Clinical trial • Phase I/II • Cardiology|Rare Disease

PF-07868489 for Pulmonary arterial hypertension

Phase I/II trial of PF-07868489 for Pulmonary arterial hypertension.

Overview

Trial Therapeutic Area
Cardiology|Rare Disease
Trial Disease
Pulmonary arterial hypertension
Trial Stage
Phase I/II
Drug Modality
Peptide/protein/enzyme
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
05-12-2024
First CTIS Authorization Date
09-04-2025

Trial design

Randomised, pf-07868489 placebo; schedule: q4w (every 4 weeks) in part b schema; dose not specified in public documents.-controlled, adaptive Phase I/II trial across 21 sites in Spain, Czechia, Germany and others.

Randomised
Yes
Comparator
PF-07868489 Placebo; schedule: Q4W (every 4 weeks) in Part B schema; dose not specified in public documents.
Adaptive
Yes
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
62
Trial Duration For Participant
168

Eligibility

Recruits 62 No vulnerable populations selected (isVulnerablePopulationSelected=false). Participants must be adults (Participants aged ≥18 years or minimum local age of consent) and must sign informed consent. Assent is not indicated. E-consent methods and country-specific informed consent documents are provided (see consent documents per country)..

Vulnerable Population
No vulnerable populations selected (isVulnerablePopulationSelected=false). Participants must be adults (Participants aged ≥18 years or minimum local age of consent) and must sign informed consent. Assent is not indicated. E-consent methods and country-specific informed consent documents are provided (see consent documents per country).

Inclusion criteria

  • {"criterion_text":"- Participants aged ≥18 years (or the minimum age of consent in accordance with local regulations) at screening who have signed informed consent\n- Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.\n- Documented diagnostic RHC prior to Screening confirming diagnosis of PAH (WHO Group 1 PH) including any of the following subtypes:  Idiopathic or heritable PAH.  Drug- or toxin-induced PAH.  PAH associated with connective tissue disease. * PAH associated with simple, congenital systemic-to-pulmonary shunts at least 1 year following shunt repair. Note: Pre-randomization RHC may fulfil this requirement if local regulation does not permit diagnostic RHC in patient diagnosed and treated since childhood.\n- PAH classified as WHO functional class II or III.\n- Pre-randomization RHC documenting a minimum of PVR ≥ 400 dyn ∙sec/cm5 (5 Wood units); and no contraindication to RHC.  RHC performed within 12 weeks of Screening as part of the participants management of PAH can satisfy this criterion, if the requisite hemodynamic data are available. Otherwise, a RHC needs to be performed prior to randomization. In this case, the RHC should only be performed if the potential participant meets all other inclusion / exclusion criteria for eligibility.\n- PFTs (spirometry) performed as part of the diagnostic evaluation of PAH excluding clinically relevant obstructive or restrictive pulmonary physiology (unless the participant is an active smoker of > 10 cigarettes/equivalent per day or a smoking history ≥10 pack-years, in which case, the PFTs should be done within 6 months prior to Screening). A high-resolution chest computed tomography within 1 year of Screening indicating no more than minimum emphysematous or interstitial changes may be used to satisfy this requirement.\n- Documentation in the participant’s medical history that CTEPH has been excluded.\n- 6MWD ≥ 150 m and ≤ 500 m repeated at least twice during Screening and top two values within 15% of each other, calculated from the highest value.\n- A stable dose of at least 2 SOC PAH vasodilator class therapies for 60 days prior to Screening. a. Titration of IV/SC prostanoids are permitted within 10% of optimal dose in accordance with standard of care.\n- BMI 16 to 40 kg/m2."}

