Cystic FibrosisPhase 1SNO-1NCT01746784
Safety and Pharmacokinetic Study of N6022 in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation
A Phase 1 study testing N6022 and Normal saline in people with Cystic Fibrosis, run by Nivalis Therapeutics, Inc. at 17 sites in United States.
Trial summary
The purpose of this study is to investigate the safety, tolerability and pharmacokinetics of N6022, and to obtain descriptive information on the effect of N6022 on biomarkers of CFTR function and inflammation in adult cystic fibrosis subjects who are homozygous for the F508del-CFTR mutation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- N6022 and Normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 17 sitesUnited States
- Study dates
- Feb 2014to May 2014
- Phase
- Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Homozygous for F508del-CFTR gene
- Sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis
- Body weight ≥ 40 kg
- FEV1 ≥ 40% predicted
- Oxygen saturation ≥ 90% breathing ambient air
- Hematology and clinical chemistry of blood and urine results with no clinically significant abnormalities that would interfere with the study assessments
- Negative pregnancy test for women of child bearing potential
- Sexually active subjects of child bearing potential willing to follow contraception requirements
Who cannot join
- Previous enrollment in another cohort for this study.
- Any acute infection, including acute upper or lower respiratory infections and pulmonary exacerbations that require treatment within 4 weeks of Study Day 1.
- Any change in chronic therapies for CF lung disease within 4 weeks of Study Day 1.
- Blood hemoglobin <10 g/dL at screening.
- Serum albumin <2.5 g/dL at screening.
- Abnormal liver function defined as ≥ 3 x upper limit of normal (ULN) in three or more of the following: AST, ALT, GGT, ALP, total bilirubin at screening.
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- History of abnormal renal function (creatinine clearance < 50 mL/min using Cockcroft-Gault equation) within a year at screening.
- History, including the screening assessment, of ventricular tachycardia or other ventricular arrhythmias.
- History, including the screening assessment, of prolonged QT and/or QTcF interval (> 450 msec).
- History of solid organ or hematological transplantation.
- Intranasal medication changes within 14 days prior to Study Day 1
- Required Use of continuous (24 hr/d) or nocturnal supplemental oxygen.
- Concomitant use of any inhibitors or inducers of CYP3A4.
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
Providence Alaska Medical Center
Anchorage, Alaska, 99508
Children's Hospital Colorado
Aurora, Colorado, 80045
Johns Hopkins Hospital
Baltimore, Maryland, 21287
University of Alabama
Birmingham, Alabama, 35294
Boston Children's Hospital
Boston, Massachusetts, 02115
University of North Carolina
Chapel Hill, North Carolina, 27599
Northwestern University
Chicago, Illinois, 60611
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
Rainbow Babies and Children's Hospital - Case Medical Center
Cleveland, Ohio, 44106
Nationwide Children's Hospital
Columbus, Ohio, 43205
National Jewish Health
Denver, Colorado, 80206
University of Iowa Children's Hospital
Iowa City, Iowa, 52242
University of Minnesota
Minneapolis, Minnesota, 55455
Stanford University
Palo Alto, California, 94304
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Washington University
St Louis, Missouri, 63110
About this study
Official title: A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study of N6022 to Evaluate Safety and Pharmacokinetics in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation (SNO1)
The purpose of this study is to investigate the safety, tolerability and pharmacokinetics of N6022, and to obtain descriptive information on the effect of N6022 on biomarkers of CFTR function and inflammation in adult cystic fibrosis subjects who are homozygous for the F508del-CFTR mutation.
Read the detailed description
This is a double-blind, randomized, placebo-controlled, multicenter, sequential dose-escalation study which will occur in two parts. All selection criteria, assessments and procedures described in this protocol will be applied to both parts. Up to 5 cohorts will be studied with a total of 67 patients at approximately 18 clinical sites in the United States.
- Conditions
- Cystic Fibrosis
- Being tested
- N6022, Normal saline
- Keywords
- Cystic Fibrosis, F508del-CFTR, N6022, S-Nitrosoglutathione
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N6022Drug
Also called GSNORi
Intravenous solution of N6022 in normal saline administered by infusion pump over 1-8 minutes depending on the dose
Normal salineDrug
Also called Placebo
Intravenous solution of 0.9% (weight/volume) NaCl administered by infusion pump over 1-8 minutes depending on dose of active drug used in same cohort
| Study group | Role | What they receive |
|---|---|---|
| N6022 | Experimental | Subjects randomized to study drug will receive N6022 by intravenous infusion once per day for 7 days Receives: Drug: N6022 |
| Normal saline | Placebo comparator | Subjects randomized to placebo will receive normal saline administered intravenously using the same volume as the active drug group Receives: Drug: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability
Assessments are based on numbers of subjects with abnormal clinical evaluations, abnormal laboratory assessments, and adverse events.
