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

NCT ID: NCT02709109

Last Updated: 2021-07-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

147 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-02-29

Study Completion Date

2017-09-30

Brief Summary

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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

Detailed Description

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Conditions

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Cystic Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

VX-371 + HS

Intervention Type DRUG

Hypertonic saline

Intervention Type DRUG

Orkambi

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

VX-371 + HS

Intervention Type DRUG

Hypertonic saline

Intervention Type DRUG

Orkambi

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Orkambi

Intervention Type DRUG

VX-371

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Orkambi

Intervention Type DRUG

VX-371

Intervention Type DRUG

Interventions

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VX-371 + HS

Intervention Type DRUG

Hypertonic saline

Intervention Type DRUG

Placebo

Intervention Type DRUG

Orkambi

Intervention Type DRUG

VX-371

Intervention Type DRUG

Other Intervention Names

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lumacaftor/ivacaftor

Eligibility Criteria

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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.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role collaborator

Parion Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alison Church, MD

Role: STUDY_CHAIR

Parion Sciences

Locations

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Little Rock, Arkansas, United States

Site Status

Oakland, California, United States

Site Status

Gainesville, Florida, United States

Site Status

Miami, Florida, United States

Site Status

Orlando, Florida, United States

Site Status

Chicago, Illinois, United States

Site Status

Glenview, Illinois, United States

Site Status

Kansas City, Kansas, United States

Site Status

New Orleans, Louisiana, United States

Site Status

Worcester, Massachusetts, United States

Site Status

Detroit, Michigan, United States

Site Status

Grand Rapids, Michigan, United States

Site Status

Minneapolis, Minnesota, United States

Site Status

Jackson, Mississippi, United States

Site Status

Lebanon, New Hampshire, United States

Site Status

Albuquerque, New Mexico, United States

Site Status

Albany, New York, United States

Site Status

Hawthorne, New York, United States

Site Status

Syracuse, New York, United States

Site Status

Charlotte, North Carolina, United States

Site Status

Cleveland, Ohio, United States

Site Status

Pittsburgh, Pennsylvania, United States

Site Status

Austin, Texas, United States

Site Status

Dallas, Texas, United States

Site Status

Fort Worth, Texas, United States

Site Status

Tyler, Texas, United States

Site Status

Charlottesville, Virginia, United States

Site Status

Richmond, Virginia, United States

Site Status

Madison, Wisconsin, United States

Site Status

Milwaukee, Wisconsin, United States

Site Status

Bron, , France

Site Status

Pierre-Bénite, , France

Site Status

Roscoff, , France

Site Status

Strasbourg, , France

Site Status

Dublin, , Ireland

Site Status

Birmingham, , United Kingdom

Site Status

Bristol, , United Kingdom

Site Status

London, , United Kingdom

Site Status

Manchester, , United Kingdom

Site Status

Southampton, , United Kingdom

Site Status

Countries

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United States France Ireland United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2015-004841-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VX15-371-101

Identifier Type: -

Identifier Source: org_study_id

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