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

Study Overview
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Brief Summary
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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.

Official Title
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A PHASE 1, 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 REPEAT DOSES IN PARTICIPANTS WITH PULMONARY ARTERIAL HYPERTENSION

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: PF-07868489
* Drug: Placebo for PF-07868489


Participation Criteria
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Eligibility Criteria
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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 32 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Part A is a sequential study. Part B is a parallel group study.
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 281 | 
| Number of Participants With Change From Baseline in Laboratory Tests Results | Part B | Baseline up to Day 281 | 
| Number of Participants With Vital Sign Abnormalities | Part B | Baseline up to Day 281 | 
| Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters | Part B | Baseline up to Day 281 | 

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 | 20 days | 
| Minimum Observed Plasma Trough Concentration (Cmin) | repeat doses | week 4 | 
| Plasma Decay Half-Life (t1/2) | repeat doses | 20 days | 
| Incidence of Anti-Drug Antibody (ADA) | repeated doses | Baseline and up to week 40 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary, high lung artery pressure