Exclusion criteria

  • {"criterion_text":"- Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.\n- Systolic BP < 90 mmHg during Screening or at baseline.\n- ECG with QTcF >490 msec during Screening or Randomization.\n- Any of the following clinical chemistry values during Screening:  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × ULN (> 5 ULN if solely due to right heart failure) or total bilirubin ≥2 × ULN (For Gilbert’s syndrome, direct bilirubin >ULN [or ≥ 2 x ULN if solely due to right heart failure] is exclusionary)  eGFR < 30 mL/min/1.73 m2 within 30 days prior to randomization or required renal replacement therapy within 90 days of randomization.\n- Hematologic abnormalities defined as: * Platelets ≤ 50,000/mm3\n- Participants with a diagnosis of COPD or other clinically significant lung disease. (eg, bronchiectasis, bronchiolitis, clinically significant emphysema on CT or CxR, pulmonary fibrosis, FEV1 < 60% or moderate to severe ventilatory dysfunction [including both clinically significant, symptomatic restrictive and obstructive physiology that would compromise exercise tolerance], and restrictive lung disease due to other causes than PAH).\n- Stopped receiving pulmonary hypertension chronic general supportive therapy (eg, diuretics, oxygen, anticoagulants, digoxin) within 90 days prior to Screening.\n- History of atrial septostomy within 180 days prior to Screening.\n- Pulmonary capillary wedge pressure (PCWP)/Pulmonary Arterial Occlusion Pressure (PAOP)/ Left Ventricular End Diastolic Pressure (LVEDP) > 15 mmHg on RHC conducted during Screening.\n- History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in investigational product.\n- History of clinically significant (as determined by the investigator) non-PAH related cardiac, endocrine, hematologic, hepatic, immune, metabolic, urologic, pulmonary, neurologic, neuromuscular, dermatologic, psychiatric, renal, and/or other disease that may limit participation in the study.\n- Current use of any prohibited concomitant medication(s) or participants unwilling or unable to use a required concomitant medication(s).\n- Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer) and not concurrently involved in a clinical trial with another investigational product during the study.\n- Uncontrolled systemic hypertension as evidenced by sitting systolic BP > 160 mm Hg or sitting diastolic BP > 100 mm Hg during Screening after a period of rest."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Incidence and severity of AE and SAEs.","definition_or_measurement_approach":"Assessment of adverse events and serious adverse events incidence and severity as reported during the study (safety monitoring)."}
  • {"endpoint_text":"- Change from baseline in vital signs.","definition_or_measurement_approach":"Change from baseline measurements in vital signs (e.g., blood pressure, heart rate) at scheduled visits."}
  • {"endpoint_text":"- Change from baseline in clinical laboratory values.","definition_or_measurement_approach":"Laboratory safety parameters compared to baseline values (clinical chemistry, haematology) at scheduled timepoints."}
  • {"endpoint_text":"- Change from baseline in ECG parameters (heart rate, QT, QTcF, PR, and QRS intervals).","definition_or_measurement_approach":"ECG parameter measurements (heart rate, QT, QTcF, PR, QRS intervals) compared to baseline at scheduled assessments."}
  • {"endpoint_text":"- Change from baseline in Pulmonary Vascular Resistance (PVR) at Week 24","definition_or_measurement_approach":"Change from baseline in PVR measured at Week 24 (hemodynamic assessment via RHC)."}

Secondary endpoints

  • {"endpoint_text":"- PF-07868489 PK parameters after repeat doses; as data permit: Cmin, and t1/2","definition_or_measurement_approach":"Pharmacokinetic parameters after repeat SC dosing including trough concentration (Cmin) and elimination half-life (t1/2) as data permit."}
  • {"endpoint_text":"- Incidence of the development of ADA against PF-07868489 following repeat doses.","definition_or_measurement_approach":"Assessment of anti-drug antibodies (ADA) development incidence following repeat dosing."}
  • {"endpoint_text":"- Change from baseline in NT-proBNP at Week 24","definition_or_measurement_approach":"Change from baseline in blood NT-proBNP concentration measured at Week 24."}
  • {"endpoint_text":"- Percentage of participants with a change from baseline at 24 Week on (6-minute walk distance) (6MWD) of 30 meters or greater.","definition_or_measurement_approach":"Proportion of participants achieving ≥30 meter improvement from baseline in 6-minute walk distance at Week 24."}

Recruitment

Digital Remote Recruitment
Yes
Planned Sample Size
62
Recruitment Window Months
24
Consent Approach
Informed consent must be signed by the participant (Participants aged ≥18 years or minimum local age of consent). E-consent is available (eConsent screenshots and e-consent vendor Signant Health referenced). Country-specific informed consent documents are provided in multiple languages (examples in repository: EN, ES, FR, DE, IT, CS (Czech), NL, EL (Greek)). No pediatric assent procedures are indicated.

