Pulmonary Fibrosis, Pulmonary Hypertension
Conditions
Keywords
Pulmonary Fibrosis (PF), Pulmonary Hypertension, Inhaled Nitric Oxide, iNO, Long Term Oxygen Therapy, Oxygen
Brief summary
A randomized, double-blind, placebo-controlled dose escalation study to assess the safety and efficacy of pulsed, inhaled nitric oxide (iNO) in subjects with pulmonary fibrosis on long term oxygen therapy.
Detailed description
A Phase 2b, randomized, double-blind, placebo-controlled dose escalation clinical study to assess the safety and efficacy of pulsed, inhaled nitric oxide in subjects with and without pulmonary hypertension associated with pulmonary fibrosis on long term oxygen therapy (Part 1 and Part 2)
Interventions
COMBINATION_PRODUCTLong Term Follow Up
Patients will be treated by means of an INOpulse® device using an INOpulse® nasal cannula
COMBINATION_PRODUCTINOpulse®
Patients will be treated by means of an INOpulse® device using an INOpulse® nasal cannula
COMBINATION_PRODUCTPlacebo
Patients will be treated by means of an INOpulse® device using an INOpulse® nasal cannula
Sponsors
Bellerophon
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* 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 one of the following guidelines, as per American Thoracic Society (AGS) / European Respiratory Society (ERS) / Japanese Respiratory Society (JRS) / Latin American Thoracic Association (ALAT): * Major idiopathic interstitial pneumonias (IIPs) 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 * Have been using oxygen therapy by nasal cannula for at least 4 weeks * 6-Minute Walk Distance (6MWD) ≥ 100 meters and ≤ 450 meters at screening and Baseline/Randomization visits * World Health Organization (WHO) Functional Class II-IV * Forced Vital Capacity ≥ 40% predicated within the last 6 months prior to the screening run-in period * Age between 18 and 85 years (inclusive)
Exclusion criteria
* Pregnant or breastfeeding females at Screening * In the last 6 months prior to screening, evidence of any connective tissue disease with FVC \> 60% unless there is evidence of moderate to severe fibrosis on CT scan in the opinion of the local radiologist/Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of escalating doses of iNO in patient's life participation as assessed in minutes per day of moderate to vigorous activity. | Change from baseline to week 8 or 16 | Part 1 - Blinded Treatment Period |
Other
| Measure | Time frame | Description |
|---|---|---|
| Difference in activity as measured using ActiGraph devices | Change from baseline to week 8 or 16 | Part 1 - Blinded Treatment Period |
| Percentage of patients with ≥15% decrease in activity | Change from baseline to to week 8 or 16 | Part 1 - Blinded Treatment Period |
| Difference in dyspnea as measured by University of California San Diego Shortness of Breath Questionnaire | Change from baseline to to week 8 or 16 | The University of California San Diego Shortness of Breath Questionnaire 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). |
| Difference in St. George Respiratory Questionnaire and sub-groups | Change from baseline to to week 8 or 16 | St. George Respiratory Questionnaire and sub-groups 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) |
| Percentage of patients with a clinically meaningful difference (reduction of at least 4 points) in the disease-specific quality of life measured using the disease specific St. George Respiratory Questionnaire (SGRQ) | Change from baseline to to week 8 or 16 | Part 1 - Blinded Treatment Period |
| Change in N-terminal (NT)-ProBNP (absolute and percentage) | Change from baseline to week 8 or 16 | Part 1 - Blinded Treatment Period |
| Time to clinical improvement | Baseline to week 8 or 16 | Part 1 - Blinded Treatment Period |
| Change in 6-minute walking test (6MWT) from baseline | Change from baseline to week 8 or 16 | Part 1 - Blinded Treatment Period |
| Incidence and severity of treatment emergent adverse events, including those related to INOpulse® device deficiency | Baseline to week 8 or 16 | Part 1 - Blinded Treatment Period |
| Adverse events that may be due to rebound associated with a temporal acute withdrawal of investigational study drug | Baseline to week 8 or 16 | Part 1 - Blinded Treatment Period |
| Change in diffusing capacity of the lungs for carbon monoxide (DLCO) | Baseline to week 8 or 16 | Part 1 - Blinded Treatment Period |
| Mortality | Baseline to week 8 or 16 | Part 1 - Blinded Treatment Period |
| Hospitalization (all cause and for cardiopulmonary or other cause) | Baseline to week 8 or 16 | Part 1 - Blinded Treatment Period |
| Change in Forced Expiratory Volume at 1 minute (FEV1) | Baseline to week 8 or 16 | Part 1 - Blinded Treatment Period |
| Change in Forced Vital Capacity (FVC) | Baseline to week 8 or 16 | Part 1 - Blinded Treatment Period |
| Time to clinical worsening | Baseline to week 8 or 16 | Part 1 - Blinded Treatment Period |
Countries
United States
Outcome results
None listed