Cystic FibrosisPhase 2NCT02498535
Efficacy and Safety of Inhaled Nitric Oxide (NO) in Cystic Fibrosis (CF) Patients
A Phase 2 study testing Nitric Oxide 160 ppm in people with Cystic Fibrosis, run by Novoteris, LLC at 7 sites in 2 countries.
Trial summary
Prospective, randomized, placebo controlled, phase II clinical study of subjects crossing over from an approved inhaled antibiotic to inhaled nitric oxide as compared to a placebo control arm. 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?
- Nitric Oxide 160 ppm
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 22 Feb 2017to 1 Jun 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Confirmed diagnosis of Cystic Fibrosis based on the following criteria:
- positive sweat chloride 60 mEq/liter (by pilocarpine iontophoresis); and/or
- a genotype with two identifiable mutations consistent with CF
- Presence of Pseudomonas aeruginosa, Staphylococcus aureus or Stenotrophomonas maltophilia in the screening sputum culture.
- Chronic microbial lung colonization (≥6 months) with presence of Pseudomonas aeruginosa, Staphylococcus aureus or Stenotrophomonas maltophilia in at least two (2) sputum cultures in the past year (the screening culture can count as one of the two positive cultures).
- Ongoing chronic inhaled antibiotic therapy for at least 3 months prior to (screening or baseline).
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- For subjects on cycled therapy, at least 2 cycles of drug need to have been completed prior to baseline.
- Willing to be off of inhaled antibiotic therapy from Day 1 to Day 15
- Male or female subjects ≥18 years
- FEV1 <85% and >35% at screening and baseline
- SaO2 >90% on room air at screening and baseline
- Clinically stable with no significant changes in health status within 14 days prior to Baseline
- Written Informed Consent and HIPAA authorization
- Non-smoker for at least 6 months prior to screening and agrees not to smoke during the study
- Chest x-ray within the last six (6) months. If none, a chest x-ray is required before randomization.
- Willing and able to comply with the treatment schedule and procedures.
Who cannot join
- Initiation of any new chronic therapy (e.g., ibuprofen, Pulmozyme®, hypertonic saline, azithromycin, TOBI®, Cayston®) within 4 weeks prior to screening.
- Use of antibiotics [oral, intravenous (iv), and/or inhaled] for acute respiratory symptoms within 2 weeks prior to baseline.
- Significant hemoptysis within 30 days prior to screening (≥5 mL of blood in one coughing episode or >30 mL of blood in a 24 hour period)
- History of colonization with nontuberculosis mycobacterium in sputum culture. The investigator can be guided by the following suggested criteria for a subject to be considered free of colonization:
- Two respiratory tract cultures negative for NTM in the last year, with no subsequent positive cultures; and
- these 2 respiratory cultures must be separated by at least 3 months; and
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- one of these two cultures has to have been obtained within the last 6 months
- Cardiac (left heart) insufficiency (defined as LVEF <35%) at screening
- Use of a nitric oxide donor agent such as nitroglycerin or drugs known to increase methemoglobin such as lidocaine, prilocaine, benzocaine or dapsone at screening
- Any of the following abnormal lab values at Screening:
- Hemoglobin < 10 g/dl
- Methemoglobn >3%
- Platelet count <100,000/mm3
- Prothrombin time international ratio (INR) > 1.5
- Abnormal liver function defined as any two of the following:
- ALT >3 x ULN
- AST >3 x ULN
- ALP > 3 x ULN
- GGT > 3 x ULN
- Abnormal liver function defined as:
- ALT >5 x ULN
- AST >5 x ULN
- Abnormal renal function defined as:
- Calculated Creatinine Clearance < 50 mL (as calculated by Cockcroft/Gault)
- For women of child bearing potential:
- positive pregnancy test at screening or
- lactating or
- unwilling to practice a medically acceptable form of contraception from screening to Day 36 (acceptable forms of contraception: abstinence, hormonal birth control, intrauterine device, or barrier method plus a spermicidal agent)
- Use of an investigational drug within 30 days prior to screening
- Intravenous or oral steroids in the 14 days prior to screening
- Current use of inhaled steroids >500 micrograms twice daily of Fluticasone or equivalent in the 30 days prior to screening
- Use of supplemental oxygen (daytime or nocturnal) in the 7 days prior to screening
- Any condition that the Investigator believes would interfere with the intent of this study or would make participation not in the best interest of the subject
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States6 sites
Medical University of South Carolina (Site No. 200)
Charleston, South Carolina, 29403
Nationwide Children's Hospital (Adults can be treated here) (Site No. 600)
Columbus, Ohio, 43205
* Entire USA* The sponsor will provide air transportation and housing to patients that are not located in the area of clinical trial sites. All trial sites can treat adults.
