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

Pulmonary Arterial Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05649748
• Other study ID #: INS1009-203
• Secondary ID: 2022-001951-1820
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: March 7, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: June 2024
• Source: Insmed Incorporated
• Contact: Insmed Medical Information
• Phone: 1-844-446-7633
• Email: medicalinformation[@]insmed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Treprostinil Palmitil
Administered by oral inhalation, using a Plastiape capsule-based dry powder inhaler.
• Placebo
Administered by oral inhalation using a Plastiape capsule-based dry powder inhaler

Locations

Country	Name	City	State
Argentina	ARG001	Córdoba
Argentina	ARG004	Córdoba
Argentina	ARG009	Quilmes	Buenos Aires
Argentina	ARG006	Rosario	Santa Fe
Argentina	ARG007	San Miguel de Tucuman	Tucuman
Austria	AUT002	Linz	Oberösterreich
Austria	AUT001	Wien
Brazil	BRA004	Belo Horizonte	Minas Gerais
Brazil	BRA006	Porto Alegre	Rio Grande Do Sul
Denmark	DNK001	Aarhus	Central Jutland
Germany	GER005	Heidelberg	Baden-Württemberg
Germany	GER002	Lübeck	Schleswig-Holstein
Italy	ITA005	Monza
Italy	ITA002	Pavia	Lombardia
Japan	JPN002	Okayama-Shi	Okayama
Japan	JPN005	Sapporo-shi	Hokkaido
Japan	JPN003	Suita-Shi	Osaka
Malaysia	MYS005	Alor Setar	Kedah
Malaysia	MYS002	Kuantan	Pahang
Malaysia	MYS004	Sungai Buloh	Selangor
Mexico	MEX001	Monterrey	Nuevo León
Mexico	MEX004	San Luis Potosi
Philippines	PHL002	Makati City
Serbia	SRB001	Belgrade
Serbia	SRB003	Belgrade
Spain	ESP001	Santander
Spain	ESP003	Sevilla
United Kingdom	GBR001	Bath	Avon
United States	USA001	Chicago	Illinois
United States	USA006	Chicago	Illinois
United States	USA016	Dallas	Texas
United States	USA102	New York	New York
United States	USA011	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Insmed Incorporated

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Brazil,  Denmark,  Germany,  Italy,  Japan,  Malaysia,  Mexico,  Philippines,  Serbia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Relative Change From Pre-OLE Baseline in 6MWD		Pre-OLE baseline (baseline of the lead-in TPIP study), Months 6, 12, 18, and 24
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Plasma Concentration Levels of Treprostinil Palmitil (TP) and Treprostinil (TRE)		OLE Baseline (Day 1), Months 6, 12, 18, and 24