Summary

Eligibility
for people ages 18-80 (full criteria)
Location
at Sacramento, California and other locations
Dates
study started
estimated completion

Description

Summary

A randomized, double-blind, placebo-controlled dose escalation and verification study to assess the safety and efficacy of pulsed iNO versus placebo in subjects at risk for pulmonary hypertension associated with pulmonary fibrosis on long term oxygen therapy.

Official Title

A Randomized, Double-Blind, Placebo-Controlled Dose Escalation and Verification Clinical Study to Assess the Safety and Efficacy of Pulsed Inhaled Nitric Oxide (iNO) in Subjects at Risk of Pulmonary Hypertension Associated With Pulmonary Fibrosis on Long Term Oxygen Therapy (REBUILD)

Details

A phase 3, randomized, double-blind, placebo-controlled dose escalation clinical study to assess the safety and efficacy of pulsed inhaled nitric oxide (iNO) versus placebo in subjects with pulmonary fibrosis on long term oxygen therapy.

Keywords

Pulmonary Fibrosis Pulmonary Hypertension PF Inhaled Nitric Oxide iNO Long Term Oxygen Therapy Oxygen REBUILD Hypertension, Pulmonary Hypertension Fibrosis iNOpulse Open Label Extension Inhaled Nitric Oxide (iNO)

Eligibility

For people ages 18-80

Part 1: Blinded Treatment Period

Inclusion criteria: Subjects must meet all of the following inclusion criteria to be enrolled and eligible to participate in the study:

  1. Signed Informed Consent Form (and assent as appropriate) prior to the initiation of any study mandated procedures or assessments.
  2. Diagnosed with pulmonary fibrosis by high resolution CT scan performed in the 6 months prior to screening associated with one of the following conditions and confirmed using guidelines, as per American Thoracic Society (ATS) / European Respiratory Society (ERS) / Japanese Respiratory Society (JRS) / Latin American Thoracic Association (ALAT): Major IIPs (idiopathic interstitial pneumonias) diagnosis or suspected as one of the following:
  3. Idiopathic pulmonary fibrosis
  4. Idiopathic nonspecific interstitial pneumonia
  5. Respiratory bronchiolitis-interstitial lung disease
  6. Desquamative interstitial pneumonia
  7. Cryptogenic organizing pneumonia
  8. Acute interstitial pneumonia

Rare IIPs diagnosis by one of the following:

  • Idiopathic lymphoid interstitial pneumonia
  • Idiopathic pleuroparenchymal fibroelastosis

Unclassifiable idiopathic interstitial pneumonias

  • Chronic hypersensitivity pneumonitis
  • Occupational lung disease
  • Low or Intermediate/high probability of pulmonary hypertension (PH) by echocardiogram as assessed by local

Radiologist/Investigator, or PH as determined by a right heart catheterization (RHC) within 3 years prior to Baseline with the following parameters:

  1. Pulmonary vascular resistance (PVR) ≥ 3 Wood Units (WU) (320 dynes.sec.cm-5)
  2. A left ventricular end diastolic pressure (LVEDP) or pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg
  3. A mean pulmonary arterial pressure (mPAP) of ≥ 21 mmHg
  4. If a right heart catheterization is negative for PH within the past year, subjects will be stratified to low probability of PH
  5. Have been using oxygen therapy by nasal cannula for at least 4 weeks prior to the screening run-in period.
  6. 6MWD ≥ 100 meters and ≤ 400 meters at screening and Baseline/Randomization visits.
  7. World Health Organization (WHO) Functional Class II-IV
  8. Forced Vital Capacity ≥ 40% predicted within last 6 months prior to screening the screening run-in period.
  9. Willingness to use INOpulse delivery device for at least 12 hours per day
  10. Female subjects of childbearing potential must have a negative pre-treatment pregnancy test (serum or urine). All female subjects should take adequate precaution to avoid pregnancy.
  11. . Subjects must have completed at least 1 week of activity monitoring at time of the Baseline/Randomization visit.
  12. . During the Screening Run-In period prior to Baseline/Randomization, subjects must demonstrate the ability to consistently use the INOpulse device greater than 12 hrs/day in the opinion of the investigator.
  13. . Age between 18 and 80 years (inclusive)
  14. . Subject should be clinically stable for at least 4 weeks prior to Baseline/Randomization in the opinion of the Principal Investigator.
  15. . During the Screening Run-In period, subjects must demonstrate their ability to wear the activity monitor for at least 10 hours per day when awake at the time of the Baseline/Randomization visit in the opinion of the investigator.

Exclusion criteria: Subjects who meet any of the following criteria are not eligible for enrollment:

  1. Demonstrate symptomatic rebound defined as significant cardiopulmonary instability, such as systemic arterial oxygen desaturation, hypoxemia, bradycardia, tachycardia, systemic hypotension, shortness of breath, near-syncope, and syncope, occurring within 1 hour of acute iNO during rebound testing
  2. Episodes of disease worsening within 1 month prior to Baseline/Randomization
  3. Use of prostacyclin, guanylate cyclase stimulators, or endothelin receptor antagonists (ERA) pulmonary arterial hypertension (PAH)-specific medications regardless of reason for use (use of Phosphodiesterase-5 (PDE-5)) inhibitors regardless of reason for use is allowed)
  4. Acute or chronic physical impairment (other than dyspnea due to PF) that would limit the ability to comply with study procedures or adherence to therapy (i.e., 6MWT), including carrying and wearing the pulsed delivery INOpulse device per study protocol, or medical problem(s) likely to preclude completion of the study
  5. Pregnant or breastfeeding females at Screening
  6. Administered L-arginine within 1 month prior to Screening
  7. The concurrent use of the INOpulse device with a continuous positive airway pressure (CPAP), Bilevel positive airway pressure (BPAP), or any other positive pressure device.
  8. Use of investigational drugs or devices within 1 month prior to Screening (other than acute vasodilator testing with iNO)
  9. Any underlying medical or psychiatric condition that, in the opinion of the Investigator, makes the subject an unsuitable candidate for the study including unable to complete 6MWT
  10. . Any subject who has been enrolled in any previous clinical study with inhaled NO administered through pulse delivery
  11. . A definitive diagnosis of a connective tissue disease (eg, systemic sclerosis via American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria)
  12. . The presence of emphysema unless the extent of fibrotic changes is greater than the extent of emphysema on the most recent HRCT scan in the opinion of the local radiologist/Investigator.
  13. . A subject should not start a rehabilitation program during the study, not have started within 3 months of screening or change the nature of their rehabilitation program at any time during the blinded portion of the study.

Part 2: Open Label Period

Inclusion Criteria: Subjects must meet all of the following inclusion criteria to be eligible to participate in Part 2 of the trial:

  1. All subjects must have completed Part 1- Blinded Treatment Period study assessments.
  2. In the opinion of the investigator, the subject would benefit from continued therapy with iNO 45. For Cohort 1 and 2 subjects, if investigator believes the subject's prior treatment dose of iNO 30 or iNO 75 mcg/kg IBW/hr is medically justified and would benefit the subject, agreement with the Sponsor's Medical Monitor should be obtained prior to enrollment.

Exclusion Criteria:

  1. Use of prostacyclin, guanylate cyclase stimulator or ERA PAH-specific medications regardless of reason for use (use of PDE-5 inhibitors regardless of reason for use is allowed).
  2. The concurrent use of the INOpulse device with CPAP/BiPAP, or any other positive pressure device.

Locations

  • University of California Davis Health
    Sacramento California 95817 United States
  • David Geffen School of Medicine at UCLA
    Los Angeles California 90024 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Bellerophon Pulse Technologies
Links
Sign up for this study
ID
NCT03267108
Phase
Phase 2/3
Study Type
Interventional
Last Updated