Clinical trial • Phase II • Respiratory
TREPROSTINIL PALMITIL for Pulmonary arterial hypertension
Phase II trial of TREPROSTINIL PALMITIL for Pulmonary arterial hypertension. open-label, none/not specified-controlled, adaptive. 70 participants.
Overview
- Trial Therapeutic Area
- Respiratory
- Trial Disease
- Pulmonary arterial hypertension
- Trial Stage
- Phase II
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 14-08-2024
- First CTIS Authorization Date
- 13-09-2024
Trial design
open-label, none/not specified-controlled, adaptive Phase II trial in Belgium, Austria, Denmark and others.
- Open Label
- Yes
- Comparator
- None/Not specified
- Adaptive
- True, dose-titration and dose escalation are employed: an initial 3-week titration period to achieve optimal dosing for each participant, with possible further dose adjustments based on safety, tolerability, and medical need.
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 70
- Trial Duration For Participant
- 748
Eligibility
Recruits 70 Vulnerable population selected. Participants must be capable of giving signed informed consent. Country-specific subject information and informed consent forms are provided, including specific ICFs for pregnant participants, pregnant partner/newborn data; consent is provided by the participant (no assent procedures for minors are described)..
- Vulnerable Population
- Vulnerable population selected. Participants must be capable of giving signed informed consent. Country-specific subject information and informed consent forms are provided, including specific ICFs for pregnant participants, pregnant partner/newborn data; consent is provided by the participant (no assent procedures for minors are described).
Inclusion criteria
- {"criterion_text":"- Participants who completed the end of treatment visit in Study INS1009 201, Study 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.\n- 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, Study INS1009 202, or any other lead in PAH TPIP in study.\n- Capable of giving signed informed consent that includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol."}
Exclusion criteria
- {"criterion_text":"- 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.\n- QTcF interval > 480 ms on resting ECG at screening, not including participants with right bundle branch block (RBBB) leading to a prolongation of the QRS.\n- Any new ventricular or supraventricular tachyarrhythmia except for paroxysmal atrial fibrillation and any new symptomatic bradycardia.\n- 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).\n- New evidence of thromboembolic disease as assessed by VQ scan, pulmonary angiography, or pulmonary CT scan.\n- Active and current symptomatic COVID-19 or previous severe disease and/or hospitalization due to COVID-19\n- Current use of cigarettes (as defined by 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\n- Participants who currently inhale marijuana (recreational or medical).\n- Participants who experienced any hypersensitivity or adverse drug reaction or were withdrawn early/discontinued in a previous PAH TPIP study, which, in the opinion of the Investigator, could indicate that continued treatment with TPIP may present an unreasonable risk for the participant."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Frequency and severity of TEAEs during the study","definition_or_measurement_approach":"Recorded frequency and severity of treatment-emergent adverse events (TEAEs) reported during the study."}
Secondary endpoints
- {"endpoint_text":"- Change from pre-OLE baseline to Month 6, Month 12, Month 18, and Month 24 in 6MWD (absolute and relative), in the concentration of NT proBNP in blood, in the REVEAL Lite 2.0 score, in NYHA/WHO functional capacity class.","definition_or_measurement_approach":"Change from pre-OLE baseline measured at Months 6, 12, 18, and 24 for 6-minute walk distance (absolute and relative), blood NT-proBNP concentration, REVEAL Lite 2.0 score, and NYHA/WHO functional class."}
- {"endpoint_text":"- Annualized rate of clinical worsening events defined as 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","definition_or_measurement_approach":"Annualized rate of clinical worsening events where events include all-cause death or fatal TEAE within ≤14 days after study drug discontinuation, hospitalization for right heart failure (>48 hours), heart–lung or lung transplant, or atrial septostomy."}
- {"endpoint_text":"- Addition (or increase in dose) of specified PAH-specific medications. Combined occurrence of events including a 20% decrease in 6MWD, worsening WHO/NYHA functional capacity class, and appearance of or worsening of signs/symptoms of right heart failure. Annualized clinical worsening event rate 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.","definition_or_measurement_approach":"Composite endpoint including addition/increase of PAH-specific medications, 20% decrease in 6MWD, worsening WHO/NYHA class, or new/worsened signs of right heart failure; annualized clinical worsening rate = total events ÷ participant-years of treatment."}
- {"endpoint_text":"- Plasma concentration levels of TP and TRE","definition_or_measurement_approach":"Measurement of plasma concentrations of treprostinil palmitil (TP) and treprostinil (TRE) using specified bioanalytical assays (plasma PK sampling as per protocol)."}
Recruitment
- Planned Sample Size
- 70
- Recruitment Window Months
- 55
- Consent Approach
- Informed consent is provided by the participant (inclusion criterion: capable of giving signed informed consent). Country-specific subject information and ICFs are provided (examples: German ICFs for Austria/Germany, Danish ICF for Denmark, Spanish ICF for Spain, Italian ICFs for Italy, Dutch/English/French ICFs for Belgium). Specific ICFs are available for pregnant participants and pregnant partners/newborn data where applicable.
