A Study to Assess Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis at Risk for Pulmonary Hypertension (REBUILD)

• ClinicalTrials.gov Identifier: NCT03267108
• Recruitment Status: Active, not recruiting
• First Posted: August 30, 2017
• Last Update Posted: February 21, 2023
• Sponsor: Bellerophon Pulse Technologies
• Information provided by (Responsible Party): Bellerophon ( Bellerophon Pulse Technologies )

Tracking Information

• First Submitted Date: August 27, 2017
• First Posted Date: August 30, 2017
• Last Update Posted Date: February 21, 2023
• Actual Study Start Date: December 14, 2020
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 5, 2020)

• Change in Moderate to Vigorous Physical Activity (MVPA) as Measured by Actigraphy [ Time Frame: Baseline to Month 4 ]
  Part 1 - Blinded Treatment Period
• Adverse Events and Serious Adverse Events with Long Term INOpulse Therapy [ Time Frame: Baseline to Month 4 ]
  Part 2 - Open Label Extension (OLE)

Original Primary Outcome Measures (submitted: August 27, 2017)

6 Minute Walk Distance (6MWD) [ Time Frame: 8 weeks ]

Change in 6MWD from baseline to Week 8

Current Secondary Outcome Measures (submitted: October 5, 2020)

• Change in Overall Activity as Measured by Actigraphy [ Time Frame: Baseline to M4 ]
  Part 1 - Blinded Treatment Period
• Change in University of California San Diego (UCSD) Shortness of Breath Questionnaire (SOBQ) [ Time Frame: Baseline to Month 4 ]
  Part 1 Blinded Treatment Period: The UCSD SOBQ is a 24-item questionnaire developed to measure breathlessness associated with activities of daily living, on a scale between zero and five where 0 is not at all breathless and 5 is maximally breathless or too breathless to do the activity. The responses to all items are summed up to provide the overall score that can range from 0 (best outcome) to 120 (worst outcome).
• Change in St. George Respiratory Questionnaire (SGRQ) - Activity, Impacts & Total [ Time Frame: Baseline to Month 4 ]
  Part 1 Blinded Treatment Period: SGRQ is a tool for assessing quality of life that has previously been validated for the use with patients with interstitial lung disease. It is a responsive tool that has three domains: symptoms, activity and impact (on daily life)
• Time to Clinical Worsening [ Time Frame: Baseline to Month 4 ]
  Part 1 - Blinded Treatment Period
• Time to Clinical Deterioration [ Time Frame: Baseline to Month 4 ]
  Part 1 Blinded Treatment Period
• Time to Clinical Improvement [ Time Frame: Baseline to Month 4 ]
  Part 1 Blinded Treatment Period
• Change in 6 Minute Walk Distance [ Time Frame: Baseline to Month 4 ]
  Part 1 Blinded Treatment Period

Original Secondary Outcome Measures (submitted: August 27, 2017)

Right Ventricular Function (RVF) [ Time Frame: 8 weeks ]

Change in RVF as measured by RV Tei index and RV free wall longitudinal strain from baseline to Week 8

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: August 27, 2017)

• Nadir SpO2 [ Time Frame: 8 weeks ]
  Difference in Nadir SpO2 during 6MWT from baseline to Week 8
• Oxygen desaturation [ Time Frame: 8 weeks ]
  Difference in oxygen desaturation during 6MWT from baseline to Week 8
• Distance Saturation Product (DSP) [ Time Frame: 8 weeks ]
  Difference in DSP from baseline to Week 8
• Integral Distance Saturation Product (IDSP) [ Time Frame: 8 weeks ]
  Difference in IDSP from baseline to Week 8
• Activity [ Time Frame: 8 weeks ]
  Difference in Activity as measured by activity monitoring from baseline to Week 8
• Dyspnea [ Time Frame: 8 weeks ]
  Difference in Dyspnea as measured by UCSD Shortness of Breath (SOB) questionnaire from baseline to Week 8
• Quality of Life [ Time Frame: 8 weeks ]
  Difference in disease-specific Quality of Life as measured by St. George Respiratory questionnaire (SGRQ) from baseline to Week 8

