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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02709109
Recruitment Status : Completed
First Posted : March 15, 2016
Results First Posted : July 29, 2021
Last Update Posted : July 29, 2021
Sponsor:
Collaborator:
Vertex Pharmaceuticals Incorporated
Information provided by (Responsible Party):
Parion Sciences

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

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: VX-371 + HS Drug: Hypertonic saline Drug: Placebo Drug: Orkambi Drug: VX-371 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 147 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : February 2016
Actual Primary Completion Date : September 2017
Actual Study Completion Date : September 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis
Drug Information available for: Ivacaftor

Arm Intervention/treatment
Experimental: Sequence 1: VX-371 + Hypertonic Saline (HS), then HS
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.
Drug: VX-371 + HS
Drug: Hypertonic saline
Drug: Orkambi
Other Name: lumacaftor/ivacaftor

Experimental: Sequence 2: HS, then VX-371 + HS
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.
Drug: VX-371 + HS
Drug: Hypertonic saline
Drug: Orkambi
Other Name: lumacaftor/ivacaftor

Experimental: Sequence 3: VX-371 + Placebo, then Placebo
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.
Drug: Placebo
Drug: Orkambi
Other Name: lumacaftor/ivacaftor

Drug: VX-371
Experimental: Sequence 4: Placebo, then VX-371 + Placebo
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.
Drug: Placebo
Drug: Orkambi
Other Name: lumacaftor/ivacaftor

Drug: VX-371



Primary Outcome Measures :
  1. Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs [ Time Frame: Baseline (Day 1) up to 28 days post last administration of study drug (up to 112 days) ]
    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.

  2. Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 28 [ Time Frame: Study baseline, 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 :
  1. 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 ]
  2. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02709109


Locations
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United States, Arkansas
Little Rock, Arkansas, United States
United States, California
Oakland, California, United States
United States, Florida
Gainesville, Florida, United States
Miami, Florida, United States
Orlando, Florida, United States
United States, Illinois
Chicago, Illinois, United States
Glenview, Illinois, United States
United States, Kansas
Kansas City, Kansas, United States
United States, Louisiana
New Orleans, Louisiana, United States
United States, Massachusetts
Worcester, Massachusetts, United States
United States, Michigan
Detroit, Michigan, United States
Grand Rapids, Michigan, United States
United States, Minnesota
Minneapolis, Minnesota, United States
United States, Mississippi
Jackson, Mississippi, United States
United States, New Hampshire
Lebanon, New Hampshire, United States
United States, New Mexico
Albuquerque, New Mexico, United States
United States, New York
Albany, New York, United States
Hawthorne, New York, United States
Syracuse, New York, United States
United States, North Carolina
Charlotte, North Carolina, United States
United States, Ohio
Cleveland, Ohio, United States
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States
United States, Texas
Austin, Texas, United States
Dallas, Texas, United States
Fort Worth, Texas, United States
Tyler, Texas, United States
United States, Virginia
Charlottesville, Virginia, United States
Richmond, Virginia, United States
United States, Wisconsin
Madison, Wisconsin, United States
Milwaukee, Wisconsin, United States
France
Bron Cedex, France
Pierre-Bénite, France
Roscoff Cedex, France
Strasbourg Cedex 2, France
Ireland
Dublin, Ireland
United Kingdom
Birmingham, United Kingdom
Bristol, United Kingdom
London, United Kingdom
Manchester, United Kingdom
Southampton, United Kingdom
Sponsors and Collaborators
Parion Sciences
Vertex Pharmaceuticals Incorporated
Investigators
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Study Chair: Alison Church, MD Parion Sciences
  Study Documents (Full-Text)

Documents provided by Parion Sciences:
Study Protocol  [PDF] July 22, 2016
Statistical Analysis Plan  [PDF] July 27, 2017

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Responsible Party: Parion Sciences
ClinicalTrials.gov Identifier: NCT02709109    
Other Study ID Numbers: VX15-371-101
2015-004841-13 ( EudraCT Number )
First Posted: March 15, 2016    Key Record Dates
Results First Posted: July 29, 2021
Last Update Posted: July 29, 2021
Last Verified: July 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Ivacaftor
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action