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

NCT02709109 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: VX15-371-1012015-004841-13
• Study Type: interventional
• Target: 147
• Locations: 4 countries
• Sites: 40

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

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline (Day 1) up to 28 days post last administration of study drug (up to 112 days)

• 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.

  Study baseline, Day 28

Secondary Outcomes (2)

• Plasma Concentrations of VX-371

  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

• Urine Concentrations of VX-371

  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

Study Arms (4)

Sequence 1: VX-371 + Hypertonic Saline (HS), then HS

EXPERIMENTAL

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

Sequence 2: HS, then VX-371 + HS

EXPERIMENTAL

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

Sequence 3: VX-371 + Placebo, then Placebo

EXPERIMENTAL

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; Drug: VX-371

Sequence 4: Placebo, then VX-371 + Placebo

EXPERIMENTAL

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; Drug: VX-371

Interventions

VX-371 + HS DRUG

Sequence 1: VX-371 + Hypertonic Saline (HS), then HS; Sequence 2: HS, then VX-371 + HS

Hypertonic saline DRUG

Sequence 1: VX-371 + Hypertonic Saline (HS), then HS; Sequence 2: HS, then VX-371 + HS

Placebo DRUG

Sequence 3: VX-371 + Placebo, then Placebo; Sequence 4: Placebo, then VX-371 + Placebo

Orkambi DRUG

Also known as: lumacaftor/ivacaftor

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

VX-371 DRUG

Sequence 3: VX-371 + Placebo, then Placebo; Sequence 4: Placebo, then VX-371 + Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Parion Sciences: lead
• Vertex Pharmaceuticals Incorporated: collaborator

Study Sites (40)

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Little Rock, Arkansas, United States

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Oakland, California, United States

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Gainesville, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Chicago, Illinois, United States

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Glenview, Illinois, United States

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Kansas City, Kansas, United States

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New Orleans, Louisiana, United States

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Worcester, Massachusetts, United States

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Detroit, Michigan, United States

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Grand Rapids, Michigan, United States

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Minneapolis, Minnesota, United States

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Jackson, Mississippi, United States

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Lebanon, New Hampshire, United States

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Albuquerque, New Mexico, United States

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Albany, New York, United States

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Hawthorne, New York, United States

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Syracuse, New York, United States

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Charlotte, North Carolina, United States

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Cleveland, Ohio, United States

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Pittsburgh, Pennsylvania, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Tyler, Texas, United States

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Charlottesville, Virginia, United States

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Richmond, Virginia, United States

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Madison, Wisconsin, United States

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Milwaukee, Wisconsin, United States

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Bron, France

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Pierre-Bénite, France

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Roscoff, France

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Strasbourg, France

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Dublin, Ireland

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Birmingham, United Kingdom

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Bristol, United Kingdom

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London, United Kingdom

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Manchester, United Kingdom

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Southampton, United Kingdom

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MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Saline Solution, Hypertonic; lumacaftor, ivacaftor drug combination

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Hypertonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Alison Church
• Organization: Parion Sciences

achurch@parion.com

919-313-1183

Study Officials

• Alison Church, MD

  Parion Sciences

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2016
• First Posted: March 15, 2016
• Study Start: February 1, 2016
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2017
• Last Updated: July 29, 2021
• Results First Posted: July 29, 2021

Record last verified: 2021-07

Locations

IE (1); US (30); GB (5); FR (4)