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

Pulmonary Arterial Hypertension Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05934526
• Other study ID #: GB002-3101
• Secondary ID: 2023-503614-80-0
• Status: Recruiting
• Phase: Phase 3
• Start date: December 28, 2023
• Est. completion date: October 2025

Study information

• Verified date: April 2024
• Source: Gossamer Bio Inc.
• Contact: GB002, Inc.
• Phone: 1-866-668-4083
• Email: ClinicalTrials[@]gossamerbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: October 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Adult subjects aged 18 to 75 years.

2. Body mass index (BMI) = 17 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 = 450 meters at Screening.

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.

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 24 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) = 12 mmHg if PVR = 400 to < 500 dyne·s/cm^5 OR PCWP or LVEDP = 15 mmHg if PVR = 500 dyne·s/cm^5.

8. Treatment with at least one allowed background PAH disease-specific medication prior to Screening, and on stable regimen and doses for at least 12 weeks.

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 sitting systolic blood pressure > 160 mm Hg or sitting 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 venous-occlusive disease (POVD).

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.

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) > 2 x upper limit of normal (ULN) or total bilirubin = 2 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 < 40 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. Tyrosine kinase inhibitors within 12 weeks 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. 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.

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 8 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.

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Placebo
Matching capsule containing placebo
• Seralutinib
Capsule containing seralutinib

Device:
• Generic Dry Powder Inhaler
Generic dry powder inhaler for seralutinib or placebo delivery