Descriptive Information

• Brief Title: A Study to Assess Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis at Risk for Pulmonary Hypertension
• 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 (Part 1 and Part 2) - REBUILD
• Brief Summary: A randomized, double-blind, placebo-controlled dose escalation and verification study to assess the safety and efficacy of pulsed inhaled nitric oxide (iNO) in subjects at risk for pulmonary hypertension associated with pulmonary fibrosis on long term oxygen therapy (Part 1 and Part 2) - REBUILD
• Detailed Description: This is a Phase 3, 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 for pulmonary hypertension associated with pulmonary fibrosis on long term oxygen therapy (Part 1 and Part 2) - REBUILD
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Pulmonary Fibrosis
• Pulmonary Hypertension

Intervention

• Combination Product: INOpulse®
  Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.
• Combination Product: Placebo
  Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.
• Combination Product: Open Label Extension
  Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.

Study Arms

• Active Comparator: Inhaled Nitric Oxide (iNO)
  Pulsed inhaled iNO 45 mcg/kg Ideal Body Weight (IBW)/hour (hr)
  Intervention: Combination Product: INOpulse®
• Placebo Comparator: Placebo
  Pulsed inhaled N2, 99.999% gas
  Intervention: Combination Product: Placebo
• Open Label Extension
  Pulsed inhaled iNO 45 mcg/kg IBW/hr
  Intervention: Combination Product: Open Label Extension

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 19, 2023): 145
• Original Estimated Enrollment (submitted: August 27, 2017): 40
• Estimated Study Completion Date: September 2024
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria:

• A 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:

    • Idiopathic pulmonary fibrosis
    • Idiopathic nonspecific interstitial pneumonia
    • Respiratory bronchiolitis-interstitial lung disease
    • Desquamative interstitial pneumonia
    • Cryptogenic organizing pneumonia
    • 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
  • Connective Tissue Disease associated with IPF (CTD-ILD)
  • Interstitial Pneumonia with Autoimmune Features (IPAF)
• Have been using oxygen therapy by nasal cannula for at least 4 weeks (including use limited to exertion)
• 6MWD ≥ 100 meters and ≤ 400 meters at screening and Baseline/Randomization visits.
• World Health Organization (WHO) Functional Class II-IV
• Forced Vital Capacity ≥ 40% predicted within the 60 day Screening period
• Age between 18 and 80 years (inclusive) at screening

Exclusion criteria:

• For women of child-bearing potential: Pregnant or breastfeeding females at Screening, or planning to get pregnant, or unwilling to use appropriate contraception if sexually active to avoid pregnancy during the study and for at least 30 days after discontinuation of the study drug.
• Heart failure with reduced ejection fraction (HFrEF; systolic heart failure) with an ejection fraction of < 40%; or severe HF with preserved EF (HFpEF; diastolic HF)
• History of sarcoidosis
• History of chronic thrombo-embolic pulmonary hypertension (CTEPH; WHO group 4 PH)
• Smoking within 3 months of Screening and/or unwilling to avoid smoking throughout the study
• Body mass index (BMI) >40 kg/m2 at screening
• Intermittent uncontrolled atrial fibrillation, in the opinion of the Principal Investigator
• Known severe hepatic impairment, in the opinion of the Principal Investigator
• Known severe renal impairment (Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) 2009 equation [Levy 2009] calculated creatinine clearance <30 ml/min) at screening

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT03267108
• Other Study ID Numbers: PULSE-PHPF-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Bellerophon ( Bellerophon Pulse Technologies )
• Original Responsible Party: Same as current
• Current Study Sponsor: Bellerophon Pulse Technologies
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Ashika Ahmed; Bellerophon Therapeutics

• PRS Account: Bellerophon
• Verification Date: January 2023