Garden Grove, California, 92841
Children's Hospital of Los Angeles (Adults can be treated here) (Site No. 500)
Los Angeles, California, 90027
Medical College of Wisconsin (Site No. 400)
Milwaukee, Wisconsin, 53226
University of Washington Medical Center (Site No. 100)
Seattle, Washington, 98195
Canada1 site
University of British Columbia, St. Paul's Hospital (Site No. 300)
Vancouver, B.C., V6Z 1Y6
About this study
Official title: Prospective, Randomized, Placebo Controlled Trial of the Efficacy and Safety of Inhaled Nitric Oxide (NO) in Cystic Fibrosis (CF) Patients
Prospective, randomized, placebo controlled, phase II clinical study of subjects crossing over from an approved inhaled antibiotic to inhaled nitric oxide as compared to a placebo control arm.
Read the detailed description
This is a multi-center, randomized, placebo controlled, phase II clinical study comparing an investigational drug to a placebo control. Screening data will be reviewed to determine subject eligibility. All subjects including screen failure subjects will be recorded on screening logs at their respective sites. Upon successful completion of all screening procedures, a subject will be considered eligible for enrollment. The subject will be enrolled and randomized in as close a time proximity to the first treatment application as is possible in order to minimize the possibility of dropout while enrolled but before undergoing treatment. With a 1:1 investigational treatment to placebo control, subjects will be randomized to one of the two arms. Subjects in the investigational treatment arm will be administered doses of NO (0.5% NO in 99.5% nitrogen) diluted in room air by inhalation four times daily (30-minute inhalations at least 3 hours apart) for 7.5 days on Days 1, 2, 3, 4, 5, 8, 9, and 10 (three treatments on Days 1 and 10). Subjects in the placebo arm will breathe 100% nitrogen diluted in room air in the same proportion as the investigational arm. Subjects will remain in the clinic for 30 minutes after completing the last treatment of each day. All subjects will be asked to return to the clinic for additional evaluations on Days 15 and 36.
- Conditions
- Cystic Fibrosis
- Being tested
- Nitric Oxide 160 ppm
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric Oxide 160 ppmDrug
Nitric Oxide 160 ppm
| Study group | Role | What they receive |
|---|---|---|
| Nitric oxide gas at 160 ppm | Experimental | Nitric oxide gas at 160 ppm inhaled four times daily for 30 min delivered with air as the carrier via nasal inhalation for a total of 7.5 days. Total dose of 2400 ppm hours. Receives: Drug: Nitric Oxide 160 ppm |
| Breathing 20.3% oxygen | Placebo comparator | Breathing 20.3% oxygen inhaled four times daily for 30 min delivered with air as the carrier via nasal inhalation for a total of 7.5 days.. 100% nitrogen will be injected into the breathing circuit (instead of 99.5% nitrogen and 0.5% NO). Receives: Drug: Nitric Oxide 160 ppm |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in FEV1 % predicted from baseline to Day 15
The primary efficacy variable for this study is absolute change from baseline FEV1% predicted to Day 15. For each subject, the change will be calculated as the FEV1% value minus the baseline FEV1%, i.e., a positive change in FEV1% values will indicate an increase in FEV1% after treatment. The primary endpoint for this trial is the comparison of the mean absolute change from baseline in FEV1% between treatment groups.
Measured: 15 Days
Secondary outcomes (12)
Mean absolute change in FEV1% from baseline to Day 15 in the NO group (within group test).
Clinical Measurement of Mean absolute change in FEV1% from baseline to Day 15 in the NO group (within group test).
Measured: 15 days
Mean change in prevalent recovered organisms' sputum CFU g (log 10) from baseline to Days 10, 15 and 36
Clinical Measurement of Mean change in prevalent recovered organisms' sputum CFU g (log 10) from baseline to Days 10, 15 and 36
Measured: 36 days
Mean change in distance walked in the six-minute walk test from baseline to Days 15 and 36.
Clinical Measurement of Mean change in distance walked in the six-minute walk test from baseline to Days 15 and 36.
Measured: 36 days
Mean absolute change in FEV1 % predicted from baseline to Days 10 and 36.
Clinical Measurement of Mean absolute change in FEV1 % predicted from baseline to Days 10 and 36.
