A Study to Learn About the Study Medicine Called PF-07868489 in Healthy Adult People and in People With Pulmonary Arterial Hypertension

A PHASE 1 / 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF SINGLE ESCALATING DOSES OF PF-07868489 IN HEALTHY ADULT PARTICIPANTS AND, ADDITIONALLY, CLINICAL ACTIVITY OF REPEAT DOSES IN PARTICIPANTS WITH PULMONARY ARTERIAL HYPERTENSION

The purpose of the study is to learn how the study medicine called PF-07868489 is tolerated and acts in healthy adult people and people with pulmonary arterial hypertension (PAH).

Part A:

An investigator- and participant-blind, sponsor-open, placebo-controlled, single ascending dose study to assess the safety, tolerability, and pharmacokinetics (PK) of PF-07868489 in healthy adult participants.

Part B:

A 24-week, randomized, double blind, placebo-controlled study to assess the safety, tolerability, PK, and pharmacodynamics (PD) of PF-07868489 in adult participants with PAH.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: PF-07868489; Drug: Placebo for PF-07868489

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Wesley Research Institute
    • Auchenflower, Queensland, Australia, 4066
      • Pulmonary Hypertension Research Queensland Pty Ltd
• Belgium
  • Bruxelles-capitale, Région de
    • Brussels, Bruxelles-capitale, Région de, Belgium, 1070
      • Université Libre de Bruxelles - Hôpital Erasme
  • Vlaams-brabant
    • Leuven, Vlaams-brabant, Belgium, 3000
      • UZ Leuven
• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial People's Hospital
  • Hunan
    • Changsha, Hunan, China, 410011
      • The Second Xiangya Hospital Of Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital Southeast University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200433
      • Shanghai Pulmonary Hospital
• Czechia
  • Prague, Czechia, 12808
    • Všeobecná fakultní nemocnice v Praze
• France
  • Finistère
    • Brest, Finistère, France, 29200
      • CHRU de Brest
    • Brest, Finistère, France, 29609
      • CHRU de Brest
  • Pays de la Loire Region
    • Saint Priest En Jarez, Pays de la Loire Region, France, 42270
      • Centre Hospitalier Universitaire de Saint Étienne - Hôpital Nord
• Germany
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69126
      • Thoraxklinik-Heidelberg gGmbH
  • Bavaria
    • Regensburg, Bavaria, Germany, 93053
      • Universitätsklinikum Regensburg
  • Hesse
    • Giessen, Hesse, Germany, 35392
      • UKGM Gießen/Marburg
  • Mecklenburg-Vorpommern
    • Greifswald, Mecklenburg-Vorpommern, Germany, 17475
      • Universitätsmedizin Greifswald
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus, Technischen Universitaet Dresden
• Italy
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo
• Japan
  • Okayama, Japan, 701-1154
    • National Hospital Organization Okayama Medical Center
  • Hyōgo
    • Kobe, Hyōgo, Japan, 650-0017
      • Kobe University Hospital
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 216-8511
      • St. Marianna University Hospital
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
      • Tohoku University Hospital
• South Korea
  • Incheon-gwangyeoksi [incheon]
    • Namdong-gu, Incheon-gwangyeoksi [incheon], South Korea, 21565
      • Gachon University Gil Medical Center
  • Seoul-teukbyeolsi [seoul]
    • Seoul, Seoul-teukbyeolsi [seoul], South Korea, 03080
      • Seoul National University Hospital
    • Seoul, Seoul-teukbyeolsi [seoul], South Korea, 06351
      • Samsung Medical Center
    • Seoul, Seoul-teukbyeolsi [seoul], South Korea, 03722
      • Severance Hospital, Yonsei University Health System
• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Comunidad de
    • Madrid, Madrid, Comunidad de, Spain, 28046
      • Hospital Universitario La Paz
• United Kingdom
  • London, CITY of
    • London, London, CITY of, United Kingdom, W12 0HS
      • Hammersmith Hospital
• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
    • Costa Mesa, California, United States, 92627
      • UCI Health - Costa Mesa
    • Orange, California, United States, 92868
      • University of California, Irvine Medical Center
    • Orange, California, United States, 92868
      • UCI Health Center for Innovative Health Therapies (CIHT)
    • San Francisco, California, United States, 94143
      • UCSF Helen Diller Medical Center at Parnassus Heights
    • San Francisco, California, United States, 94117
      • UCSF Health St. Mary's Hospital
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Unc Hospitals
    • Chapel Hill, North Carolina, United States, 27514
      • Eastowne 100 Medical Office Building
    • Chapel Hill, North Carolina, United States, 27514
      • Eastowne Medical Office Building - Clinical Research Unit
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Health - Eastowne Medical Office
    • Morrisville, North Carolina, United States, 27560
      • Investigational Drug Services Pharmacy
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina - Radiology
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina - Nexus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria Part A:

• overtly healthy
• Body mass index (BMI) of 16 to 32 kg/m2; and a total body weight >50 kg.

Key Exclusion Criteria Part A:

• clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, infections or allergic disease.
• smoking more than 10 cigarettes (or equivalent) per day or smoking history ≥10 pack-years.

Key Inclusion Criteria Part B:

• diagnosis of pulmonary arterial hypertension (PAH)
• stable dose of standard of care PAH vasodilators
• BMI 16 to 40 kg/m2; and a total body weight >45 kg.
• 6MWD ≥ 150 and ≤ 450.
• Pre-randomization RHC documenting a minimum of PVR ≥ 400 dyn ∙sec/cm5.

Key Exclusion Criteria Part B:

• Any medical or psychiatric condition or laboratory abnormality.
• Stopped receiving pulmonary hypertension chronic general supportive therapy 90 days prior to Day 1.
• Pulmonary capillary wedge pressure > 15 mmHg on right heart catheterization (RHC) conducted during Screening.
• History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in investigational product.
• Major surgery within 8 weeks prior to randomization.
• Participants who smoke more than 10 cigarettes (or equivalent) per day or has a smoking history ≥10 pack-years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-07868489; single subcutaneous injection (Part A); 6 subcutaneous injections at regular intervals (Part B)	Drug: PF-07868489; Experimental Treatment
Placebo Comparator: Placebo; single subcutaneous injection (Part A); 6 subcutaneous injections at regular intervals (Part B)	Drug: Placebo for PF-07868489; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Part A	Baseline up to Day 113.
Number of Participants With Change From Baseline in Laboratory Tests Results	Part A	Baseline up to Day 113
Number of Participants With Vital Sign Abnormalities	Part A	Baseline up to Day 113
Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters	Part A	Baseline up to Day 113
Number of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Part B	Baseline up to Day 253
Number of Participants With Change From Baseline in Laboratory Tests Results	Part B	Baseline up to Day 253
Number of Participants With Vital Sign Abnormalities	Part B	Baseline up to Day 253
Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters	Part B	Baseline up to Day 253
Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week24	repeated doses	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast)	single dose	Pre dose, 8, 12, 24, 48,72,96,168,336 hours post dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)	single dose	Pre dose, 8, 12, 24, 48,72,96,168,336 hours post dose
Maximum Observed Plasma Concentration (Cmax)	single dose	Pre dose, 8, 12, 24, 48,72,96,168,336 hours post dose
Time to Reach Maximum Observed Plasma Concentration (Tmax)	single dose	4-7 days
Incidence of Anti-Drug Antibody (ADA)	single dose	Baseline and up to week 16
Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) Concentration at Week24	repeated doses	Baseline, Week 24
Plasma Decay Half-Life (t1/2)	single dose	Day 113
Minimum Observed Plasma Trough Concentration (Cmin)	repeat doses	Day 253
Plasma Decay Half-Life (t1/2)	repeat doses	Day 253
Incidence of Anti-Drug Antibody (ADA)	repeated doses	Baseline and up to Day 253
6MWD	repeated doses	Baseline, Week 24

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2023
• Primary Completion (Actual): July 31, 2026
• Study Completion (Actual): July 31, 2026

Study Registration Dates

• First Submitted: November 14, 2023
• First Submitted That Met QC Criteria: November 14, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Actual): August 21, 2026
• Last Update Submitted That Met QC Criteria: August 19, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: pulmonary; high lung artery pressure
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Pulmonary Arterial Hypertension
• Other Study ID Numbers: C5001001; 2024-514064-17-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No