Geography
- Total Number Of Sites
- 12
- Total Number Of Participants
- 23
Belgium
- Earliest CTIS Part Ii Submission Date
- 13-09-2024
- Latest Decision Or Authorization Date
- 29-10-2025
- Processing Time Days
- 411
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Hopital Erasme
- Department Name
- Pneumology
- Principal Investigator Name
- Jean-Luc Vachiery
- Principal Investigator Email
- jean.luc.vachiery@hubruxelles.be
- Contact Person Name
- Jean-Luc Vachiery
- Contact Person Email
- jean.luc.vachiery@hubruxelles.be
Austria
- Earliest CTIS Part Ii Submission Date
- 15-09-2024
- Latest Decision Or Authorization Date
- 11-06-2025
- Processing Time Days
- 269
- Number Of Sites
- 2
- Number Of Participants
- 2
Sites
- Site Name
- Ordensklinikum Linz GmbH
- Department Name
- Interne 2 – Kardiologie, Angiologie & interne Intensivmedizin
- Principal Investigator Name
- Regina Steringer-Mascherbauer
- Principal Investigator Email
- regina.steringer-mascherbauer@ordensklinikum.at
- Contact Person Name
- Regina Steringer-Mascherbauer
- Contact Person Email
- regina.steringer-mascherbauer@ordensklinikum.at
- Site Name
- Medical University Of Vienna
- Department Name
- Klinik für Innere Medizin II, Klin. Abteilung für Kardiologie, Ambulanz für Lungenhochdruck
- Principal Investigator Name
- Irene Lang
- Principal Investigator Email
- irene.lang@meduniwien.ac.at
- Contact Person Name
- Irene Lang
- Contact Person Email
- irene.lang@meduniwien.ac.at
Denmark
- Earliest CTIS Part Ii Submission Date
- 13-09-2024
- Latest Decision Or Authorization Date
- 28-10-2025
- Processing Time Days
- 410
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Aarhus Universitetshospital
- Department Name
- Department of Cardiology
- Principal Investigator Name
- Søren Mellemkjær
- Principal Investigator Email
- soren.mellemkjaer@rm.dk
- Contact Person Name
- Søren Mellemkjær
- Contact Person Email
- soren.mellemkjaer@rm.dk
Germany
- Earliest CTIS Part Ii Submission Date
- 16-09-2024
- Latest Decision Or Authorization Date
- 30-10-2025
- Processing Time Days
- 409
- Number Of Sites
- 3
- Number Of Participants
- 6
Sites
- Site Name
- Krankenhaus Neuwittelsbach
- Department Name
- Fachklinik für Innere Medizin
- Principal Investigator Name
- Hanno Leuchte
- Principal Investigator Email
- Prof.Leuchte@krankenhaus-neuwittelsbach.de
- Contact Person Name
- Hanno Leuchte
- Contact Person Email
- Prof.Leuchte@krankenhaus-neuwittelsbach.de
- Site Name
- Universitaetsklinikum Schleswig-Holstein AöR
- Department Name
- Medizinische Klinik III
- Principal Investigator Name
- Daniel Drömann
- Principal Investigator Email
- daniel.droemann@uksh.de
- Contact Person Name
- Daniel Drömann
- Contact Person Email
- daniel.droemann@uksh.de
- Site Name
- Thoraxklinik Heidelberg gGmbH
- Department Name
- Zentrum für pulmonale Hypertonie
- Principal Investigator Name
- Ekkehard Grünig
- Principal Investigator Email
- ekkehard.gruenig@med.uni-heidelberg.de
- Contact Person Name
- Ekkehard Grünig
- Contact Person Email
- ekkehard.gruenig@med.uni-heidelberg.de
Spain
- Earliest CTIS Part Ii Submission Date
- 16-09-2024
- Latest Decision Or Authorization Date
- 29-10-2025
- Processing Time Days
- 408
- Number Of Sites
- 2
- Number Of Participants
- 6
Sites
- Site Name
- Hospital Universitario Marques De Valdecilla
- Department Name
- Pneumology Service
- Principal Investigator Name
- Jose Manuel Cifrian Martinez
- Principal Investigator Email
- josemanuel.cifrian@scsalud.es
- Contact Person Name
- Jose Manuel Cifrian Martinez
- Contact Person Email
- josemanuel.cifrian@scsalud.es
- Site Name
- Hospital Universitario Virgen De La Macarena
- Department Name
- Pneumology Service
- Principal Investigator Name
- Alejandro Recio Mayoral
- Principal Investigator Email
- jandrorm@hotmail.com
- Contact Person Name
- Alejandro Recio Mayoral
- Contact Person Email
- jandrorm@hotmail.com
Italy
- Earliest CTIS Part Ii Submission Date
- 16-10-2024
- Latest Decision Or Authorization Date
- 03-11-2025
- Processing Time Days
- 383
- Number Of Sites
- 3
- Number Of Participants
- 5
Sites
- Site Name