Measured: Over 7 treatment days and 7 days of follow-up
Secondary outcomes (2)
Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson standards were used to calculate percent predicted FEV1 (for age, sex, and height).
Measured: Change from baseline at Day 7
Change in Biomarkers of CFTR Function
Sweat chloride millequivalents/Liter (mEq/L)
Measured: Change from baseline at Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2012 (estimated)
- Study startFeb 2014
- Primary completionApr 2014
- Study completionMay 2014
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.
- Publications (2)Papers the sponsor has linked to this study.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nivalis Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Scott Donaldson, MD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01746784
- Sponsor's protocol ID
- N6022-1CF1-04
- Acronym
- SNO-1
- Status last verified
- Nov 2014
- First submitted
- 6 Dec 2012
- Last updated
- 24 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.
PubMed 37983082Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
PubMed 33331662
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study of N6022 to Evaluate Safety and Pharmacokinetics in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation (SNO1)
- ClinicalTrials.gov ID
- NCT01746784
- Acronym / sponsor ID
- SNO-1 / N6022-1CF1-04
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic Fibrosis, F508del-CFTR, N6022, S-Nitrosoglutathione
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Nivalis Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Feb 2014
- Primary completion
- Apr 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 11 Dec 2012 (estimated)
- Results
- Posted 24 Nov 2014
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 investigate the safety, tolerability and pharmacokinetics of N6022, and to obtain descriptive information on the effect of N6022 on biomarkers of CFTR function and inflammation in adult cystic fibrosis subjects who are homozygous for the F508del-CFTR mutation.
Detailed description
This is a double-blind, randomized, placebo-controlled, multicenter, sequential dose-escalation study which will occur in two parts. All selection criteria, assessments and procedures described in this protocol will be applied to both parts. Up to 5 cohorts will be studied with a total of 67 patients at approximately 18 clinical sites in the United States.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| N6022 | Experimental | Drug: N6022Subjects randomized to study drug will receive N6022 by intravenous infusion once per day for 7 days |
| Normal saline | Placebo comparator | Drug: Normal salineSubjects randomized to placebo will receive normal saline administered intravenously using the same volume as the active drug group |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Homozygous for F508del-CFTR gene
- Sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis
- Body weight ≥ 40 kg
- FEV1 ≥ 40% predicted
- Oxygen saturation ≥ 90% breathing ambient air
Key exclusion criteria (13 listed)
- Previous enrollment in another cohort for this study.
- Any acute infection, including acute upper or lower respiratory infections and pulmonary exacerbations that require treatment within 4 weeks of Study Day 1.
- Any change in chronic therapies for CF lung disease within 4 weeks of Study Day 1.
- Blood hemoglobin <10 g/dL at screening.
- Serum albumin <2.5 g/dL at screening.
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 |
|---|---|---|
| N6022Also: GSNORiIntravenous solution of N6022 in normal saline administered by infusion pump over 1-8 minutes depending on the dose | Drug | N6022 |
| Normal salineAlso: PlaceboIntravenous solution of 0.9% (weight/volume) NaCl administered by infusion pump over 1-8 minutes depending on dose of active drug used in same cohort | Drug | Normal saline |
Primary outcome
Safety and Tolerability
Time frame: Over 7 treatment days and 7 days of follow-up
Assessments are based on numbers of subjects with abnormal clinical evaluations, abnormal laboratory assessments, and adverse events.
2 secondary outcomes
Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)
Time frame: Change from baseline at Day 7
Change in Biomarkers of CFTR Function
Time frame: Change from baseline at Day 7
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37983082Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.
- Derived from this study: PubMed 33331662Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
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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.
Scott Donaldson, MD principal investigator
University of North Carolina, Chapel Hill
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing N6022 and Normal saline in people with Cystic Fibrosis, run by Nivalis Therapeutics, Inc. at 17 sites in United States.
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 8 inclusion and 13 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 24 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States. 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. Some participants in this study may receive a placebo. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 24 Nov 2014). 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 (time frame: Over 7 treatment days and 7 days of follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01746784, which also lists 2 linked publications.
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 24 Nov 2014.