An Open-Label Extension Study to Assess the Safety, Tolerability, and Effectiveness of the Long-Term Use of Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Arterial Hypertension
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Pulmonary Arterial Hypertension
- Sponsor
- Insmed Incorporated
- Enrollment
- 91
- Locations
- 60
- Primary Endpoint
- Number of Participants Who Experience at Least one Treatment Emergent Adverse Event (TEAE) and TEAEs by Severity
- Status
- Active, not recruiting
- Last Updated
- 18 days ago
Overview
Brief Summary
The primary purpose of the study is to evaluate the safety and tolerability of the long-term use of TPIP in participants with PAH from studies INS1009-201 (NCT04791514), INS1009-202 (NCT05147805) and other lead-in studies of TPIP in participants with PAH.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male and female participants who completed end of treatment study visit in Study INS1009-201, INS1009-202, or any other lead-in PAH TPIP study. Participants for whom the OLE study was not available at the time of their completion of the lead-in study are eligible for enrolment within one year of their lead-in end of treatment visit.
- •Complete baseline screening assessments to confirm eligibility to participate if more than 30 days have elapsed since the end of the study visit in Study INS1009-201, INS1009-202, or any other lead-in PAH TPIP study.
Exclusion Criteria
- •Initiation of parenteral administration of prostacyclin analogues (eg, TRE, epoprostenol) since the completion of studies INS1009-201, INS1009-202 or other TPIP studies. Initiation of inhaled prostacyclin analogues (eg, TRE \[Tyvaso\] or iloprost) and oral prostacyclin analogues (eg, TRE \[Orenitram\]) or receptor agonists (eg, selexipag) are permitted if stopped 24 hours prior to the start of study drug administration.
- •Any new ventricular or supraventricular tachyarrhythmia except for paroxysmal atrial fibrillation and any new symptomatic bradycardia.
- •New-onset of heart disease including left ventricular ejection fraction (LVEF) ≤40% or clinically significant valvular, constrictive, or symptomatic atherosclerotic heart disease (eg, stable angina, myocardial infarction, etc).
- •New evidence of thromboembolic disease as assessed by ventilation/perfusion (VQ) scan, pulmonary angiography, or pulmonary computed tomography (CT) scan.
- •Active and current symptomatic coronavirus disease 2019 (COVID-19) or previous severe disease and/or hospitalization due to COVID-
- •Interval organ transplantation.
- •New active liver disease or hepatic dysfunction.
- •Interval malignancy with exception of completely treated in situ carcinoma of the cervix and completely treated non-metastatic squamous or basal cell carcinoma of the skin.
- •Use of any investigational drug/device or participation in any investigational study within 30 days prior to screening, not including TPIP of the lead-in study.
- •Current use of cigarettes (as defined by Centers for Disease Control and Prevention \[CDC\]) or e-cigarettes: An adult who has smoked at least 100 cigarettes in his or her lifetime, who smokes either every day or some days.
Arms & Interventions
Treprostinil Palmitil Inhalation Powder (TPIP)
Participants who are not transitioning immediately from other TPIP studies:INS1009-201(NCT04791514), INS1009-202(NCT05147805) and other lead-in studies, will be given TPIP, once daily (QD), starting with 80 micrograms (μg), up-titrated to highest tolerated dose between 80 μg and 640 μg during 3-week titration period that maybe increased upto maximum dose of 1280 μg QD post initial titration, per investigator's assessment. Overall treatment period=24 months. Participants transitioning immediately from randomized blinded lead-in TPIP study and who previously received: 1. TPIP- will be given placebo QD(80 μg upto achieved TPIP dose from previous study)along with achieved TPIP dose from previous study in blinded manner during 3-week titration period. 2. Placebo- will be given TPIP QD (80 μg up to achieved placebo dose from previous study)along with achieved placebo dose from previous study in blinded manner during 3-week titration period.Overall treatment period=24 months.
Intervention: Placebo
Treprostinil Palmitil Inhalation Powder (TPIP)
Participants who are not transitioning immediately from other TPIP studies:INS1009-201(NCT04791514), INS1009-202(NCT05147805) and other lead-in studies, will be given TPIP, once daily (QD), starting with 80 micrograms (μg), up-titrated to highest tolerated dose between 80 μg and 640 μg during 3-week titration period that maybe increased upto maximum dose of 1280 μg QD post initial titration, per investigator's assessment. Overall treatment period=24 months. Participants transitioning immediately from randomized blinded lead-in TPIP study and who previously received: 1. TPIP- will be given placebo QD(80 μg upto achieved TPIP dose from previous study)along with achieved TPIP dose from previous study in blinded manner during 3-week titration period. 2. Placebo- will be given TPIP QD (80 μg up to achieved placebo dose from previous study)along with achieved placebo dose from previous study in blinded manner during 3-week titration period.Overall treatment period=24 months.
Intervention: Treprostinil Palmitil
Outcomes
Primary Outcomes
Number of Participants Who Experience at Least one Treatment Emergent Adverse Event (TEAE) and TEAEs by Severity
Time Frame: From screening up to last follow up visit (Up to approximately 26 months)
Secondary Outcomes
- Change From Pre-OLE Baseline in the Concentration of N-Terminal Fragment B-Type Natriuretic Peptide (NT-proBNP) in Blood(Pre-OLE baseline (baseline of the lead-in TPIP study), Months 6, 12, 18, and 24)
- Change From Pre-OLE Baseline in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2.0 Score(Pre-OLE baseline (baseline of the lead-in TPIP study), Months 6, 12, 18, and 24)
- Change From Pre-OLE Baseline in New York Heart Association/ World Health Organization (NYHA/WHO) Functional Capacity Class(Pre-OLE baseline (baseline of the lead-in TPIP study), Months 6, 12, 18, and 24)
- Annualized Clinical Worsening Event Rate(OLE Baseline (Day 1) up to Month 24 or early discontinuation)
- Absolute Change From Pre-Open Label Extension (OLE) Baseline in 6-Minute Walk Distance (6MWD)(Pre-OLE baseline (baseline of the lead-in TPIP study), Months 6, 12, 18, and 24)
- Relative Change From Pre-OLE Baseline in 6MWD(Pre-OLE baseline (baseline of the lead-in TPIP study), Months 6, 12, 18, and 24)
- Plasma Concentration Levels of Treprostinil Palmitil (TP) and Treprostinil (TRE)(OLE Baseline (Day 1), Months 6, 12, 18, and 24)