Geography

Total Number Of Sites
21
Total Number Of Participants
32

Spain

Earliest CTIS Part Ii Submission Date
18-03-2025
Latest Decision Or Authorization Date
19-03-2026
Processing Time Days
366
Number Of Sites
3
Number Of Participants
5

Sites

Site Name
Hospital Universitario Marques De Valdecilla
Department Name
Pneumology
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 La Paz
Department Name
Pulmonology
Principal Investigator Name
Sergio Alcolea Batres
Principal Investigator Email
alcobatres@yahoo.es
Contact Person Name
Sergio Alcolea Batres
Contact Person Email
alcobatres@yahoo.es
Site Name
Hospital Universitario 12 De Octubre
Department Name
Cardiology
Principal Investigator Name
Pilar Escribano Subias
Principal Investigator Email
pilar.escribano.subias@gmail.com
Contact Person Name
Pilar Escribano Subias

Czechia

Earliest CTIS Part Ii Submission Date
24-03-2025
Latest Decision Or Authorization Date
17-03-2026
Processing Time Days
358
Number Of Sites
2
Number Of Participants
3

Sites

Site Name
Vseobecna Fakultni Nemocnice V Praze
Department Name
Cardiologie
Principal Investigator Name
Pavel Jansa
Principal Investigator Email
pavel.jansa@vfn.cz
Contact Person Name
Pavel Jansa
Contact Person Email
pavel.jansa@vfn.cz
Site Name
Institute For Clinical And Experimental Medicine
Department Name
Cardiology
Principal Investigator Name
Hikmet Al-Hiti
Principal Investigator Email
hial@ikem.cz
Contact Person Name
Hikmet Al-Hiti
Contact Person Email
hial@ikem.cz

Germany

Earliest CTIS Part Ii Submission Date
27-03-2025
Latest Decision Or Authorization Date
19-03-2026
Processing Time Days
357
Number Of Sites
5
Number Of Participants
10

Sites

Site Name
Universitaetsmedizin Greifswald KöR
Department Name
Zentrum für Innere Medizin B Pneumologie/Infektiologie
Principal Investigator Name
Ralf Ewert
Principal Investigator Email
Ralf.Ewert@med.uni-greifswald.de
Contact Person Name
Ralf Ewert
Site Name
Universitaetsklinikum Regensburg AöR
Department Name
Klinik und Poliklinik für Innere Medizin II
Principal Investigator Name
Stefan Stadler
Principal Investigator Email
stefan.stadler@ukr.de
Contact Person Name
Stefan Stadler
Contact Person Email
stefan.stadler@ukr.de
Site Name
Universitaetsklinikum Giessen und Marburg GmbH
Department Name
Medizinische Klinik und Poliklinik II
Principal Investigator Name
Hossein Ardeschir Ghofrani
Contact Person Name
Hossein Ardeschir Ghofrani
Site Name
Technische Universitaet Dresden
Department Name
Medizinische Klinik und Poliklinik I Abteilung für Pneumologie
Principal Investigator Name
Michael Halank
Principal Investigator Email
michael.halank@uniklinikum-dresden.de
Contact Person Name
Michael Halank
Site Name
Thoraxklinik Heidelberg gGmbH
Department Name
Centre for pulmonary hypertension
Principal Investigator Name
Ekkehard Grünig
Principal Investigator Email
Ekkehard.Gruenig@med.uni-heidelberg.de
Contact Person Name
Ekkehard Grünig

Italy

Earliest CTIS Part Ii Submission Date
02-04-2025
Latest Decision Or Authorization Date
18-03-2026
Processing Time Days
350
Number Of Sites
3
Number Of Participants
3

Sites

Site Name
Fondazione IRCCS San Gerardo Dei Tintori
Department Name
U.O.C. Pneumologia
Principal Investigator Name
Giuseppe Paciocco
Principal Investigator Email
giuseppe.paciocco@unimib.it
Contact Person Name
Giuseppe Paciocco
Contact Person Email
giuseppe.paciocco@unimib.it
Site Name
Fondazione IRCCS Policlinico San Matteo
Department Name
U.O di 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
Istituto Mediterraneo Per I Trapianti E Terapie Ad Alta Specializzazione S.r.l. I.S.M.E.T.T. S.r.l.
Department Name
Pulmonology Unit
Principal Investigator Name
Patrizio Vitulo
Principal Investigator Email
pvitulo@ismett.edu
Contact Person Name
Patrizio Vitulo
Contact Person Email
pvitulo@ismett.edu