- Fondazione IRCCS Policlinico San Matteo
- Department Name
- UOC Cardiologia
- Principal Investigator Name
- Stefano Ghio
- Principal Investigator Email
- s.ghio@smatteo.pv.it
- Contact Person Name
- Stefano Ghio
- Contact Person Email
- s.ghio@smatteo.pv.it
- Site Name
- Azienda Ospedaliero-Universitaria Policlinico Umberto I
- Department Name
- Dipartimento di Malattie dell’Apparato Cardiovascolare e Respiratorio
- Principal Investigator Name
- Carmine Dario Vizza
- Principal Investigator Email
- dario.vizza@uniroma1.it
- Contact Person Name
- Carmine Dario Vizza
- Contact Person Email
- dario.vizza@uniroma1.it
- Site Name
- Fondazione IRCCS San Gerardo Dei Tintori
- Department Name
- Centro di Ricerca di Fase I
- Principal Investigator Name
- Giuseppe Paciocco
- Principal Investigator Email
- giuseppe.paciocco@unimib.it
- Contact Person Name
- Giuseppe Paciocco
- Contact Person Email
- giuseppe.paciocco@unimib.it
Sponsor
Primary sponsor
- Full Name
- Insmed Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Parexel International (IRL) Limited
- Responsibilities
- sponsorDuties code 10
- Name
- PPD International Holdings LLC / PPD Development LP
- Responsibilities
- Clinical operations and multiple trial support functions (sponsorDuties codes include 1,2,5,8,12,13,15; value examples: Site Payments, Clinical Chemistry/Haematology services)
- Name
- Primevigilance Limited
- Responsibilities
- Pharmacovigilance (sponsorDuties code 8)
- Name
- Almac Clinical Technologies LLC
- Responsibilities
- Supplier/technology services (sponsorDuties code 3)
- Name
- Medidata Solutions Inc.
- Responsibilities
- Data platform/support (sponsorDuties code 7)
Third parties
- {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties: code 7","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Colorado Prevention Center","duties_or_roles":"sponsorDuties: code 15 (value: 6MWTS)","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"sponsorDuties: code 10","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Primevigilance Limited","duties_or_roles":"sponsorDuties: code 8","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"sponsorDuties: code 3","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Alliance Pharma Inc.","duties_or_roles":"sponsorDuties: code 15 (value: PK samples)","organisation_type":"Pharmaceutical company"}
- {"country":"Belgium","full_name":"PPD International Holdings LLC","duties_or_roles":"sponsorDuties: code 15 (value: Clinical Chemistry, Clinical Haematology, Serology/ endocrinology)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"sponsorDuties: codes 1, 12, 13, 15 (value: Site Payments), 2, 5, 8","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"PPD Development LP (duplicate entry in list)","duties_or_roles":"sponsorDuties: codes 1,12,13,15,2,5,8","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- TREPROSTINIL PALMITIL INHALATION POWDER
- Active Substance
- TREPROSTINIL PALMITIL
- Modality
- Small molecule
- Routes Of Administration
- INHALATION USE
- Route
- INHALATION
- Authorisation Status
- prodAuthStatus: 1
- Frequency
- QD (once daily) - as described: open-label TPIP QD
- Maximum Dose
- 640 µg per day
- Investigational Product Name
- TREPROSTINIL PALMITIL INHALATION POWDER
- Active Substance
- TREPROSTINIL PALMITIL
- Modality
- Small molecule
- Routes Of Administration
- INHALATION USE
- Route
- INHALATION
- Authorisation Status
- prodAuthStatus: 1
- Frequency
- QD (once daily)
- Maximum Dose
- 640 µg per day
- Investigational Product Name
- TREPROSTINIL PALMITIL INHALATION POWDER
- Active Substance
- TREPROSTINIL PALMITIL
- Modality
- Small molecule
- Routes Of Administration
- INHALATION USE
- Route
- INHALATION
- Authorisation Status
- prodAuthStatus: 1
- Frequency
- QD (once daily)
- Maximum Dose
- 640 µg per day
- Investigational Product Name
- Placebo (inhalation powder capsules) containing 1 of 3 dosage strengths of TPIP (80 μg, 160 μg, or 320 μg)
- Modality
- Other
- Dose Levels
- 80 μg; 160 μg; 320 μg (placebo capsules containing one of these dosage strengths)
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