Clinical trial NCT02709109: A Study to Evaluate the Safety and Efficacy of VX-371 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Parion Sciences
Sponsor class: INDUSTRY
Collaborators: name: Vertex Pharmaceuticals Incorporated
First posted: 2016-03-15
Enrollment: 147
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficacy of treatment with VX-371 in hypertonic saline compared to hypertonic saline alone in subjects with cystic fibrosis (CF) who are ≥12 years of age, homozygous for the F508del-cystic fibrosis transmembrane conductance regulator (CFTR) mutation, and being treated with Orkambi


Eligibility 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 forced expiratory volume at one second (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 saline use.
* Female subjects of childbearing potential with a negative serum pregnancy test at the Screening Visit.

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 saline, or intolerance to the single dose of saline at Screening
* Known hypersensitivity or history of intolerance to Orkambi.
* Pregnant and nursing females.
* Subjects who have participated in Parion Sciences Study NCT02343445.

Primary outcomes:
measure: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Baseline (Day 1) up to 28 days post last administration of study drug (up to 112 days)
measure: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 28
timeFrame: Study baseline, Day 28
Secondary outcomes:
measure: Plasma Concentrations of VX-371
timeFrame: Pre-dose (90 minutes prior inhaled study drug administration) and 60 minutes post-dose on Days 1, 14 and 28 within treatment period 1 and 2
measure: Urine Concentrations of VX-371
timeFrame: Pre-dose (90 minutes prior inhaled study drug administration) and 60 minutes post-dose on Days 1, 14 and 28 within treatment period 1 and 2
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Oakland
country: United States
state: California
city: Gainesville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Glenview
country: United States
state: Illinois
city: Kansas City
country: United States
state: Kansas
city: New Orleans
country: United States
state: Louisiana
city: Worcester
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Grand Rapids
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Jackson
country: United States
state: Mississippi
city: Lebanon
country: United States
state: New Hampshire
city: Albuquerque
country: United States
state: New Mexico
city: Albany
country: United States
state: New York
city: Hawthorne
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Pittsburgh
country: United States
state: Pennsylvania
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: Charlottesville
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Madison
country: United States
state: Wisconsin
city: Milwaukee
country: United States
state: Wisconsin
city: Bron Cedex
country: France
city: Pierre-Bénite
country: France
city: Roscoff Cedex
country: France
city: Strasbourg Cedex 2
country: France
city: Dublin
country: Ireland
city: Birmingham
country: United Kingdom
city: Bristol
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Southampton
country: United Kingdom
Study officials:
affiliation: Parion Sciences
name: Alison Church, MD
role: STUDY_CHAIR
References: