Cystic FibrosisPhase 2NCT02709109
A Study to Evaluate the Safety and Efficacy of VX-371 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation
A Phase 2 study testing VX-371 + HS, Hypertonic saline and Orkambi in people with Cystic Fibrosis, run by Parion Sciences at 40 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- VX-371 + HS, Hypertonic saline and Orkambi
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 147 participants
- Where
- 40 sitesin 4 countries
- Study dates
- Feb 2016to Sep 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
40 sites in 4 countries.
40 sites in 4 countries
United States30 sites
Study site
Albany, New York
Study site
Albuquerque, New Mexico
Study site
Austin, Texas
Study site
Charlotte, North Carolina
Study site
Charlottesville, Virginia
Study site
Chicago, Illinois
Study site
Cleveland, Ohio
Study site
Dallas, Texas
Study site
Detroit, Michigan
Study site
Fort Worth, Texas
Study site
Gainesville, Florida
Study site
Glenview, Illinois
Study site
Grand Rapids, Michigan
Study site
Hawthorne, New York
Study site
Jackson, Mississippi
Study site
Kansas City, Kansas
Study site
Lebanon, New Hampshire
Study site
Little Rock, Arkansas
Study site
Madison, Wisconsin
Study site
Miami, Florida
Study site
Milwaukee, Wisconsin
Study site
Minneapolis, Minnesota
Study site
New Orleans, Louisiana
Study site
Oakland, California
Study site
Orlando, Florida
Study site
Pittsburgh, Pennsylvania
Study site
Richmond, Virginia
Study site
Syracuse, New York
Study site
Tyler, Texas
Study site
Worcester, Massachusetts
United Kingdom5 sites
Study site
Birmingham
Study site
Bristol
Study site
London
Study site
Manchester
Study site
Southampton
France4 sites
Study site
Bron
Study site
Pierre-Bénite
Study site
Roscoff
Study site
Strasbourg
About this study
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
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
- Being tested
- VX-371 + HS, Hypertonic saline, Placebo, Orkambi, VX-371
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VX-371 + HSDrug
Hypertonic salineDrug
PlaceboDrug
OrkambiDrug
Also called lumacaftor/ivacaftor
VX-371Drug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Placebo; Drug: Orkambi; Drug: VX-371 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Study baseline, Day 28
Secondary outcomes (2)
Plasma Concentrations of VX-371
Measured: 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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2016 (estimated)
- Study startFeb 2016
- Primary completionSep 2017
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 147 participants (actual)
Sponsor and investigators
- Lead sponsor
- Parion Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Vertex Pharmaceuticals Incorporated
- Responsible party
- Sponsor
- Investigators
- Alison Church, MD, Study chair, Parion Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02709109
- Sponsor's protocol ID
- VX15-371-101
- Other IDs
- 2015-004841-13, 2015
- Status last verified
- Jul 2021
- First submitted
- 29 Feb 2016
- Last updated
- 29 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02709109
- Acronym / sponsor ID
- VX15-371-101
- Conditions
- Cystic Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 147 participants (actual)
- Lead sponsor
- Parion SciencesIndustry (pharma, biotech, devices)
- Collaborators
- Vertex Pharmaceuticals Incorporated
- Study start
- Feb 2016
- Primary completion
- Sep 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 15 Mar 2016 (estimated)
- Results
- Posted 29 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Sequence 1: VX-371 + Hypertonic Saline (HS), then HS | Experimental | Drug: VX-371 + HS, Drug: Hypertonic saline, Drug: OrkambiParticipants 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. |
| Sequence 2: HS, then VX-371 + HS | Experimental | Drug: VX-371 + HS, Drug: Hypertonic saline, Drug: OrkambiParticipants 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. |
| Sequence 3: VX-371 + Placebo, then Placebo | Experimental | Drug: Placebo, Drug: Orkambi, Drug: VX-371Participants 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. |
| Sequence 4: Placebo, then VX-371 + Placebo | Experimental | Drug: Placebo, Drug: Orkambi, Drug: VX-371Participants 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. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 |
| OrkambiAlso: lumacaftor/ivacaftor | Drug | 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 |
Primary outcome
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.
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.
2 secondary outcomes
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alison Church, MD study chair
Parion Sciences
40 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VX-371 + HS, Hypertonic saline and Orkambi in people with Cystic Fibrosis, run by Parion Sciences at 40 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in United States, United Kingdom, France, Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2021.