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

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03150719
• Other study ID #: VX16-661-114
• Secondary ID: 2017-000540-18
• Status: Completed
• Phase: Phase 3
• Start date: May 24, 2017
• Est. completion date: August 9, 2018

Study information

• Verified date: September 2019
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: August 9, 2018
• Est. primary completion date: August 9, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Tezacaftor/Ivacaftor
TEZ 100 mg/IVA 150 mg fixed-dose combination tablet.
• Ivacaftor
IVA 150 mg tablet.
• Placebo
Placebo matched to TEZ/IVA fixed-dose combination tablet.
• Placebo
Placebo matched to IVA tablet.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  France,  Germany, 

Outcome

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