Measured: 36 days
Mean change in FEV1 % predicted (relative) from baseline to Days 10, 15, and 36.
Clinical Measurement of Mean change in FEV1 % predicted (relative) from baseline to Days 10, 15, and 36.
Measured: 36 days
Mean change in FVC from baseline to Days 10, 15 and 36
Clinical Measurement of Mean change in FVC from baseline to Days 10, 15 and 36
Measured: 36 days
Mean change in FEF25-75 from baseline to Days 10, 15 and 36
Clinical Measurement of Mean change in FEF25-75 from baseline to Days 10, 15 and 36
Measured: 36 days
Mean change in CFQ-R scores for each domain from baseline to Days 15 and 36
Clinical Measurement of Mean change in CFQ-R scores for each domain from baseline to Days 15 and 36
Measured: 36 days
Counts of CFRSD-CRISS symptom scores for each symptom from evening prior to Day 1 to each day of the study (Days 1-35)
Clinical Measurement of Counts of CFRSD-CRISS symptom scores for each symptom from evening prior to Day 1 to each day of the study (Days 1-35)
Measured: 35 days
Number of subjects with a relative improvement between baseline and Day 10 in FEV1 % predicted of ≥7.5%
Clinical Measurement of Number of subjects with a relative improvement between baseline and Day 10 in FEV1 % predicted of ≥7.5%
Measured: 10 days
Number of subjects with an absolute improvement in CFQ-R survey scores ≥5 between baseline and Days 15 and 36
Clinical Measurement of Number of subjects with an absolute improvement in CFQ-R survey scores ≥5 between baseline and Days 15 and 36
Measured: 36 days
Number of subjects with a positive response in the 6 minute walk test at Days 15 and 36
Clinical Measurement of Number of subjects with a positive response in the 6 minute walk test at Days 15 and 36
Measured: 36 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2015 (estimated)
- Study start22 Feb 2017
- Primary completion1 Jun 2020
- Study completion1 Jun 2020
Why it stopped: Terminated for the safety of cystic fibrosis clinical trial subjects due to Covid-19.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novoteris, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cystic Fibrosis Foundation, Mallinckrodt
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02498535
- Sponsor's protocol ID
- NO-CF-02E
- Status last verified
- Mar 2021
- First submitted
- 12 Jul 2015
- Last updated
- 5 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Randomized, Placebo Controlled Trial of the Efficacy and Safety of Inhaled Nitric Oxide (NO) in Cystic Fibrosis (CF) Patients
- ClinicalTrials.gov ID
- NCT02498535
- Acronym / sponsor ID
- NO-CF-02E
- Conditions
- Cystic Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated for the safety of cystic fibrosis clinical trial subjects due to Covid-19.
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Novoteris, LLCIndustry (pharma, biotech, devices)
- Collaborators
- Cystic Fibrosis Foundation, Mallinckrodt
- Study start
- 22 Feb 2017 (actual)
- Primary completion
- 1 Jun 2020 (actual)
- Study completion
- 1 Jun 2020 (actual)
- First posted
- 15 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prospective, randomized, placebo controlled, phase II clinical study of subjects crossing over from an approved inhaled antibiotic to inhaled nitric oxide as compared to a placebo control arm.
Detailed description
This is a multi-center, randomized, placebo controlled, phase II clinical study comparing an investigational drug to a placebo control. Screening data will be reviewed to determine subject eligibility. All subjects including screen failure subjects will be recorded on screening logs at their respective sites. Upon successful completion of all screening procedures, a subject will be considered eligible for enrollment. The subject will be enrolled and randomized in as close a time proximity to the first treatment application as is possible in order to minimize the possibility of dropout while enrolled but before undergoing treatment. With a 1:1 investigational treatment to placebo control, subjects will be randomized to one of the two arms. Subjects in the investigational treatment arm will be administered doses of NO (0.5% NO in 99.5% nitrogen) diluted in room air by inhalation four times daily (30-minute inhalations at least 3 hours apart) for 7.5 days on Days 1, 2, 3, 4, 5, 8, 9, and 10 (three treatments on Days 1 and 10). Subjects in the placebo arm will breathe 100% nitrogen diluted in room air in the same proportion as the investigational arm. Subjects will remain in the clinic for 30 minutes after completing the last treatment of each day. All subjects will be asked to return to the clinic for additional evaluations on Days 15 and 36.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nitric oxide gas at 160 ppm | Experimental | Drug: Nitric Oxide 160 ppmNitric oxide gas at 160 ppm inhaled four times daily for 30 min delivered with air as the carrier via nasal inhalation for a total of 7.5 days. Total dose of 2400 ppm hours. |
| Breathing 20.3% oxygen | Placebo comparator | Drug: Nitric Oxide 160 ppmBreathing 20.3% oxygen inhaled four times daily for 30 min delivered with air as the carrier via nasal inhalation for a total of 7.5 days.. 100% nitrogen will be injected into the breathing circuit (instead of 99.5% nitrogen and 0.5% NO). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Confirmed diagnosis of Cystic Fibrosis based on the following criteria:
- Presence of Pseudomonas aeruginosa, Staphylococcus aureus or Stenotrophomonas maltophilia in the screening sputum culture.
