Study in Subjects With PAH and PH Secondary to IPF Using Inhaled GeNOsyl.

NCT01265888 | Completed Phase 2

• 2 other identifiers: Protocol # GeNO-P-2010-002PHiano
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 10

Brief Summary

A Phase 2 open label, dose escalation study to find the minimally and maximum effective dose (dose beyond which no further effect on PVR is seen) of inhaled nitric oxide generated by the GeNOsyl® System compared to placebo.

Conditions

Pulmonary Arterial Hypertension; Idiopathic Pulmonary Fibrosis

Keywords

PAH; PH IPF

Outcome Measures

Primary Outcomes (1)

• Identify the minimally and maximum effective doses of inhaled nitric oxide generated by the GeNOsyl® System compared to placebo.

  Assess mean change in pulmonary vascular resistance (PVR) for study drug dose 2 compared to placebo. Assess change from pre-dose to end-of-hemodynamic assessment for study drug dose 1. Assess change from placebo to end-of-hemodynamic assessment for study drug dose 2.

  through end of Right Heart Catheterization procedure (Treatment Phase approximately 3 hours)

Secondary Outcomes (2)

• Assess the safety and tolerability of nitric oxide generated by the GeNOsyl® System in subjects with WHO Group 1 PAH and WHO Group 3 PH-IPF.

  through end of study (approximately 30 days after treatment visit)

• Evaluate the pharmacokinetics of total nitrates/nitrites and methemoglobin produced following inhalation of nitric oxide via the GeNOsyl® System.

  up through 24 hrs after treatment period for subjects participating in PK sub-study

Study Arms (3)

Dosing Group 1

EXPERIMENTAL

1 Liter per Minute (LPM)of inhaled nitric oxide via nasal cannula: approximately 5 parts per million (ppm)

Drug: Inhaled Nitric Oxide

Dosing Group 2

EXPERIMENTAL

2 LPM of inhaled nitric oxide via nasal cannula: approximately 15 ppm

Drug: Inhaled Nitric Oxide

Dosing Group 3

EXPERIMENTAL

4 LPM of inhaled nitric oxide via nasal cannula: approximately 20 ppm

Drug: Inhaled Nitric Oxide

Interventions

Inhaled Nitric Oxide DRUG

Inhaled nitric oxide 80 ppm via nasal cannula at 1 LPM for 15 minutes followed by placebo washout of 15 minutes inhalation of medical grade air (or prescribed supplemental oxygen), and then inhaled nitric oxide 80 ppm via nasal cannula at 1 LPM

Also known as: GeNOsyl

Dosing Group 1

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PAH and PH-IPF
• WHO Functional Class (or equivalent classification) II - IV.
• Subjects using supplemental oxygen must be receiving a stable course of therapy for a minimum of 14 days prior to study drug administration.
• All subjects' oxygen saturation must be \> or = to 88% at time of treatment
• Echocardiogram within 6 months of baseline showing no signs of clinically significant left sided heart disease
• Females of child-bearing potential with a negative urine pregnancy test, or a documented surgical sterilization, or is post-menopausal prior to administration of investigational product. Females of childbearing potential must be practicing adequate birth control.
• Documented diagnosis of WHO Group 1 PAH, (limited to, idiopathic, heritable, drug and toxin induced, associated with connective tissue disease, portal hypertension, repaired congenital heart disease, HIV); documented by a previous RHC and hemodynamics consistent with PAH, WHO Group 1
• Pulmonary Function Testing within 6 months prior to screening/enrollment shows no evidence of interstitial lung disease (TLC\<70%) or obstructive lung disease (FEV1/FVC ratio \<50%)
• Receiving a stable course of approved PAH oral mono therapies for a minimum of 14 days prior to treatment period
• Must be 18-80 year of age
• Documented diagnosis of probable or definite IPF using ATS/ERS criteria
• Previous transbronchial biopsy, if performed, shows no features to support a definitive alternative diagnosis
• Previous bronchoalveolar lavage, if performed, shows no features that provides an alternative diagnosis
• FVC \> or = 40% within 6 months of baseline visit
• Diagnosis of PH based on hemodynamic requirements

You may not qualify if:

• PAH and PH-IPF
• Have any other disease associated with pulmonary hypertension (i.e. Group II, IV or V).
• Documented uncontrolled systemic hypertension.
• Left ventricular ejection fraction (LVEF) \< 40%.
• Have chronic kidney disease stage IV or worse, or requires dialysis.
• Be receiving an investigational drug, have in place an investigational device, or have participated in an investigational drug study within past 30 days.
• Have had an atrial septostomy.
• Have anemia or any other ongoing condition that would interfere with the interpretation of study assessments.
• Have any serious or life-threatening disease other than conditions associated with PAH or PH-IPF (e.g. malignancy requiring aggressive chemotherapy, renal dialysis, etc.)
• Significant, ongoing alcohol or drug abuse, or unstable psychiatric status.
• Receiving inhaled or parenteral prostacyclins or a non-approved combination of approved oral PAH therapy.
• Pregnant or lactating subjects
• Have had any changes to chronic therapy (including but not limited to oxygen, a different category of vasodilator, a diuretic, digoxin) for PAH added within 14 days of study drug administration. Anticoagulants are allowed to be discontinued per institutional standard of care.
• History of untreated sleep apnea within three months of study drug administration.
• History of hemodynamically significant left-sided heart disease or evidence of left-sided heart disease.

Sponsors & Collaborators

• Geno LLC: lead

Study Sites (10)

University of Alabama @ Birmingham

Birmingham, Alabama, 35294, United States

Location

VA Greater LA Health Care System-UCLA

Los Angeles, California, 90073, United States

Location

University of California- Davis Medical Center

Sacramento, California, 95817, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Kentuckiana Pulmonary Associates

Louisville, Kentucky, 40204, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Medicine and Dentistry of New Jersey

Newark, New Jersey, 07103, United States

Location

Ohio State University, Martha Morehouse Medical Plaza

Columbus, Ohio, 43221, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75239, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Idiopathic Pulmonary Fibrosis

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Pulmonary Fibrosis; Lung Diseases, Interstitial

Study Officials

• Gregory Suplick

  Geno LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2010
• First Posted: December 23, 2010
• Study Start: March 1, 2011
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: September 19, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will share

Locations

US (10)