Study of PAH Subjects With LTOT Use That Have Demonstrated Improved Exercise Tolerance With the Use of Inhaled Nitric

Phase 3, Multicenter, Randomized, Double-blind, Placebo Controlled Withdrawal Study of Pulmonary Arterial Hypertension(PAH) Subjects With LTOT Use That Have Demonstrated Improved Exercise Tolerance With the Use of Inhaled Nitric Oxide (INO)

Study of PAH Subjects with LTOT Use that have Demonstrated Improved Exercise Tolerance with the use of Inhaled Nitric Oxide

Study Overview

• Status: Withdrawn
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: iNO

Detailed Description

Phase 3, Multicenter, Randomized, Double-blind, Placebo Controlled Withdrawal Study of Pulmonary Arterial Hypertension(PAH) Subjects with LTOT Use that have Demonstrated Improved Exercise Tolerance with the use of Inhaled Nitric Oxide (INO)

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T1Y6J4
      • Peter Lougheed Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital, University Health Network
• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Bluhm Cardiovascular Institute, Clinical Trials Unit
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed Informed Consent Form prior to the initiation of any study mandated procedures or assessments
2. Subjects must be enrolled in the PULSE PAH-004 clinical trial and must have been on LTOT and on open-label treatment with iNO 75 mcg/kg IBW/hr for at least 4 months
3. Subjects must have achieved ≥ 30 meter improvement in 6MWD after 4, 8 or 12 months of open-label treatment with iNO 75 mcg/kg IBW/hr as compared to either their PULSE PAH-004 Week 2 end of Run-in OR End of Study (EOS)in PULSE-PAH-004.
4. Subjects are willing and considered in the judgement of the Investigator able to use the INOpulse device continuously for up to 24 hours per day
5. Female subjects of childbearing potential must have a negative pregnancy test (serum or urine) at randomization. All female subjects must use an effective method of birth control to avoid pregnancy.

Exclusion Criteria:

1. Subjects with episodes of worsening of PAH in the last 30 days prior to PULSE PAH-007 Baseline/Randomization
2. Subjects that experience Pulmonary Rebound in PULSE-PAH-004
3. Change in dose or types of PAH specific therapies in the last 30 days prior to Baseline/Randomization
4. Subjects who require treatment with riociguat
5. Subjects who early discontinued drug/device usage due to withdrawal of consent or an adverse event requiring termination from treatment in PULSE PAH-004
6. Women who are pregnant
7. The concurrent use of the INOpulse device with a continuous airway pressure (CPAP), Bilevel Positive Airway Pressure (BiPAP, or any other positive pressure device.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Cohort 1: Placebo 99.999% Nitrogen; Randomized Withdrawal Treatment Period Week 1-8: Placebo at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day Long Term Open Label Extension Period: iNO at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day	Drug: Placebo; Placebo at a dose setting of 75 mcg/kg IBW/hr; Other Names: Placebo 99.999% Nitrogen; Drug: iNO; iNO at a dose setting of 75 mcg/kg IBW/hr; Other Names: Inhaled Nitric Oxide
Active Comparator: Cohort 2: iNO 75 mcg/kg IBW/hr; Randomized Withdrawal Treatment Period Week 1-8: iNO at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day Long Term Open Label Extension Period: iNO at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day	Drug: iNO; iNO at a dose setting of 75 mcg/kg IBW/hr; Other Names: Inhaled Nitric Oxide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to clinical worsening during iNO withdrawal for up to 8 weeks	A clinical worsening event is defined as: Death (all-cause mortality); Atrial septostomy; Hospitalization due to worsening of PAH; Need to start additional specific PAH treatment; Decrease of >15% in 6 Minute Walk Distance from randomization into the study; Worsening of WHO Functional Class (e.g., from Class II to Class III or IV, OR Class III to Class IV)	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in clinical worsening events that occur during iNO withdrawal for up to 8 weeks between those treated with iNO ≥ 10 months prior to the start of withdrawal of iNO vs. those treated < 10 months prior to initiation of withdrawal to iNO.	A clinical worsening event is defined as: Death (all-cause mortality); Atrial septostomy; Hospitalization due to worsening of PAH; Need to start additional specific PAH treatment; Decrease of >15% in 6 Minute Walk Distance from randomization into the study; Worsening of WHO Functional Class (e.g., from Class II to Class III or IV, OR Class III to Class IV)	8 weeks

Collaborators and Investigators

• Sponsor: Bellerophon Pulse Technologies
• Collaborators: Worldwide Clinical Trials
• Investigators: Study Director: Ashika Ahmed, MD, Bellerophon Therapeutics

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2018
• Primary Completion (Anticipated): June 1, 2019
• Study Completion (Anticipated): June 1, 2020

Study Registration Dates

• First Submitted: July 6, 2018
• First Submitted That Met QC Criteria: July 25, 2018
• First Posted (Actual): July 27, 2018

Study Record Updates

• Last Update Posted (Estimate): February 20, 2023
• Last Update Submitted That Met QC Criteria: February 17, 2023
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Oxygen therapy; PAH; Inhaled Nitric Oxide; iNO; Long Term Oxygen Therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: PULSE-PAH-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No