: France
facility: Centre Hospitalier Universitaire De Nantes
city: Nice
country: France
facility: Centre hospitalier universitaire de Nice, Pulmonology
city: Paris Cedex 14
country: France
facility: Hopital Cochin
city: Rouen
country: France
facility: Centre Hospitalier Universitaire - Hopitaux de Rouen
city: Berlin
country: Germany
facility: Charite Paediatric Pulmonology Department
city: Essen
country: Germany
facility: Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
city: Muenchen
country: Germany
facility: Klinikum Innenstadt, University of Munich
city: Muenchen
country: Germany
facility: Pneumologische Praxis Pasing
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin
Study officials:
References: