Efficacy and Safety of Inhaled Nitric Oxide (NO) in Cystic Fibrosis (CF) Patients

NCT02498535 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: NO-CF-02E
• Study Type: interventional
• Target: 49
• Locations: 2 countries
• Sites: 7

Brief 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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• 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.

  15 Days

Secondary Outcomes (12)

• Mean absolute change in FEV1% from baseline to Day 15 in the NO group (within group test).

  15 days

• Mean change in prevalent recovered organisms' sputum CFU g (log 10) from baseline to Days 10, 15 and 36

  36 days

• Mean change in distance walked in the six-minute walk test from baseline to Days 15 and 36.

  36 days

• Mean absolute change in FEV1 % predicted from baseline to Days 10 and 36.

  36 days

• Mean change in FEV1 % predicted (relative) from baseline to Days 10, 15, and 36.

  36 days

Study Arms (2)

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.

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).

Drug: Nitric Oxide 160 ppm

Interventions

Nitric Oxide 160 ppm DRUG

Nitric Oxide 160 ppm

Breathing 20.3% oxygen; Nitric oxide gas at 160 ppm

Eligibility Criteria

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

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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
• 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:

Sponsors & Collaborators

• Novoteris, LLC: lead
• Cystic Fibrosis Foundation: collaborator
• Mallinckrodt: collaborator

Study Sites (7)

* 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, United States

Location

Children's Hospital of Los Angeles (Adults can be treated here) (Site No. 500)

Los Angeles, California, 90027, United States

Location

Nationwide Children's Hospital (Adults can be treated here) (Site No. 600)

Columbus, Ohio, 43205, United States

Location

Medical University of South Carolina (Site No. 200)

Charleston, South Carolina, 29403, United States

Location

University of Washington Medical Center (Site No. 100)

Seattle, Washington, 98195, United States

Location

Medical College of Wisconsin (Site No. 400)

Milwaukee, Wisconsin, 53226, United States

Location

University of British Columbia, St. Paul's Hospital (Site No. 300)

Vancouver, B.C., V6Z 1Y6, Canada

Location

MeSH Terms

Conditions

Cystic Fibrosis

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

Study Design

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

Study Record Dates

• First Submitted: July 12, 2015
• First Posted: July 15, 2015
• Study Start: February 22, 2017
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: March 5, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); CA (1)