Locations

Country	Name	City	State
Argentina	Cardiologia Palermo	Buenos Aires
Argentina	Instituto Cardiovascular de Buenos Aires	Buenos Aires
Argentina	Hospital Privado Centro Medico de Cordóba S.A.	Córdoba
Argentina	Instituto de Cardiologia de Corrientes Juana Francisca Cabral	Corrientes
Argentina	Instituto de Investigaciones Clinicas Quilmes	Quilmes
Argentina	Instituto Medico Rio Cuarto	Río Cuarto
Argentina	Sanatorio Parque S.A.	Rosario
Australia	Nepean Hospital	Kingswood
Australia	St Vincent's Hospital	Melbourne	Victoria
Australia	Macquarie University	North Ryde	New South Wales
Austria	Religious Hospital Linz GmbH	Linz
Belgium	Hôpital Erasme	Anderlecht
Belgium	University Hospitals of Leuven (Campus Gasthuisberg)	Leuven
Chile	Centro de Investigacion Clinica UC-CICUC	Santiago
Chile	Enroll SpA	Santiago	Region Metropolitana
Czechia	Institut Klinicke a Experimentalni Mediciny	Praha
Czechia	Všeobecná fakultní nemocnice v Praze Il. interní klinika kardiologie a angiologie VFN a 1.LF UK Centrum pro plicní hypertenzi	Praha
Denmark	Aarhus Universitetshospital, Department of Cardiology	Aarhus
Denmark	Rigshospitalet, Department of Cardiology	Copenhagen
France	CHU Bicêtre	Le Kremlin-Bicêtre
France	Institut Coeur Poumon	Lille
France	CHU de Montpellier	Montpellier
France	Hôpital Pasteur	Nice
France	CHU de Poitiers	Poitiers
France	Centre Hospitalier Universitaire - Hôpital d´Adultes de Brabois	Vandœuvre-lès-Nancy
Germany	DRK Kliniken Berlin Westend	Berlin
Germany	Universitatsklinikum Giessen und Marburg GmbH Zentrum fur Innere Medizin, Med. Klinik und Poliklinik II Studienambulanz fur Pulmonale Hypertonie	Gießen
Germany	Universitätsklinikum Halle (Saale) / Martin-Luther-Universität Halle- Wittenberg, Universitätsklinik und Poliklinik für Innere Medizin I	Halle
Germany	Universitätsklinikum Hamburg-Eppendorf Zentrum für Onkologie Studienzentrum Pneumologie	Hamburg
Germany	Medizinische Hochschule Hannover Klinik für Pneumologie und Infektiologie	Hannover
Germany	Thoraxklinik Heidelberg gGmbH am Universitätsklinikum Heidelberg Zentrum für pulmonale Hypertonie	Heidelberg
Germany	Klinikum Wurzburg Mitte gGmbH Medizinische Klinik mit Schwerpunkt Pneumologie und Beatmungsmedizin	Würzburg
Greece	ATTIKON University Hospital, 2nd Critical Care Department	Athens
Greece	Onassis Cardiac Surgery Center	Kallithéa
Greece	AHEPA University General Hospital of Thessaloniki, 1st Cardiology Clinic	Thessaloníki
Israel	Lady Davis Carmel Medical Center	Haifa
Israel	Meir Medical Center	Kfar Saba
Israel	Rabin Medical Center	Petach Tikva
Israel	The Chaim Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	IRCCS Ospedale Policlinico San Martino - Cardiovascular Diseases Unit - Cardiac, Thoracic and Vascular Department	Genova
Italy	Azienda Ospedaliera Dei Colli - Ospedale Monaldi Centro per la Diagnosi e Terapia dell'Ipertensione Polmonare	Napoli
Italy	Azienda Ospealiero Universitaria Policlinico Umberto I - Dipartamento di Scienze Cliniche Internistiche Anestesiologiche e Cardiovascolari - VIII Padglione	Rome
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System Seoul	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary´s Hospital	Seoul
Latvia	Pauls Stradins Clinical University Hospital	Riga
Lithuania	Hospital of Lithuanian University of Health Sciences Kauno klinikos	Kaunas
Netherlands	Amsterdam UMC, location VUmc	Amsterdam
Netherlands	Erasmus MC	Rotterdam
Poland	Krakowski Szpital Specjalistyczny Im. Sw. Jana Pawla II Oddzial Kliniczny Chorób Serca i Naczyn z Pododdzialem Intensywnego Nadzoru Kardiologicznego	Kraków
Poland	Europejskie Centrum Zdrowia Otwock Sp. z o.o. Szpital irn. Fryderyka Chopina Oddzial Kardiologiczny	Otwock
Portugal	Centro Hospitalar e Universitário de Coimbra	Coimbra
Portugal	Centro Hospitalar Universitário Lisboa Norte, EPE - Hospital Pulido Valente	Lisboa
Portugal	Centro Hospitalar Vila Nova De Gaia	Vila Nova De Gaia
Puerto Rico	CardioPulmonary Research Center	Guaynabo
Romania	Emergency Institute of Cardiovascular Diseases "Prof. Dr. C.C. Iliescu" Bucharest, Cardiology 2	Bucharest
Romania	"Niculae Stanciolu" Emergency Heart Institute for Cardivascular Diseases	Cluj-Napoca
Romania	Mediprax Centrum S.R.L	Cluj-Napoca
Romania	Targu-Mures Emergency Clinical County Hospital, Internal Medicine II	Târgu-Mures
Serbia	Institute for Cardiovascular Diseases "Dedinje" Clinic for Cardiology	Belgrade
Serbia	University Clinical Centre of Serbia, Cardiology Clinic	Belgrade
Singapore	National Heart Centre Singapore	Singapore
Singapore	National University Heart Centre Singapore	Singapore
Spain	Hospital Clinic I Provincial	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario 12 De Octubre	Madrid
Spain	Hospital Universitario Puerta De Hierro Majadahonda	Majadahonda
Spain	Hospital Costa del Sol	Marbella
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Universitario Virgen del Rocío	Sevilla
United Kingdom	Golden Jubilee National Hospital, Agamemnon Street	Clydebank
United Kingdom	Hammersmith Hospital	London
United Kingdom	Royal Brompton Hospital, Pulmonary Hypertension Service, Sydney Street	London
United States	University of New Mexico Health Sciences Center	Albuquerque	New Mexico
United States	University of Michigan	Ann Arbor	Michigan
United States	Piedmont Physicians Pulmonary & Sleep Medicine of Buckhead	Atlanta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Medical University of South Carolina - Nexus Research Center	Charleston	South Carolina
United States	Northwestern Memorial Hospital, Clinical Research Unit	Chicago	Illinois
United States	UI Health Hospital	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	University of Missouri	Columbia	Missouri
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Duke University Medical Center - Duke South	Durham	North Carolina
United States	UConn Health/Clinical Research Center	Farmington	Connecticut
United States	CHI St. Luke's Health Baylor College of Medicine Medical Center	Houston	Texas
United States	Houston Methodist Outpatient Center	Houston	Texas
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Dept of Veterans Affairs Greater Los Angeles Healthcare System	Los Angeles	California
United States	Keck Medical Center of USC	Los Angeles	California
United States	Norton Hospital	Louisville	Kentucky
United States	Froedtert Hospital/Medical College of Wisconsin	Milwaukee	Wisconsin
United States	M Health Fairview University of Minnesota Medical Center - East Bank	Minneapolis	Minnesota
United States	INTEGRIS Cardiovascular Physicians, LLC	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	University of California, Irvine Medical Center	Orange	California
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Pulmonary Associates of Richmond, Inc.	Richmond	Virginia
United States	University of Rochester Medical Center	Rochester	New York
United States	UC Davis Health	Sacramento	California
United States	Medical Corporation	Santa Barbara	California
United States	The George Washington University Medical Faculty Associates	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
GB002, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Chile,  Czechia,  Denmark,  France,  Germany,  Greece,  Israel,  Italy,  Korea, Republic of,  Latvia,  Lithuania,  Netherlands,  Poland,  Portugal,  Puerto Rico,  Romania,  Serbia,  Singapore,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in distance achieved on the six-minute walk test (6MWT), six-minute walk distance (?6MWD) from baseline to Week 24		Baseline to 24 weeks
Secondary	Time to first event of Clinical Worsening from first dose of Investigational Product (IP) through end of study		Baseline to 48 weeks
Secondary	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
Secondary	Change in NT-proBNP from baseline to Week 24		Baseline to 24 weeks
Secondary	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
Secondary	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; 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 due to worsening PAH; 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 AND; Worsened WHO FC	Baseline to 52 weeks
Secondary	Proportion of subjects who improve from baseline in WHO FC or maintain WHO FC II		Baseline to 48 weeks
Secondary	Change in PAH-SYMPACT™ from baseline to Week 24		Baseline to 24 weeks
Secondary	Change in Euro-QoL - 5 Dimensions - 5 Levels (EQ-5D-5L) from baseline to Week 24		Baseline to 24 weeks
Secondary	Incidence of treatment-emergent adverse events (TEAEs), serious TEAEs (SAEs), and treatment-emergent adverse events of special interest (AESIs)		Baseline to 52 weeks