Back to resultsA Study to Evaluate the Safety and Efficacy of VX-371 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
VX-371 + HS
Hypertonic saline
Placebo
Orkambi
VX-371
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Sequence 1: VX-371 + Hypertonic Saline (HS), then HS
Sequence 2: HS, then VX-371 + HS
Sequence 3: VX-371 + Placebo, then Placebo
Sequence 4: Placebo, then VX-371 + Placebo
Arm Description
Participants received 85 microgram (mcg) VX-371 diluted in 3 milliliter (mL) 4.2 percent (%) HS through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 milligram (mg)/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their cystic fibrosis (CF) standard of care.
Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 mg/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their CF standard of care.
Participants received 85 mcg VX-371 diluted in 3 mL 0.17% Saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 mg/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their CF standard of care.
Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 mg/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their CF standard of care.
Outcomes
Primary Outcome Measures
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included abnormal clinically significant findings for spirometry, clinical laboratory parameters, standard 12-lead electrocardiograms (ECGs), vital signs and ophthalmologic examinations. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 112 days (up to 28 days after last dose) that were absent before treatment or that worsened relative to pretreatment state. TEAEs included both serious and non-serious TEAEs.
Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 28
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Study Baseline was defined as the most recent non-missing measurement before the first dose of inhaled study drug in the study. Day 28 measurements after treatment discontinuation from the treatment period in which discontinuation occurred were included in the analysis.
Secondary Outcome Measures
Plasma Concentrations of VX-371
Urine Concentrations of VX-371
Full Information
NCT ID
NCT02709109
First Posted
February 29, 2016
Last Updated
July 8, 2021
Sponsor
Parion Sciences
Collaborators
Vertex Pharmaceuticals Incorporated
1. Study Identification
Unique Protocol Identification Number
NCT02709109
Brief 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
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
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
February 2016 (undefined)
Primary Completion Date
September 2017 (Actual)
Study Completion Date
September 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Parion Sciences
Collaborators
Vertex Pharmaceuticals Incorporated
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
147 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sequence 1: VX-371 + Hypertonic Saline (HS), then HS
Arm Type
Experimental
Arm Description
Participants received 85 microgram (mcg) VX-371 diluted in 3 milliliter (mL) 4.2 percent (%) HS through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 milligram (mg)/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their cystic fibrosis (CF) standard of care.
Arm Title
Sequence 2: HS, then VX-371 + HS
Arm Type
Experimental
Arm Description
Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 mg/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their CF standard of care.
Arm Title
Sequence 3: VX-371 + Placebo, then Placebo
Arm Type
Experimental
Arm Description
Participants received 85 mcg VX-371 diluted in 3 mL 0.17% Saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 mg/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their CF standard of care.
Arm Title
Sequence 4: Placebo, then VX-371 + Placebo
Arm Type
Experimental
Arm Description
Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 mg/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their CF standard of care.
Intervention Type
Drug
Intervention Name(s)
VX-371 + HS
Intervention Type
Drug
Intervention Name(s)
Hypertonic saline
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Type
Drug
Intervention Name(s)
Orkambi
Other Intervention Name(s)
lumacaftor/ivacaftor
Intervention Type
Drug
Intervention Name(s)
VX-371
Primary Outcome Measure Information:
Title
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Description
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included abnormal clinically significant findings for spirometry, clinical laboratory parameters, standard 12-lead electrocardiograms (ECGs), vital signs and ophthalmologic examinations. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 112 days (up to 28 days after last dose) that were absent before treatment or that worsened relative to pretreatment state. TEAEs included both serious and non-serious TEAEs.
Time Frame
Baseline (Day 1) up to 28 days post last administration of study drug (up to 112 days)
Title
Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 28
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Study Baseline was defined as the most recent non-missing measurement before the first dose of inhaled study drug in the study. Day 28 measurements after treatment discontinuation from the treatment period in which discontinuation occurred were included in the analysis.
Time Frame
Study baseline, Day 28
Secondary Outcome Measure Information:
Title
Plasma Concentrations of VX-371
Time Frame
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
Title
Urine Concentrations of VX-371
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alison Church, MD
Organizational Affiliation
Parion Sciences
Official's Role
Study Chair
Facility Information:
City
Little Rock
State/Province
Arkansas
Country
United States
City
Oakland
State/Province
California
Country
United States
City
Gainesville
State/Province
Florida
Country
United States
City
Miami
State/Province
Florida
Country
United States
City
Orlando
State/Province
Florida
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Glenview
State/Province
Illinois
Country
United States
City
Kansas City
State/Province
Kansas
Country
United States
City
New Orleans
State/Province
Louisiana
Country
United States
City
Worcester
State/Province
Massachusetts
Country
United States
City
Detroit
State/Province
Michigan
Country
United States
City
Grand Rapids
State/Province
Michigan
Country
United States
City
Minneapolis
State/Province
Minnesota
Country
United States
City
Jackson
State/Province
Mississippi
Country
United States
City
Lebanon
State/Province
New Hampshire
Country
United States
City
Albuquerque
State/Province
New Mexico
Country
United States
City
Albany
State/Province
New York
Country
United States
City
Hawthorne
State/Province
New York
Country
United States
City
Syracuse
State/Province
New York
Country
United States
City
Charlotte
State/Province
North Carolina
Country
United States
City
Cleveland
State/Province
Ohio
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
City
Austin
State/Province
Texas
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Fort Worth
State/Province
Texas
Country
United States
City
Tyler
State/Province
Texas
Country
United States
City
Charlottesville
State/Province
Virginia
Country
United States
City
Richmond
State/Province
Virginia
Country
United States
City
Madison
State/Province
Wisconsin
Country
United States
City
Milwaukee
State/Province
Wisconsin
Country
United States
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
12. IPD Sharing Statement
Learn more about this trial
A Study to Evaluate the Safety and Efficacy of VX-371 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation
We'll reach out to this number within 24 hrs