Clinical trial NCT02951182: A Study Evaluating the Safety and Efficacy of VX-440 Combination Therapy in Subjects With Cystic Fibrosis
Official title: A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of VX-440 Combination Therapy in Subjects Aged 12 Years and Older With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2016-11-01
Enrollment: 74
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: This is a Phase 2, randomized, double-blind, placebo- and active-controlled, parallel group, multicenter study to evaluate the safety, tolerability, and efficacy of VX-440 in dual and triple combination with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F508del/F508del), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF).


Eligibility criteria: Inclusion Criteria:

* Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
* To prevent pregnancy, female participants of childbearing potential and their male partners will be required to use pre-specified, highly effective methods of non-hormonal contraception. Male participants with female partners of childbearing potential will be required to use a condom.
* Body weight ≥35 kg.
* Sweat chloride value ≥60 mmol/L from test results obtained during screening.
* Subjects must have an eligible CFTR genotype:

  * Heterozygous for F508del and a minimal function (MF) mutation known or predicted not to be responsive to TEZ and/or IVA.
  * Homozygous for F508del
* Subjects must have an FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height at the Screening Visit
* Stable CF disease as judged by the investigator.
* Willing to remain on a stable CF medication regimen through the planned end of treatment or, if applicable, the Safety Follow up 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 subject.
* History of cirrhosis with portal hypertension.
* Risk factors for Torsade de Pointes
* History of hemolysis.
* Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.
* Clinically significant abnormal laboratory values at screening
* An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before the first dose of study drug.
* Lung infection with organisms associated with a more rapid decline in pulmonary status
* An acute illness not related to CF within 14 days before the first dose of study drug
* A standard digital ECG demonstrating QTc \>450 msec at screening.
* History of solid organ or hematological transplantation.
* History or evidence of cataract or lens opacity determined to be clinically significant by the ophthalmologist or optometrist based on the ophthalmologic examination during the Screening Period.
* History of alcohol or drug abuse in the past year, including but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator.
* Ongoing or prior participation in an investigational drug study, with certain exceptions. (e.g., ongoing participation in NCT02565914)
* Use of commercially available CFTR modulator (e.g., Kalydeco, Orkambi) within 14 days before screening (applies only to the Heterozygous F508del/MF cohorts; does not apply to the Homozygous F508del/F508del Cohort).
* Pregnant or nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1.

Primary outcomes:
measure: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose of Study Drug in the Treatment Period through Safety Follow-up Visit (Up to Day 57 for Part 1 and Day 85 for Part 2)
measure: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
timeFrame: From Baseline through Day 29
Secondary outcomes:
measure: Absolute Change in Sweat Chloride Concentrations
timeFrame: From Baseline through Day 29
measure: Relative Change in ppFEV1
timeFrame: From Baseline through Day 29
measure: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
timeFrame: From Baseline at Day 29
measure: Pre-dose Plasma Concentration (Ctrough) of VX-440, TEZ, M1-TEZ, IVA and M1-IVA
timeFrame: Predose at Day 8, Day 15 and Day 29
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The Arizona Board of Regents on behalf of the University of Arizona
state: Arizona
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Francisco
country: United States
facility: University of California
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Hollywood
country: United States
facility: Joe Di Maggio Cystic Fibrosis & Pulmonary Center
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group
state: Florida
city: Boise
country: United States
facility: St. Luke's CF Center of Idaho
state: Idaho
city: Glenview
country: United States
facility: Cystic Fibrosis Center of Chicago
state: Illinois
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital Cystic Fibrosis Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Hawthorne
country: United States
facility: New York Medical College
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Respiratory Diseases of Children and Adolescents
state: Oklahoma
city: Pittsburgh
country: United States
facility: UPMC OSPARS Children's Hospital of Pittsburgh
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Children's Specialty Clinic Sanford Research USD
state: South Dakota
city: Dallas
country: United States
facility: The University of Texas Southwestern Center
state: Texas
city: Norfolk
country: United States
facility: Children's Hospital of the Kings Daughters
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Chermside
country: Australia
facility: Prince Charles Hospital
city: New Lambton Heights
country: Australia
facility: John Hunter Hospital & Hunter Medical Research Institute
city: Innsbruck
country: Austria
facility: Medizinische Universitat Innsbruck
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
city: Vancouver
country: Canada
facility: St. Paul's Hopsital
state: British Columbia
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Copenhagen
country: Denmark
facility: Juliane Marie Center, Righospitalet
city: Jena
country: Germany
facility: Mukeviszidose-Zentrum am Universtitatsklinikum Jena
city: Koeln
country: Germany
facility: University Hospital Cologne
city: Muenchen
country: Germany
facility: Pneumologische Praxis Pasing
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d´Hebron Servicio de Broncoscopia
city: Seville
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Birmingham
country: United Kingdom
facility: Heart of England NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
city: Southampton
country: United Kingdom
facility: Southampton University Hospitals NHS Foundation Trust
Study officials:
References: