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

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)

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Placebo; Device: Generic Dry Powder Inhaler; Drug: Seralutinib

• Study Type: Interventional
• Enrollment (Actual): 390
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Instituto Cardiovascular de Buenos Aires
  • Buenos Aires, Argentina
    • Cardiología Palermo
  • Corrientes, Argentina
    • Instituto de Cardiologia de Corrientes Juana Francisca Cabral
  • Córdoba, Argentina
    • Hospital Privado Centro Medico de Cordoba S.A.
  • Quilmes, Argentina
    • Instituto de Investigaciones Clinicas Quilmes
  • Rosario, Argentina
    • Sanatorio Parque S.A.
  • Río Cuarto, Argentina
    • Instituto Medico Rio Cuarto
  • Santa Fe, Argentina
    • Hospital Provincial Dr. Jose Maria Cullen
• Australia
  • Auchenflower, Australia
    • Wesley Research Institute
  • Hobart, Australia
    • Royal Hobart Hospital
  • Kingswood, Australia
    • Nepean Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3065
      • St Vincent's Hospital
• Austria
  • Linz, Austria
    • Religious Hospital Linz GmbH
  • Vienna, Austria
    • AKH-Vienna Medical Univesity of Vienna Internal Medicine II-Cardiology
• Belgium
  • Anderlecht, Belgium
    • Hopital Erasme
  • Leuven, Belgium
    • University Hospitals of Leuven (Campus Gasthuisberg)
• Brazil
  • Belo Horizonte, Brazil
    • Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa
  • Blumenau, Brazil
    • Complexo de Prevencao, Diagnostico, Terapia e Reabilitacao Respiratoria - Hospital Dia do Pulmao
  • Porto Alegre, Brazil
    • Irmandade da Santa Casa de Misericordia de Porto Alegre
  • Porto Alegre, Brazil
    • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS
  • São Paulo, Brazil
    • Instituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
  • São Paulo, Brazil
    • Núcleo de Gestão de Pesquisa/Hospital São Paulo - SPDM/UNIFESP
• Canada
  • Calgary, Canada
    • Peter Lougheed Center
  • Toronto, Canada
    • University Health Network
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Science Centre - Victoria Hospital
    • Ottawa, Ontario, Canada, K1Y4W7
      • University of Ottawa Heart Institute
• Chile
  • Santiago, Chile
    • Centro de investigación Clinica UC-CICUC
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile, 7500587
      • Enroll Spa
• Colombia
  • Bogotá, Colombia
    • Fundación Abood Shaio
  • Bogotá, Colombia
    • Fundacion Neumologica Colombiana
• Czechia
  • Prague, Czechia
    • Institut klinické a experimentální medicíny
  • Prague, Czechia
    • Všeobecná fakultní nemocnice v Praze Il. interní klinika kardiologie a angiologie VFN a 1.LF UK Centrum pro plicní hypertenzi
• Denmark
  • Aarhus, Denmark
    • Aarhus Universitetshospital, Department of Cardiology
  • Copenhagen, Denmark
    • Rigshospitalet, Department of Cardiology
• France
  • Le Kremlin-Bicêtre, France
    • CHU Bicêtre
  • Lille, France
    • Institut Coeur Poumon
  • Montpellier, France
    • CHU de Montpellier
  • Nice, France
    • Hopital PASTEUR
  • Poitiers, France
    • CHU De Poitiers
  • Strasbourg, France
    • Hopitaux universitaires de Strasbourg
  • Vandœuvre-lès-Nancy, France
    • Centre Hospitalier Universitaire - Hôpital d´Adultes de Brabois
• Germany
  • Berlin, Germany
    • DRK Kliniken Berlin Westend
  • Cologne, Germany
    • Zentrum fur Pulmona le Hypertonie, Klini k Ill fur lnnere Medizin (Kardiologie, Pneumologie, lnternlstische lntensiv medizin), Herzzentrum der Universitat zu Koln
  • Dresden, Germany
    • Universitatsklinikum Dresden, Medizinische Klinik / Pneumologisches Studiensekretariat
  • Giessen, Germany
    • Universitatsklinikum Giessen und Marburg GmbH Zentrum fur Innere Medizin, Med. Klinik und Poliklinik II Studienambulanz fur Pulmonale Hypertonie
  • Greifswald, Germany
    • Universitätsklinikum Greifswald Klinik und Poliklinik für Innere Medizin B
  • Halle, Germany
    • Universitätsklinikum Halle (Saale) / Martin-Luther-Universität Halle- Wittenberg, Universitätsklinik und Poliklinik für Innere Medizin I
  • Heidelberg, Germany
    • Thoraxklinik Heidelberg gGmbH am Universitätsklinikum Heidelberg Zentrum für pulmonale Hypertonie
  • Munich, Germany
    • Krankenhaus Neuwittelsbach
  • München, Germany
    • Klinikum der LMU Medizinische Klinik und Poliklinik V
  • Würzburg, Germany
    • Klinikum Wurzburg Mitte gGmbH Medizinische Klinik mit Schwerpunkt Pneumologie und Beatmungsmedizin
• Greece
  • Athens, Greece
    • "Evangelismos" General Hospital, 1st Department of Clinical Care & Pulmonary Hypertension Clinic
  • Athens, Greece
    • ATTIKON University Hospital, 2nd Critical Care Department
  • Kallithea, Greece
    • Onassis Cardiac Surgery Center
  • Thessaloniki, Greece
    • AHEPA University General Hospital of Thessaloniki, 1st Cardiology Clinic
• Ireland
  • Dublin, Ireland
    • Mater Misericordiae University Hospital, Respiratory Department
• Israel
  • Haifa, Israel, 3436212
    • Lady Davis Carmel Medical Center
  • Kfar Saba, Israel, 4428164
    • Meir Medical Center
  • Petah Tikva, Israel
    • Rabin Medical Center
  • Ramat Gan, Israel
    • The Chaim Sheba Medical Center
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center
• Italy
  • Bologna, Italy
    • IRCCS Azienda Ospedaliero Universitaria Di Bologna Policlinico 5 Orsola Malpighi - U.O.C. Cardiologia
  • Naples, Italy
    • Azienda Ospedaliera Dei Colli - Ospedale Monaldi Centro per la Diagnosi e Terapia dell'Ipertensione Polmonare
  • Pavia, Italy
    • Fondazione IRCCS Policlinico San Matteo - U.O. di Cardiologia
  • Rome, Italy
    • Azienda Ospealiero Universitaria Policlinico Umberto I - Dipartamento di Scienze Cliniche Internistiche Anestesiologiche e Cardiovascolari - VIII Padglione
  • Trieste, Italy
    • Azienda Sanitaria Universitaria Giuliano Isontina /ASUGI - Ospedale di Cattinara - Cardiovascular Department Coronary Intensive Care Unit
• Japan
  • Fukuoka, Japan
    • Kyushu University Hospital
  • Kurume, Japan
    • Kurume University Hospital
  • Nagoya, Japan
    • Nagoya University Hospital
  • Okayama, Japan
    • NHO Okayama Medical Center
  • Shinjuku-Ku, Japan
    • Keio University Hospital
  • Suita, Japan
    • National Cerebral and Cardiovascular Center
  • Tokyo, Japan
    • Kyorin University Hospital
  • Tokyo, Japan
    • University of Tokyo Hospital
• Latvia
  • Riga, Latvia
    • Pauls Stradins Clinical University Hospital
• Lithuania
  • Kaunas, Lithuania
    • Hospital of Lithuanian University of Health Sciences Kauno klinikos
• Mexico
  • Mexico City, Mexico
    • Instituto Nacional de Cardiologia Ignacio Chavez
  • Monterrey, Mexico
    • Hospital Universitario Dr. José Eleuterio González Centro de Prevención y Rehabilitación de Enfermedades Pulmonares Crónicas
  • Monterrey, Mexico
    • Unidad de Investigación Clínica en Medicina, S.C.
• Netherlands
  • Amsterdam, Netherlands
    • Amsterdam UMC, location VUmc
  • Rotterdam, Netherlands
    • Erasmus MC
• Poland
  • Krakow, Poland
    • Krakowski Szpital Specjalistyczny Im. Św. Jana Pawła II Oddział Kliniczny Chorób Serca i Naczyń z Pododdziałem Intensywnego Nadzoru Kardiologicznego
  • Otwock, Poland
    • Europejskie Centrum Zdrowia Otwock Sp. z o.o. Szpital irn. Fryderyka Chopina Oddzial Kardiologiczny
• Portugal
  • Coimbra, Portugal
    • Centro Hospitalar e Universitario de Coimbra
  • Lisbon, Portugal
    • Centro Hospitalar Universitário Lisboa Norte, EPE - Hospital Pulido Valente
  • Porto, Portugal
    • Centro Hospitalar Universitário de Santo António
• Romania
  • Bucharest, Romania
    • Emergency Institute of Cardiovascular Diseases "Prof. Dr. C.C. Iliescu" Bucharest, Cardiology 2
  • Cluj-Napoca, Romania
    • "Niculae Stanciolu" Emergency Heart Institute for Cardivascular Diseases
  • Cluj-Napoca, Romania
    • Mediprax Centrum S.R.L
  • Târgu Mureş, Romania
    • Targu-Mures Emergency Clinical County Hospital, Internal Medicine II
• Saudi Arabia
  • Riyadh, Saudi Arabia
    • King Faisal Specialist Hospital and Research Center
  • Riyadh, Saudi Arabia
    • King Fahad Medical City
• Serbia
  • Belgrade, Serbia
    • Institute for Cardiovascular Diseases "Dedinje" Clinic for Cardiology
  • Belgrade, Serbia
    • University Clinical Centre of Serbia, Cardiology Clinic
• Singapore
  • Singapore, Singapore
    • National Heart Centre Singapore
  • Singapore, Singapore
    • National University Heart Centre Singapore
• South Korea
  • Seoul, South Korea
    • Asan Medical Center
  • Seoul, South Korea
    • Samsung Medical Center
  • Seoul, South Korea
    • Seoul National University Hospital
  • Seoul, South Korea
    • Severance Hospital, Yonsei University Health System Seoul
  • Seoul, South Korea
    • The Catholic University of Korea, Seoul St. Mary´s Hospital
• Spain
  • Barcelona, Spain
    • Hospital Clínic i Provincial
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Majadahonda, Spain
    • Hospital Universitario Puerta de Hierro Majadahonda
  • Marbella, Spain
    • Hospital Costa del Sol
  • Palma de Mallorca, Spain
    • Hospital Universitario Son Espases
  • Santander, Spain
    • Hospital Universitario Marqués de Valdecilla
  • Seville, Spain
    • Hospital Universitario Virgen del Rocio
  • Toledo, Spain
    • Hospital Universitario de Toledo
• United Kingdom
  • Cambridge, United Kingdom
    • Royal Papworth Hospital NHS Foundation Trust
  • Clydebank, United Kingdom
    • Golden Jubilee National Hospital, Agamemnon Street
  • London, United Kingdom
    • Royal Free Hospital
  • London, United Kingdom
    • Hammersmith Hospital
  • London, United Kingdom
    • Royal Brompton Hospital, Pulmonary Hypertension Service, Sydney Street
  • Newcastle, United Kingdom
    • Freeman Hospital
  • Sheffield, United Kingdom
    • Sheffield Clinical Research Facility, Royal Hallamshire Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Fresno, California, United States, 93711
      • Valley Advanced Lung Diseases Institute
    • Los Angeles, California, United States, 90033
      • Keck Medical Center of USC
    • Los Angeles, California, United States, 90073
      • Dept of Veterans Affairs Greater Los Angeles Healthcare System
    • Orange, California, United States, 92868
      • University of California, Irvine Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Health
    • Stanford, California, United States, 94305
      • Stanford Healthcare
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Winchester Center for Lung Disease
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20037
      • The George Washington University Medical Faculty Associates
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Clinical Research Center
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Atlanta, Georgia, United States, 30309
      • Piedmont Physicians Pulmonary & Sleep Medicine of Buckhead
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital Laboratory - Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60612
      • UI Health Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals & Clinics
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • M Health Fairview University of Minnesota Medical Center - East Bank
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Health Sciences Center
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Hospitals
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center - Duke South
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • INTEGRIS Cardiovascular Physicians, LLC
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Hospital of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple Heart and Vascular Institute (Outpatient Clinic)
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina - Nexus Research Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • CHI St. Luke's Health Baylor College of Medicine Medical Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Outpatient Center
    • Plano, Texas, United States, 75024
      • Baylor Scott & White Medical Center - The Heart Hospital
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Medical Campus
    • Richmond, Virginia, United States, 23230
      • Pulmonary Associates of Richmond, Inc.
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital/Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Advocate Aurora Health-Aurora St. Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion 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.