- Chronic microbial lung colonization (≥6 months) with presence of Pseudomonas aeruginosa, Staphylococcus aureus or Stenotrophomonas maltophilia in at least two (2) sputum cultures in the past year (the screening culture can count as one of the two positive cultures).
- Ongoing chronic inhaled antibiotic therapy for at least 3 months prior to (screening or baseline).
- Willing to be off of inhaled antibiotic therapy from Day 1 to Day 15
Key exclusion criteria (33 listed)
- Initiation of any new chronic therapy (e.g., ibuprofen, Pulmozyme®, hypertonic saline, azithromycin, TOBI®, Cayston®) within 4 weeks prior to screening.
- Use of antibiotics [oral, intravenous (iv), and/or inhaled] for acute respiratory symptoms within 2 weeks prior to baseline.
- Significant hemoptysis within 30 days prior to screening (≥5 mL of blood in one coughing episode or >30 mL of blood in a 24 hour period)
- History of colonization with nontuberculosis mycobacterium in sputum culture. The investigator can be guided by the following suggested criteria for a subject to be considered free of colonization:
- Cardiac (left heart) insufficiency (defined as LVEF <35%) 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 |
|---|---|---|
| Nitric Oxide 160 ppmNitric Oxide 160 ppm | Drug | Breathing 20.3% oxygen, Nitric oxide gas at 160 ppm |
Primary outcome
Change in FEV1 % predicted from baseline to Day 15
Time frame: 15 Days
The primary efficacy variable for this study is absolute change from baseline FEV1% predicted to Day 15. For each subject, the change will be calculated as the FEV1% value minus the baseline FEV1%, i.e., a positive change in FEV1% values will indicate an increase in FEV1% after treatment. The primary endpoint for this trial is the comparison of the mean absolute change from baseline in FEV1% between treatment groups.
12 secondary outcomes
Mean absolute change in FEV1% from baseline to Day 15 in the NO group (within group test).
Time frame: 15 days
Mean change in prevalent recovered organisms' sputum CFU g (log 10) from baseline to Days 10, 15 and 36
Time frame: 36 days
Mean change in distance walked in the six-minute walk test from baseline to Days 15 and 36.
Time frame: 36 days
Mean absolute change in FEV1 % predicted from baseline to Days 10 and 36.
Time frame: 36 days
Mean change in FEV1 % predicted (relative) from baseline to Days 10, 15, and 36.
Time frame: 36 days
Mean change in FVC from baseline to Days 10, 15 and 36
Time frame: 36 days
Mean change in FEF25-75 from baseline to Days 10, 15 and 36
Time frame: 36 days
Mean change in CFQ-R scores for each domain from baseline to Days 15 and 36
Time frame: 36 days
Counts of CFRSD-CRISS symptom scores for each symptom from evening prior to Day 1 to each day of the study (Days 1-35)
Time frame: 35 days
Number of subjects with a relative improvement between baseline and Day 10 in FEV1 % predicted of ≥7.5%
Time frame: 10 days
Number of subjects with an absolute improvement in CFQ-R survey scores ≥5 between baseline and Days 15 and 36
Time frame: 36 days
Number of subjects with a positive response in the 6 minute walk test at Days 15 and 36
Time frame: 36 days
Results and safety
The study was stopped early (reason given: Terminated for the safety of cystic fibrosis clinical trial subjects due to Covid-19.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2021.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nitric Oxide 160 ppm in people with Cystic Fibrosis, run by Novoteris, LLC at 7 sites in 2 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 16 inclusion and 33 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: stopped early, as of the sponsor's last update on 5 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Canada. 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 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?
The study was stopped early (reason given: Terminated for the safety of cystic fibrosis clinical trial subjects due to Covid-19.). Results are not available in the source record.
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?
Change in FEV1 % predicted from baseline to Day 15 (time frame: 15 Days). 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 5 Mar 2021.