Belgium

Earliest CTIS Part Ii Submission Date
26-03-2025
Latest Decision Or Authorization Date
16-03-2026
Processing Time Days
355
Number Of Sites
2
Number Of Participants
3

Sites

Site Name
Hopital Erasme
Department Name
Cardiology
Principal Investigator Name
Jean-Luc Vachiery
Principal Investigator Email
jean.luc.vachiery@hubruxelles.be
Contact Person Name
Jean-Luc Vachiery
Site Name
UZ Leuven
Department Name
Pulmonology
Principal Investigator Name
Marion Delcroix
Principal Investigator Email
marion.delcroix@uzleuven.be
Contact Person Name
Marion Delcroix
Contact Person Email
marion.delcroix@uzleuven.be

France

Earliest CTIS Part Ii Submission Date
27-06-2025
Latest Decision Or Authorization Date
18-03-2026
Processing Time Days
264
Number Of Sites
3
Number Of Participants
5

Sites

Site Name
Centre Hospitalier Universitaire De Saint Etienne
Department Name
Service de Médecine Vasculaire et Thérapeutique
Principal Investigator Name
Laurent Bertoletti
Principal Investigator Email
laurent.bertoletti@chu-st-etienne.fr
Contact Person Name
Laurent Bertoletti
Site Name
Centre Hospitalier Regional Et Universitaire De Brest
Department Name
Department of Internal Medicine and Pneumology
Principal Investigator Name
Cécile Tromeur
Principal Investigator Email
cecile.tromeur@chu-brest.fr
Contact Person Name
Cécile Tromeur
Contact Person Email
cecile.tromeur@chu-brest.fr
Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
Service de Pneumologie Physiologie - CHUGA
Principal Investigator Name
Bruno Degano
Principal Investigator Email
bdegano@chu-grenoble.fr
Contact Person Name
Bruno Degano
Contact Person Email
bdegano@chu-grenoble.fr

Greece

Earliest CTIS Part Ii Submission Date
07-02-2025
Latest Decision Or Authorization Date
24-04-2026
Processing Time Days
441
Number Of Sites
3
Number Of Participants
3

Sites

Site Name
Onassis Cardiac Surgery Center
Department Name
Cardiology
Principal Investigator Name
Dimitrios Tsiapras
Principal Investigator Email
dtsiapras@hotmail.com
Contact Person Name
Dimitrios Tsiapras
Contact Person Email
dtsiapras@hotmail.com
Site Name
University General Hospital Of Thessaloniki Ahepa
Department Name
1st Cardiology Clinic
Principal Investigator Name
George Giannakoulas
Principal Investigator Email
g.giannakoulas@gmail.com
Contact Person Name
George Giannakoulas
Contact Person Email
g.giannakoulas@gmail.com
Site Name
University General Hospital Attikon General Hospital Of West Attica H Agia Varvara
Department Name
2nd Critical Care Department
Principal Investigator Name
Iraklis Tsagkaris
Principal Investigator Email
itsagkaris@med.uoa.gr
Contact Person Name
Iraklis Tsagkaris
Contact Person Email
itsagkaris@med.uoa.gr

Sponsor

Primary sponsor

Full Name
Pfizer Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Syneos Health Hellas Single Member S.A.
Responsibilities
study start up activities, study conduct, monitoring responsibilities

Third parties

  • {"country":"Greece","full_name":"Syneos Health Hellas Single Member S.A.","duties_or_roles":"study start up activities, study conduct, monitoring responsibilities","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Turnkey Export Compliance UK Ltd","duties_or_roles":"Importer of Records","organisation_type":"Industry"}
  • {"country":"United States","full_name":"Ancillare LP","duties_or_roles":"Equipment provision","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"Central Laboratory","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"eCOA, e-consent","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Illingworth Research Group Limited","duties_or_roles":"Patient reimbursement/accommodation","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"clinical trial imaging services","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
PF-07868489
Active Substance
PF-07868489
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS USE
Route
Subcutaneous
Authorisation Status
MIA IMP11510/00002
Orphan Designation
Yes
Frequency
Q4W (every 4 weeks)
Investigational Product Name
PF-07868489 Placebo
Modality
Other
Orphan Designation
Yes
Frequency
Q4W (placebo administered per Part B schema)
Combination Treatment
Yes

Related trials

Other published trials that may interest you.