COMPLETED

Efficacy and Safety of Seralutinib in Adult Subjects With PAH (PROSERA)

Conditions

Pulmonary Arterial Hypertension seralutinib GB002 PROSERA

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The primary objective of the study is to determine the effect of seralutinib on improving exercise capacity in subjects with WHO Group 1 PAH who are FC II or III. The secondary objective for this trial is to determine time to clinical worsening.

Official Title

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Oral Inhalation of Seralutinib for the Treatment of Pulmonary Arterial Hypertension (PAH)

Quick Facts

Study Start:2023-12-28

Study Completion:2025-12-22

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:COMPLETED

Study ID

NCT05934526

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 75 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Adult subjects aged 18 to 75 years. 2. Body mass index (BMI) ≥ 15 kg/m\^2 and ≤ 40 kg/m\^2. 3. Diagnosis of PAH classified by one of the following: 1. Idiopathic PAH (IPAH) or heritable PAH (HPAH). 2. PAH associated with connective tissue disease (CTD-APAH); PAH associated with anorexigen or PAH associated with methamphetamine use. 3. Congenital heart disease with simple systemic to pulmonary shunt at least 1 year after surgical repair. 4. 6MWDs ≥ 150 meters and ≤ 475 meters during Screening prior to randomization. 5. WHO FC II or III. 6. US Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) Lite 2 Risk Score ≥ 5 OR NT-proBNP ≥ 300 ng/L OR PVR ≥ 800 dyne s/cm\^5. 7. Cardiac catheterization within the screening period, or a standard of care right heart catheterization (RHC) (with pressure wave forms available for review) up to 48 weeks prior to Screening. 1. Mean pulmonary arterial pressure (mPAP) \> 20 mmHg (at rest), AND 2. Pulmonary vascular resistance (PVR) ≥ 400 dyne·s/cm\^5, AND 3. Pulmonary capillary wedge pressure (PCWP) or left ventricle end-diastolic pressure (LVEDP) ≤ 15 mmHg. 8. Treatment with at least one allowed background PAH disease-specific medication prior to Screening. 1. Subjects receiving treatment with endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, guanylate cyclase stimulators, and/or prostacyclin analogues or prostacyclin receptor agonists are eligible only if on a stable dose for at least 12 weeks prior to and throughout Screening. 2. Subjects receiving treatment with sotatercept are eligible only if on a stable dose of sotatercept for at least 24 weeks prior to and throughout Screening, with a RHC performed during Screening (or within 2 weeks prior to Screening). 9. Pulmonary function tests (PFTs) at Screening or completed no more than 12 weeks prior to Screening. 10. Women of childbearing potential (WOCBP) must have a negative pregnancy test at Screening and on Day 1 before first administration of Investigational Product (IP). 11. WOCBP who are not abstinent and intend to be sexually active with a non-sterilized male partner must be willing to use a highly effective method of contraception from consent through 30 days following the last administration of IP. 12. Male subjects: Non-sterilized male subjects who are not abstinent and intend to be sexually active with a female partner of childbearing potential must use a male condom from consent through 90 days after the last dose of IP.	1. Evidence of chronic thromboembolic disease or acute pulmonary embolism. 2. Uncontrolled systemic hypertension as evidenced by systolic blood pressure \> 160 mm Hg or diastolic blood pressure \> 100 mm Hg. 3. Systolic blood pressure \< 90 mm Hg during Screening. 4. WHO Pulmonary Hypertension Group 2 - 5. 5. Human immunodeficiency virus (HIV)-associated PAH, schistosomiasis associated PAH, PAH associated with portal hypertension, or pulmonary veno-occlusive disease (PVOD). 6. Recent history of left-sided heart disease and/or clinically significant cardiac disease within 48 weeks of Screening. 7. Left ventricular ejection fraction (LVEF) ≤ 50% within 24 weeks of Screening. 8. Hemodynamically significant valvular heart disease or uncontrolled symptomatic coronary disease. 9. History of atrial septostomy. 10. Uncontrolled atrial fibrillation or paroxysmal atrial fibrillation. 11. Untreated severe obstructive sleep apnea. 12. Hepatic dysfunction defined as Child-Pugh Class A or higher, or as evidenced by one of the following at Screening: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 1.5 x upper limit of normal (ULN) or total bilirubin ≥ 1.5 x ULN. 13. Severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or IP administration (eg, history of intracranial hemorrhage, recurrent syncope). 14. Any musculoskeletal disease, injury, or any other disease that limits evaluation of 6MWT. 15. Initiation of an exercise program for cardiopulmonary rehabilitation within 12 weeks prior to Screening or planned during the study. 16. Pregnant or nursing or intends to become pregnant during the duration of the study. 17. Body weight \< 37 kg at Screening. 18. Estimated glomerular filtration rate (eGFR) \< 45 mL/min/1.73m\^2 Hemoglobin (Hgb) concentration \< 8.5 g/dL at Screening. 19. Evidence of active or latent Human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C, or tuberculosis (TB) infection at Screening. 20. Prior/concurrent treatment with tyrosine kinase inhibitors or activin signaling inhibitors: 1. Tyrosine kinase inhibitors, other than Janus kinase inhibitors approved for systemic autoimmune rheumatic diseases, within 12 weeks prior to Screening. 2. Activin signaling inhibitors within 5 half-lives prior to Screening. 21. Requirement of IV inotropes (ie, levosimendan, dopamine, dobutamine, milrinone, norepinephrine) or IV diuretics for more than 24 hours within 4 weeks prior to Screening. 22. Subjects currently receiving oral anticoagulants (ie, warfarin/other vitamin K antagonists or direct-acting oral anticoagulants \[DOACs\]) if any of the following criteria are met: 23. Prior participation in seralutinib studies and/or prior treatment with seralutinib. 24. Currently participating in or has participated in a study of an investigational agent or has used an investigational device for the treatment of PAH within 12 weeks or 5 half-lives of the investigational agent, whichever is longer, prior to Screening. 25. Current use of inhaled tobacco- or nicotine-containing products (including e-vapor products) and/or inhaled marijuana. 26. Current alcohol use disorder based on the opinion of the Investigator, and/or a positive test for drugs of abuse. 27. Subjects with a history of severe milk protein allergy or known intolerance to lactose. 28. QT interval corrected for heart rate using Fridericia's formula (QTcF) of \> 500 msec. 29. Have any other condition or reason that, in the opinion of the Investigator or in the opinion of the Sponsor's Medical Monitor (MM) (or designee) in consultation with the Investigator, would prohibit the subject from participating in the study.

