A Study to Evaluate the Safety and Efficacy of VX-371 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2015-004841-13-GB
• Date of registration: 09/06/2016
• Prospective Registration: Yes
• Primary sponsor: Vertex Pharmaceuticals, Inc.
• Public title: A Study to Evaluate the Safety and Efficacy of VX-371 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation
• Scientific title: A Phase 2a, Randomized, Double-blind, Placebo-controlled, Incomplete Block, Crossover Study to Evaluate the Safety and Efficacy of VX-371 in Subjects Aged 12 Years or Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation, and Being Treated With Orkambi
• Date of first enrolment: 20/07/2016
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004841-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: yes; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, France, Ireland, United Kingdom, United States

Contacts

• Name: Clinical Trials and Medical Info.
• Affiliation: Vertex Pharmaceuticals, Inc.

• Name: Clinical Trials and Medical Info.
• Affiliation: Vertex Pharmaceuticals, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
•Willing and able to use the delivery device as directed by the study manual
•Confirmed diagnosis of CF, defined as a sweat chloride value =60 mmol/L by quantitative pilocarpine iontophoresis.
•Homozygous for the F508del CFTR mutation. If the CFTR screening genotype result is not received before randomization, a previous CFTR genotype lab report may be used to establish eligibility.
•Percent predicted FEV1 of =40 to <90 percentage points adjusted for age, sex, and height according to the Global Lung Initiative (GLI) at the Screening Visit.
•Willing to discontinue physician-prescribed HS use.
•Female subjects of childbearing potential with a negative serum pregnancy test at the Screening Visit
Are the trial subjects under 18? yes
Number of subjects for this age range: 35
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 115
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
•History of any comorbidity, which 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.
•Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject.
•An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug).
•A 12 lead ECG demonstrating QTcF >450 msec at the Screening Visit.
•History of solid organ or hematological transplantation.
•Used diuretics or renin-angiotensin aldosterone system antihypertensive drugs in the 28 days prior to Screening or an anticipated need for any of these medications during the study.
•Ongoing or prior participation in an investigational drug study within 30 days of the Screening Visit.
•Inability to withhold short-acting, long-acting, or once-daily, long-acting bronchodilator use for 4, 12, or 24 hours prior to clinic visit, respectively.
•History of significant intolerance to inhaled HS, or intolerance to the single dose of HS at Screening
•Known hypersensitivity or history of intolerance to Orkambi.
•Pregnant and nursing females.
•Subjects who have participated in Parion Sciences Study PS-G201.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Cystic Fibrosis
MedDRA version: 20.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Code: VX-371 in hypertonic saline
Pharmaceutical Form: Inhalation solution
INN or Proposed INN: Not yet assigned
Current Sponsor code: VX-371
Other descriptive name: VX-371
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: up to
Concentration number: 30-

Product Code: VX-371 in saline
Pharmaceutical Form: Inhalation solution
INN or Proposed INN: Not yet assigned
Current Sponsor code: VX-371
Other descriptive name: VX-371
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: up to
Concentration number: 30-
Pharmaceutical form of the placebo: Inhalation solution
Route of administration of the placebo: Inhalation use

Trade Name: Orkambi
Product Name: lumacaftor/ivacaftor 200mg/125mg
Product Code: VX-809/VX-770
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: IVACAFTOR
CAS Number: 873054-44-5
Current Sponsor code: VX-770
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
INN or Proposed INN: Lumacaftor
CAS Number: 936727-05-8
Current Sponsor code: VX-809
Other descriptive name: LUMACAFTOR
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Product Name: Hypertonic saline
Pharmaceutical Form: Inhalation solution
INN or Proposed INN: 4.2% NaCl/Inhalation solution
Current Sponsor code: 4.2% NaCl/Inhalation solution

Primary Outcome(s)

Primary end point(s): •Results of safety and tolerability assessments of adverse events (AEs), spirometry, clinical laboratory values (urine, serum and plasma chemistry, hematology and coagulation studies), standard 12-lead electrocardiograms (ECGs), vital signs, and ophthalmologic examinations
•Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1)

Timepoint(s) of evaluation of this end point: •Safety from baseline up to 28 days post last administration of study drug, up to 12 Weeks.
•Efficacy from study baseline at Day 28 in each Treatment Period

Secondary Objective: To investigate the pharmacokinetics (PK) of VX-371 in subjects with CF who are =12 years of age, homozygous for the F508del-CFTR mutation, and being treated with Orkambi

Main Objective: To evaluate the safety and efficacy of treatment with VX-371 in hypertonic saline (HS) compared to HS alone in subjects with cystic fibrosis (CF) who are =12 years of age, homozygous for the F508del-CFTR mutation, and being treated with Orkambi

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: •From study baseline at Day 28 in each Treatment Period

Secondary end point(s): •PK parameters for VX-371

Secondary ID(s)

2015-004841-13-IE

VX15-371-101

Source(s) of Monetary Support

Vertex Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 29/04/2018
• Date Completed: 12/10/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-004841-13/results