GB002 in Adult Subjects With Pulmonary Arterial Hypertension (PAH)

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Clinical Study to Evaluate the Efficacy and Safety of Oral Inhalation of GB002 for the Treatment of WHO Group 1 Pulmonary Arterial Hypertension (PAH)

The primary objective for this trial is to determine the effect of GB002 (seralutinib) on improving pulmonary hemodynamics in subjects with World Health Organization (WHO) Group 1 PAH who are Functional Class (FC) II and III. The secondary objective for this trial is to determine the effect of GB002 (seralutinib) on improving exercise capacity in this population.

Study Overview

• Status: Completed
• Conditions: Pulmonary Artery Hypertension
• Intervention / Treatment: Drug: GB002 (seralutinib); Device: Generic Dry Powder Inhaler; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Fitzroy, Australia, 3065
    • St Vincent's Hospital Melbourne
  • Hobart, Australia, TAS 7000
    • Royal Hobart Hospital
  • Westmead, Australia, NSW 2145
    • Westmead Hospital
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's hospital
• Austria
  • Graz, Austria, 8036
    • LKH - Univ. Klinikum Graz - Universitatsklinik fur Innere Medizin
  • Wien, Austria, 1090
    • Medizinische Universitat Wien - Universitatsklinik fur Innere Medizin II
• Belgium
  • Bruxelles, Belgium, 1070
    • Erasme University Hospital
  • Leuven, Belgium, 3000
    • University Hospital of Leuven
• Canada
  • Calgary, Canada, T1Y 6J4
    • Peter Lougheed Centre
  • London, Canada, N6A 5W9
    • London Health Sciences Centre - Victoria Hospital
  • Quebec
    • Montréal, Quebec, Canada, H3T 1E2
      • Sir Mortimer B Davis Jewish General Hospital
• Czechia
  • Praha, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze
• France
  • Le Kremlin-Bicetre, France, 94270
    • AP-HP, Hopital de Bicetre
  • Montpellier, France, 34295
    • CHU de Montpellier - Hôpital Arnaud de Villeneuve
• Germany
  • Bad Oeynhausen, Germany, 32545
    • Herz- und Diabeteszentrum NRW
  • Berlin, Germany, 14050
    • DRK Kliniken Berlin - Westend
  • Gießen, Germany, 35392
    • Universitätsklinikum Giessen / Marburg
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany, 69126
    • Zentrum fur Pulmonale Hypertonie Thoraxklinik-Heidelberg gGmbH
  • Regensburg, Germany, 93053
    • Universitätsklinikum Regensburg
• Serbia
  • Belgrade, Serbia, 11000
    • University Clinical Centre of Serbia
  • Sremska Kamenica, Serbia, 21204
    • Institute For Pulmonary Diseases of Vojvodina
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebrón
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de octubre
  • Santander, Spain, 39008
    • Hospital Universitario Marqués de Valdecilla
• United Kingdom
  • Cambridge, United Kingdom, CB2 0AY
    • Royal Papworth Hospital NHS Foundation
  • London, United Kingdom, W12 OHS
    • Imperial College Healthcare NHS Trust - Hammersmith Medicines Research Limited
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Pulmonary Associates, PA
  • California
    • Los Angeles, California, United States, 90073
      • Dept of Veterans Affairs Greater Los Angeles Healthcare System
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • San Francisco, California, United States, 94143
      • The University of California San Francisco
    • Santa Barbara, California, United States, 93105
      • Medical Corporation
    • Stanford, California, United States, 94305
      • Stanford Healthcare
    • Torrance, California, United States, 90502
      • The Lundquist Institute of Biomedical Innovation at Harbor-UCLA Medical Center
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Central Florida Pulmonary Group, PA
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic
  • 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
      • Kentuckiana Pulmonary Research Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's 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
      • University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint 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
    • New York, New York, United States, 10065
      • New York Presbyterian Hospital - Weill Cornell Medicine
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
    • Cleveland, Ohio, United States, 44124
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • INTEGRIS Baptist Medical Center, Inc.
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Perelman Center for Advanced Medicine
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin - Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. A current diagnosis of symptomatic PAH classified by one of the following:

   1. Idiopathic PAH (IPAH) or heritable pulmonary arterial hypertension (HPAH).
   2. PAH associated with connective tissue disease (CTD-APAH).
   3. PAH associated with anorexigen or methamphetamine use.
   4. Congenital heart disease with simple systemic to pulmonary shunt at least 1 year after surgical repair.
2. 6MWD ≥ 150 meters and ≤ 550 meters at screening.
3. WHO FC II or III symptomatology.
4. Treatment with standard of care PAH background therapies.

5. Documentation of cardiac catheterization within the screening period that is consistent with the diagnosis of PAH and meeting all the following criteria, to be confirmed by a central hemodynamic core laboratory:

   1. Mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg (at rest), AND
   2. PVR ≥ 400 dyne•sec/cm5, AND
   3. Pulmonary capillary wedge pressure (PCWP) or left ventricular-end diastolic pressure (LVEDP) ≤12 mm Hg if PVR ≥400 to <500 dyne∙sec/cm5 OR
   4. PCWP or LVEDP ≤15 mmHg if PVR ≥500 dyne∙sec/cm5

6. Pulmonary function tests (PFTs) at screening with the following criteria met:

   1. Forced expiratory volume in 1 second (FEV1) divided by the forced vital capacity (FVC) ≥70%;
   2. Total lung capacity (TLC) or FVC ≥ 70% predicted

Exclusion Criteria:

1. Evidence of chronic thromboembolic disease or acute pulmonary embolism as assessed by ventilation-perfusion (V/Q) scan, computed tomography (CT)-angiogram, or pulmonary angiogram prior to screening.
2. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure > 160 mm Hg or sitting diastolic blood pressure > 100 mm Hg during screening visit after a period of rest.
3. Systolic blood pressure < 90 mm Hg during screening and baseline visits.
4. WHO Pulmonary Hypertension Group 2-5.
5. Human immunodeficiency virus (HIV)-associated PAH.
6. History of left-sided heart disease and/or clinically significant cardiac disease.
7. Untreated severe obstructive sleep apnea.
8. History of atrial septostomy within 180 days prior to screening.
9. Pulmonary venous occlusive disease (PVOD).
10. Subjects with a history of portopulmonary hypertension or portal hypertension due to cirrhosis classified as Child-Pugh Class A or higher; or baseline ALT or AST > 2 x ULN or Total Bilirubin ≥ 2 x ULN.
11. History of malignancy within 5 years prior to screening.
12. History of a potentially life-threatening cardiac arrhythmia with an ongoing risk.
13. Severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or IP administration (eg; history intracranial hemorrhage).
14. Chronic renal insufficiency as defined by an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m2 via Chronic Kidney Disease Epidemiology Collaboration (CKD-epi) at screening or requires dialytic therapy or hemofiltration.
15. Hemoglobin (Hgb) concentration < 8.5 g/dL at screening.
16. Evidence of active HIV, Hepatitis B or Hepatitis C, or tuberculosis (TB) infections.
17. Inhaled prostanoids; these drugs may be withdrawn ≥ 4 weeks prior to or at screening, if clinically indicated.
18. Use of oral anticoagulants (ie, warfarin or NOAC) at randomization.
19. Requirement of intravenous (IV) inotropes (ie, levosimendan, dopamine, dobutamine, milrinone, norepinephrine) other than an IV prostanoid within 4 weeks of screening.
20. Prior participation in GB002 studies and/or prior treatment with GB002.
21. 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 4 weeks prior to screening.
22. Current use of inhaled tobacco and/or inhaled marijuana.
23. Current alcohol use disorder as defined by DSM-5 and/or positive test for drugs of abuse (amphetamines, methamphetamines, cocaine, phencyclidine [PCP]).
24. Subjects with a history of severe milk protein allergy. In addition, subjects with known intolerance or hypersensitivity to lactose who, in the opinion of the investigator, may experience severe symptoms following the ingestion of lactose.
25. QTcF of > 480 msec recorded on a screening or baseline ECG or receiving concurrent treatment with medications that prolong QT interval.
26. Have any other condition or reason that, in the opinion of the Investigator or Medical Monitor, would prohibit the subject from participating in the study.

NOTE: Additional inclusion/exclusion criteria may apply, per protocol.

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
Experimental: GB002 (seralutinib); GB002 (seralutinib) inhaled orally twice per day (BID) for 24 weeks	Drug: GB002 (seralutinib); Capsule containing GB002 (seralutinib); Device: Generic Dry Powder Inhaler; Generic dry powder inhaler for GB002 (seralutinib) or placebo delivery
Placebo Comparator: Placebo; Placebo inhaled orally BID for 24 weeks	Device: Generic Dry Powder Inhaler; Generic dry powder inhaler for GB002 (seralutinib) or placebo delivery; Drug: Placebo; Matching capsule containing placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 24 in Pulmonary Vascular Resistance (PVR)	PVR was evaluated using right heart catheterization (RHC).	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 24 in Distance Achieved on the Six-Minute Walk Test (6MWT)	The 6MWT measures the distance a participant is able to walk quickly on a flat, hard surface in a period of 6 minutes.	Baseline, Week 24

Collaborators and Investigators

• Sponsor: GB002, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
• Investigators: Study Director: Richard Aranda, Gossamer Bio Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2020
• Primary Completion (Actual): October 17, 2022
• Study Completion (Actual): November 1, 2022

Study Registration Dates

• First Submitted: June 30, 2020
• First Submitted That Met QC Criteria: June 30, 2020
• First Posted (Actual): July 7, 2020

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: seralutinib
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension
• Other Study ID Numbers: GB002-2101

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