Inclusion Criteria

Exclusion Criteria

1. Adult subjects aged 18 to 75 years.
2. Body mass index (BMI) ≥ 15 kg/m\^2 and ≤ 40 kg/m\^2.
3. Diagnosis of PAH classified by one of the following:
1. Idiopathic PAH (IPAH) or heritable PAH (HPAH).
2. PAH associated with connective tissue disease (CTD-APAH); PAH associated with anorexigen or PAH associated with methamphetamine use.
3. Congenital heart disease with simple systemic to pulmonary shunt at least 1 year after surgical repair.
4. 6MWDs ≥ 150 meters and ≤ 475 meters during Screening prior to randomization.
5. WHO FC II or III.
6. US Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) Lite 2 Risk Score ≥ 5 OR NT-proBNP ≥ 300 ng/L OR PVR ≥ 800 dyne s/cm\^5.
7. Cardiac catheterization within the screening period, or a standard of care right heart catheterization (RHC) (with pressure wave forms available for review) up to 48 weeks prior to Screening.
1. Mean pulmonary arterial pressure (mPAP) \> 20 mmHg (at rest), AND
2. Pulmonary vascular resistance (PVR) ≥ 400 dyne·s/cm\^5, AND
3. Pulmonary capillary wedge pressure (PCWP) or left ventricle end-diastolic pressure (LVEDP) ≤ 15 mmHg.
8. Treatment with at least one allowed background PAH disease-specific medication prior to Screening.
1. Subjects receiving treatment with endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, guanylate cyclase stimulators, and/or prostacyclin analogues or prostacyclin receptor agonists are eligible only if on a stable dose for at least 12 weeks prior to and throughout Screening.
2. Subjects receiving treatment with sotatercept are eligible only if on a stable dose of sotatercept for at least 24 weeks prior to and throughout Screening, with a RHC performed during Screening (or within 2 weeks prior to Screening).
9. Pulmonary function tests (PFTs) at Screening or completed no more than 12 weeks prior to Screening.
10. Women of childbearing potential (WOCBP) must have a negative pregnancy test at Screening and on Day 1 before first administration of Investigational Product (IP).
11. WOCBP who are not abstinent and intend to be sexually active with a non-sterilized male partner must be willing to use a highly effective method of contraception from consent through 30 days following the last administration of IP.
12. Male subjects: Non-sterilized male subjects who are not abstinent and intend to be sexually active with a female partner of childbearing potential must use a male condom from consent through 90 days after the last dose of IP.

