A Study to Learn How the Study Medicine Called PF-07868489 is Tolerated and Acts in Healthy Adult People and People With Pulmonary Arterial Hypertension

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

23 May 2025 → ongoing

Decision date (initial)

2025-04-09

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Pfizer Inc., 66 Hudson Boulevard East, New York, NY 10001, USA

External identifiers

EU CT number

2024-514064-17-00

ClinicalTrials.gov

NCT06137742

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Pharmacodynamic

To evaluate the safety and tolerability of repeat SC doses of PF-07868489 in participants with PAH.

To evaluate the effects of repeated PF-07868489 dosing on PVR in participants with PAH

Secondary objectives 4

1. To characterize serum exposure following repeat SC doses of PF-07868489 in participants with PAH.
2. To evaluate the immunogenicity profile of PF-07868489 following repeat SC doses in participants with PAH.
3. To evaluate the effects of repeated PF-07868489 dosing on 6MWD in participants with PAH
4. To characterize change in blood concentration of NTproBNP following repeat SC dose administration of PF-07868489 in participants with PAH.

Conditions and MedDRA coding

Pulmonary Arterial Hypertension

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut

Plan to share IPD

Yes

IPD plan description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Participants aged ≥18 years (or the minimum age of consent in accordance with local regulations) at screening who have signed informed consent
2. 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.
3. PAH classified as WHO functional class II or III.
4. 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.
5. 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.
6. Documentation in the participant’s medical history that CTEPH has been excluded.
7. 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.
8. 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.
9. BMI 16 to 40 kg/m2.
10. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

Exclusion criteria 14

1. 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.
2. Stopped receiving pulmonary hypertension chronic general supportive therapy (eg, diuretics, oxygen, anticoagulants, digoxin) within 90 days prior to Screening.
3. History of atrial septostomy within 180 days prior to Screening.
4. Pulmonary capillary wedge pressure (PCWP)/Pulmonary Arterial Occlusion Pressure (PAOP)/ Left Ventricular End Diastolic Pressure (LVEDP) > 15 mmHg on RHC conducted during Screening.
5. History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in investigational product.
6. 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.
7. Current use of any prohibited concomitant medication(s) or participants unwilling or unable to use a required concomitant medication(s).
8. 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.
9. 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.
10. Systolic BP < 90 mmHg during Screening or at baseline.
11. ECG with QTcF >490 msec during Screening or Randomization.
12. 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.
13. Hematologic abnormalities defined as: * Platelets ≤ 50,000/mm3
14. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Incidence and severity of AE and SAEs.
2. Change from baseline in vital signs.
3. Change from baseline in clinical laboratory values.
4. Change from baseline in ECG parameters (heart rate, QT, QTcF, PR, and QRS intervals).
5. Change from baseline in Pulmonary Vascular Resistance (PVR) at Week 24

Secondary endpoints 4

1. PF-07868489 PK parameters after repeat doses; as data permit: Cmin, and t1/2
2. Incidence of the development of ADA against PF-07868489 following repeat doses.
3. Change from baseline in NT-proBNP at Week 24
4. Percentage of participants with a change from baseline at 24 Week on (6-minute walk distance) (6MWD) of 30 meters or greater.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 7

Locations

7 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 46 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications