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

Phase 3

Withdrawn

• Conditions: Pulmonary Arterial Hypertension
• Interventions: Drug: Placebo; Drug: iNO

• Registration Number: NCT03602781
• Lead Sponsor: Bellerophon Pulse Technologies

Brief Summary

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

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 Timeline

• Status Verified: 2018-07
• Study First Submitted: 2018-07-06
• Study First Submitted QC: 2018-07-25
• Study First Posted: 2018-07-27
• Study Start: 2018-08
• Primary Completion: 2019-06
• Study Completion: 2020-06
• Last Update Submitted: 2023-02-17
• Last Update Posted: 2023-02-21

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1: Placebo 99.999% Nitrogen	Placebo	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
Cohort 1: Placebo 99.999% Nitrogen	iNO	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
Cohort 2: iNO 75 mcg/kg IBW/hr	iNO	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

Primary Outcome Measures

Name	Time	Method
Time to clinical worsening during iNO withdrawal for up to 8 weeks	8 weeks	A clinical worsening event is defined as: 1. Death (all-cause mortality); 2. Atrial septostomy; 3. Hospitalization due to worsening of PAH; 4. Need to start additional specific PAH treatment; 5. Decrease of \>15% in 6 Minute Walk Distance from randomization into the study; 6. Worsening of WHO Functional Class (e.g., from Class II to Class III or IV, OR Class III to Class IV)

Secondary Outcome Measures

Name	Time	Method
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.	8 weeks	A clinical worsening event is defined as: 1. Death (all-cause mortality); 2. Atrial septostomy; 3. Hospitalization due to worsening of PAH; 4. Need to start additional specific PAH treatment; 5. Decrease of \>15% in 6 Minute Walk Distance from randomization into the study; 6. Worsening of WHO Functional Class (e.g., from Class II to Class III or IV, OR Class III to Class IV)

Trial Locations

Locations (4)

Bluhm Cardiovascular Institute, Clinical Trials Unit; 🇺🇸 Chicago, Illinois, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Peter Lougheed Centre; 🇨🇦 Calgary, Alberta, Canada

Toronto General Hospital, University Health Network; 🇨🇦 Toronto, Ontario, Canada