An Extension Study of Treprostinil Palmitil Inhalation Powder (TPIP) for Pulmonary Arterial Hypertension (PAH)

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: Treprostinil Palmitil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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-19. 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. Participants who currently inhale marijuana (recreational or medical). Note: Other inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treprostinil Palmitil Inhalation Powder (TPIP)<br>Participants who are not transitioning immediately from other TPIP studies: INS1009-201 (NCT04791514), INS1009-202 (NCT05147805) and other lead-in studies, will be administered TPIP, once daily (QD), at a starting dose of 80 micrograms (μg), up-titrated to the highest tolerated dose between 80 μg and 640 μg during 3-week titration period. The overall treatment period will be 24 months. Participants who are transitioning immediately from a randomized blinded lead-in TPIP study and who previously received: TPIP- will be administered placebo QD (80 μg up to achieved TPIP dose from previous study) along with the achieved TPIP dose from previous study in a blinded manner during 3-week titration period. Placebo- will be administered TPIP QD (80 μg up to achieved placebo dose from previous study) along with the achieved placebo dose from previous study in a blinded manner during 3-week titration period. The overall treatment period will be 24 months. | Drug: Treprostinil Palmitil<br>* Administered by oral inhalation, using a Plastiape capsule-based dry powder inhaler.<br>* Other names: INS1009;Drug: Placebo<br>* Administered by oral inhalation using a Plastiape capsule-based dry powder inhaler<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experience at Least one Treatment Emergent Adverse Event (TEAE) and TEAEs by Severity |  | From screening up to last follow up visit (Up to approximately 26 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | Annualized clinical worsening event rate is defined as the total number of clinical worsening events that occurred during the treatment period divided by the total number of participant-years during the treatment period. Clinical worsening events are one of the following: All-cause death, or onset of TEAE with a fatal outcome occurring ≤ 14 days after study drug discontinuation; Hospitalization for right heart failure (for > 48 hours), heart-lung or lung transplant, or atrial septostomy; Addition (or increase in dose) of specified PAH-specific medications; Combined occurrence of events including ≥20% decrease in 6MWD, worsening WHO/NYHA functional capacity class, and appearance of or worsening of signs/symptoms of right heart failure from baseline. | OLE Baseline (Day 1) up to Month 24 or early discontinuation | 
| Plasma Concentration Levels of Treprostinil Palmitil (TP) and Treprostinil (TRE) |  | OLE Baseline (Day 1), Months 6, 12, 18, and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treprostinil Palmitil