1. Evidence of chronic thromboembolic disease or acute pulmonary embolism.
2. Uncontrolled systemic hypertension as evidenced by systolic blood pressure \> 160 mm Hg or diastolic blood pressure \> 100 mm Hg.
3. Systolic blood pressure \< 90 mm Hg during Screening.
4. WHO Pulmonary Hypertension Group 2 - 5.
5. Human immunodeficiency virus (HIV)-associated PAH, schistosomiasis associated PAH, PAH associated with portal hypertension, or pulmonary veno-occlusive disease (PVOD).
6. Recent history of left-sided heart disease and/or clinically significant cardiac disease within 48 weeks of Screening.
7. Left ventricular ejection fraction (LVEF) ≤ 50% within 24 weeks of Screening.
8. Hemodynamically significant valvular heart disease or uncontrolled symptomatic coronary disease.
9. History of atrial septostomy.
10. Uncontrolled atrial fibrillation or paroxysmal atrial fibrillation.
11. Untreated severe obstructive sleep apnea.
12. Hepatic dysfunction defined as Child-Pugh Class A or higher, or as evidenced by one of the following at Screening: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 1.5 x upper limit of normal (ULN) or total bilirubin ≥ 1.5 x ULN.
13. Severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or IP administration (eg, history of intracranial hemorrhage, recurrent syncope).
14. Any musculoskeletal disease, injury, or any other disease that limits evaluation of 6MWT.
15. Initiation of an exercise program for cardiopulmonary rehabilitation within 12 weeks prior to Screening or planned during the study.
16. Pregnant or nursing or intends to become pregnant during the duration of the study.
17. Body weight \< 37 kg at Screening.
18. Estimated glomerular filtration rate (eGFR) \< 45 mL/min/1.73m\^2 Hemoglobin (Hgb) concentration \< 8.5 g/dL at Screening.
19. Evidence of active or latent Human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C, or tuberculosis (TB) infection at Screening.
20. Prior/concurrent treatment with tyrosine kinase inhibitors or activin signaling inhibitors:
1. Tyrosine kinase inhibitors, other than Janus kinase inhibitors approved for systemic autoimmune rheumatic diseases, within 12 weeks prior to Screening.
2. Activin signaling inhibitors within 5 half-lives prior to Screening.
21. Requirement of IV inotropes (ie, levosimendan, dopamine, dobutamine, milrinone, norepinephrine) or IV diuretics for more than 24 hours within 4 weeks prior to Screening.
22. Subjects currently receiving oral anticoagulants (ie, warfarin/other vitamin K antagonists or direct-acting oral anticoagulants \[DOACs\]) if any of the following criteria are met:
23. Prior participation in seralutinib studies and/or prior treatment with seralutinib.
24. Currently participating in or has participated in a study of an investigational agent or has used an investigational device for the treatment of PAH within 12 weeks or 5 half-lives of the investigational agent, whichever is longer, prior to Screening.
25. Current use of inhaled tobacco- or nicotine-containing products (including e-vapor products) and/or inhaled marijuana.
26. Current alcohol use disorder based on the opinion of the Investigator, and/or a positive test for drugs of abuse.
27. Subjects with a history of severe milk protein allergy or known intolerance to lactose.
28. QT interval corrected for heart rate using Fridericia's formula (QTcF) of \> 500 msec.
29. Have any other condition or reason that, in the opinion of the Investigator or in the opinion of the Sponsor's Medical Monitor (MM) (or designee) in consultation with the Investigator, would prohibit the subject from participating in the study.