Exclusion Criteria:

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:

    a. History within 24 weeks of Screening of: i. Syncope, or ii. Symptomatic bleeding in a critical area or organ iii. Intramuscular with compartment syndrome, or iv. Bleeding causing a fall in hemoglobin levels of 1.24 mmol/L (20 g/L or greater) or more, or v. Bleeding leading to a transfusion of 2 U or more of whole blood or red blood cells.

    b. History of central nervous system pathology.

    c. History of clinically significant (massive) hemoptysis.

    d. If on warfarin/other vitamin K antagonist, uncontrolled International normalized ratio (eg, INR > 3) as assessed.

    e. Platelet count < 150 x 10^9/L at Screening.

    f. Concomitant use of antiplatelet agents.

    g. CTD-APAH

    h. Concomitant use of sotatercept.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo inhaled orally twice daily (BID) up to 48 weeks	Drug: Placebo; Matching capsule containing placebo; Device: Generic Dry Powder Inhaler; Generic dry powder inhaler for seralutinib or placebo delivery
Experimental: Seralutinib 90 mg; Seralutinib inhaled orally BID up to 48 weeks	Device: Generic Dry Powder Inhaler; Generic dry powder inhaler for seralutinib or placebo delivery; Drug: Seralutinib; Capsule containing seralutinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in distance achieved on the six-minute walk test (6MWT), six-minute walk distance (Δ6MWD) from baseline to Week 24	Baseline to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first event of Clinical Worsening from first dose of Investigational Product (IP) through end of study		Baseline to 48 weeks
Proportion of subjects who achieve all of the following components of clinical improvement at Week 24, in the absence of clinical worsening:	Improvement from baseline in World Health Organization (WHO) functional class (FC) or maintenance of WHO FC II; Decrease from baseline in N-terminal pro b-type natriuretic peptide (NT-proBNP) of ≥ 30% or decrease and maintenance at < 300 ng/L; Increase from baseline in 6MWD of ≥ 10% or ≥ 30 m	Baseline to 24 weeks
Change in NT-proBNP from baseline to Week 24		Baseline to 24 weeks
Proportion of subjects with ≥ 1 point decrease from baseline in US Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) Lite 2 Risk Score at Week 24		Baseline to 24 weeks
Change in PAH-SYMPACT™ from baseline to Week 24		Baseline to 24 weeks
Change in Euro-QoL - 5 Dimensions - 5 Levels (EQ-5D-5L) from baseline to Week 24		Baseline to 24 weeks
Incidence of treatment-emergent adverse events (TEAEs), serious TEAEs (SAEs), and treatment-emergent adverse events of special interest (AESIs)		Baseline to 52 weeks
Proportion of subjects with each of the Clinical Worsening Outcomes:	Death (all causes); Hospitalization for signs and symptoms of worsening PAH (≥ 24 hours); Worsening-related listing for or receipt of lung and/or heart/lung transplantation; Atrial septostomy performed; Worsening PAH requiring initiation of therapy with an additional approved background PAH disease-specific medication or the need to increase the dose of parenteral (IV or subcutaneous infusion) prostacyclin by 10% or more; Disease progression, defined by both of the following events occurring at any time, even if they began at different times, as compared to their baseline values:Decrease in 6MWD of ≥ 15% on two consecutive tests, performed a minimum of 4 hours but no more than 1 week apart ANDWorsened WHO FC	Baseline to 52 weeks
Proportion of subjects who improve from baseline in WHO FC or maintain WHO FC II		Baseline to 24 weeks

Collaborators and Investigators

• Sponsor: GB002, Inc.
• Investigators: Study Director: Richard Aranda, MD, Gossamer Bio Inc.

Publications and helpful links

General Publications

• Sitbon O, Sahay S, Escribano Subias P, Zolty RL, Kingrey JF, Ryan JJ, Sobol I, Sood N, Benza RL, Channick RN, Chin KM, Frantz RP, Ghofrani HA, Hemnes AR, McLaughlin VV, Vachiery JL, Zamanian RT, Ter Veer A, Roscigno RF, Mottola D, Parsley E, Aranda R, Zisman LS, Howard LS; TORREY Study Investigators. Seralutinib for the Treatment of Pulmonary Arterial Hypertension in Adults: TORREY Open-Label Extension Study. Adv Ther. 2025 Oct;42(10):5104-5123. doi: 10.1007/s12325-025-03297-2. Epub 2025 Aug 11.

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2023
• Primary Completion (Actual): November 27, 2025
• Study Completion (Actual): December 22, 2025

Study Registration Dates

• First Submitted: June 28, 2023
• First Submitted That Met QC Criteria: June 28, 2023
• First Posted (Actual): July 7, 2023

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: seralutinib; GB002; PROSERA
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Pulmonary Arterial Hypertension
• Other Study ID Numbers: GB002-3101; 2023-503614-80-00 (Other Identifier: EU-CT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes