A Study Evaluating the Safety and Efficacy of VX-440 Combination Therapy in Subjects With Cystic Fibrosis

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02951182
• Other study ID #: VX15-440-101
• Secondary ID: 2016-000454-36
• Status: Completed
• Phase: Phase 2
• Start date: October 2016
• Est. completion date: August 2017

Study information

• Verified date: August 2020
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: August 2017
• Est. primary completion date: August 2017
• 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.

• 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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• TEZ

• IVA

• VX-440

• Matched Placebo

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	Prince Charles Hospital	Chermside
Australia	John Hunter Hospital & Hunter Medical Research Institute	New Lambton Heights
Austria	Medizinische Universitat Innsbruck	Innsbruck
Belgium	Universitair Ziekenhuis Brussel	Brussels
Belgium	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	St. Paul's Hopsital	Vancouver	British Columbia
Denmark	Juliane Marie Center, Righospitalet	Copenhagen
Germany	Mukeviszidose-Zentrum am Universtitatsklinikum Jena	Jena
Germany	University Hospital Cologne	Koeln
Germany	Pneumologische Praxis Pasing	Muenchen
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Spain	Hospital Universitari Vall d´Hebron Servicio de Broncoscopia	Barcelona
Spain	Hospital Universitario Virgen del Rocio	Seville
United Kingdom	Heart of England NHS Foundation Trust	Birmingham
United Kingdom	Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital	London
United Kingdom	Southampton University Hospitals NHS Foundation Trust	Southampton
United States	The Johns Hopkins Hospital	Baltimore	Maryland
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	Nationwide Children's Hospital	Columbus	Ohio
United States	The University of Texas Southwestern Center	Dallas	Texas
United States	National Jewish Health	Denver	Colorado
United States	Cystic Fibrosis Center of Chicago	Glenview	Illinois
United States	New York Medical College	Hawthorne	New York
United States	Joe Di Maggio Cystic Fibrosis & Pulmonary Center	Hollywood	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Columbia University Medical Center	New York	New York
United States	Children's Hospital of the Kings Daughters	Norfolk	Virginia
United States	Respiratory Diseases of Children and Adolescents	Oklahoma City	Oklahoma
United States	Central Florida Pulmonary Group	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	UPMC OSPARS Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of California	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Sanford Children's Specialty Clinic Sanford Research USD	Sioux Falls	South Dakota
United States	The Arizona Board of Regents on behalf of the University of Arizona	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Denmark,  Germany,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)		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)
Primary	Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	From Baseline through Day 29
Secondary	Absolute Change in Sweat Chloride Concentrations	Sweat samples were collected using an approved collection device.	From Baseline through Day 29
Secondary	Relative Change in ppFEV1	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	From Baseline through Day 29
Secondary	Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score	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.	From Baseline at Day 29
Secondary	Pre-dose Plasma Concentration (Ctrough) of VX-440, TEZ, M1-TEZ, IVA and M1-IVA		Predose at Day 8, Day 15 and Day 29