Contacts and Locations

Principal Investigator

Richard Aranda, MD

STUDY_DIRECTOR

Gossamer Bio Inc.

Study Locations (Sites)

University of Alabama at Birmingham

Birmingham, Alabama, 35233

United States

Valley Advanced Lung Diseases Institute

Fresno, California, 93711

United States

Keck Medical Center of USC

Los Angeles, California, 90033

United States

Dept of Veterans Affairs Greater Los Angeles Healthcare System

Los Angeles, California, 90073

United States

University of California, Irvine Medical Center

Orange, California, 92868

United States

UC Davis Health

Sacramento, California, 95817

United States

Stanford Healthcare

Stanford, California, 94305

United States

Winchester Center for Lung Disease

New Haven, Connecticut, 06519

United States

The George Washington University Medical Faculty Associates

Washington D.C., District of Columbia, 20037

United States

University of Florida Clinical Research Center

Gainesville, Florida, 32610

United States

Mayo Clinic

Jacksonville, Florida, 32224

United States

Piedmont Physicians Pulmonary & Sleep Medicine of Buckhead

Atlanta, Georgia, 30309

United States

Emory University

Atlanta, Georgia, 30322

United States

Northside Hospital Laboratory - Atlanta

Atlanta, Georgia, 30342

United States

UI Health Hospital

Chicago, Illinois, 60612

United States

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242

United States

University of Kansas Medical Center

Kansas City, Kansas, 66160

United States

Norton Hospital

Louisville, Kentucky, 40202

United States

Tufts Medical Center

Boston, Massachusetts, 02111

United States

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

University of Michigan

Ann Arbor, Michigan, 48109

United States

M Health Fairview University of Minnesota Medical Center - East Bank

Minneapolis, Minnesota, 55455

United States

University of Missouri

Columbia, Missouri, 65212

United States

Washington University School of Medicine

St Louis, Missouri, 63110

United States

University of Nebraska Medical Center

Omaha, Nebraska, 68198

United States

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, 87131

United States

NYU Langone Health

New York, New York, 10016

United States

University of Rochester Medical Center

Rochester, New York, 14642

United States

UNC Hospitals

Chapel Hill, North Carolina, 27514

United States

Duke University Medical Center - Duke South

Durham, North Carolina, 27710

United States

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219

United States

Cleveland Clinic Foundation

Cleveland, Ohio, 44195

United States

INTEGRIS Cardiovascular Physicians, LLC

Oklahoma City, Oklahoma, 73112

United States

Oregon Health & Science University

Portland, Oregon, 97239

United States

The Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104

United States

Temple Heart and Vascular Institute (Outpatient Clinic)

Philadelphia, Pennsylvania, 19140

United States

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213

United States

Rhode Island Hospital

Providence, Rhode Island, 02903

United States

Medical University of South Carolina - Nexus Research Center

Charleston, South Carolina, 29425

United States

UT Southwestern Medical Center

Dallas, Texas, 75390

United States

CHI St. Luke's Health Baylor College of Medicine Medical Center

Houston, Texas, 77030

United States

Houston Methodist Outpatient Center

Houston, Texas, 77030

United States

Baylor Scott & White Medical Center - The Heart Hospital

Plano, Texas, 75024

United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229

United States

Intermountain Medical Center

Murray, Utah, 84107

United States

University of Utah Hospital

Salt Lake City, Utah, 84132

United States

Inova Fairfax Medical Campus

Falls Church, Virginia, 22042

United States

Pulmonary Associates of Richmond, Inc.

Richmond, Virginia, 23230

United States

Advocate Aurora Health-Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, 53215

United States

Froedtert Hospital/Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

United States

Collaborators and Investigators

Sponsor: GB002, Inc.

Richard Aranda, MD, STUDY_DIRECTOR, Gossamer Bio Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-12-28

Study Completion Date2025-12-22

Study Record Updates

Study Start Date2023-12-28

Study Completion Date2025-12-22

Terms related to this study

Keywords Provided by Researchers

seralutinib
GB002
PROSERA

Additional Relevant MeSH Terms

Pulmonary Arterial Hypertension