Clinical trial NCT04456998: GB002 in Adult Subjects With Pulmonary Arterial Hypertension (PAH)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Artery Hypertension
Keywords: seralutinib
Lead sponsor: Gossamer Bio Inc.
Sponsor class: INDUSTRY
First posted: 2020-07-07
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline to Week 24 in Pulmonary Vascular Resistance (PVR)
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change From Baseline to Week 24 in Distance Achieved on the Six-Minute Walk Test (6MWT)
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pulmonary Associates, PA
state: Arizona
city: Los Angeles
country: United States
facility: Dept of Veterans Affairs Greater Los Angeles Healthcare System
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Francisco
country: United States
facility: The University of California San Francisco
state: California
city: Santa Barbara
country: United States
facility: Medical Corporation
state: California
city: Stanford
country: United States
facility: Stanford Healthcare
state: California
city: Torrance
country: United States
facility: The Lundquist Institute of Biomedical Innovation at Harbor-UCLA Medical Center
state: California
city: Altamonte Springs
country: United States
facility: Central Florida Pulmonary Group, PA
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: The Emory Clinic
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: Kentuckiana Pulmonary Research Center
state: Kentucky
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Albuquerque
country: United States
facility: University of New Mexico Health Sciences Center
state: New Mexico
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital - Weill Cornell Medicine
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: INTEGRIS Baptist Medical Center, Inc.
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Perelman Center for Advanced Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
city: Milwaukee
country: United States
facility: Medical College of Wisconsin - Froedtert Hospital
state: Wisconsin
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital
state: New South Wales
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
city: Hobart
country: Australia
facility: Royal Hobart Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Graz
country: Austria
facility: LKH - Univ. Klinikum Graz - Universitatsklinik fur Innere Medizin
city: Wien
country: Austria
facility: Medizinische Universitat Wien - Universitatsklinik fur Innere Medizin II
city: Bruxelles
country: Belgium
facility: Erasme University Hospital
city: Leuven
country: Belgium
facility: University Hospital of Leuven
city: Montréal
country: Canada
facility: Sir Mortimer B Davis Jewish General Hospital
state: Quebec
city: Calgary
country: Canada
facility: Peter Lougheed Centre
city: London
country: Canada
facility: London Health Sciences Centre - Victoria Hospital
city: Praha
country: Czechia
facility: Všeobecná fakultní nemocnice v Praze
city: Le Kremlin-Bicetre
country: France
facility: AP-HP, Hopital de Bicetre
city: Montpellier
country: France
facility: CHU de Montpellier - Hopital Arnaud de Villeneuve
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum NRW
city: Berlin
country: Germany
facility: DRK Kliniken Berlin - Westend
city: Gießen
country: Germany
facility: Universitätsklinikum Giessen / Marburg
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Zentrum fur Pulmonale Hypertonie Thoraxklinik-Heidelberg gGmbH
city: Regensburg
country: Germany
facility: Universitatsklinikum Regensburg
city: Belgrade
country: Serbia
facility: University Clinical Centre of Serbia
city: Sremska Kamenica
country: Serbia
facility: Institute for Pulmonary Diseases of Vojvodina
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital NHS Foundation
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust - Hammersmith Medicines Research Limited
Study officials:
affiliation: Gossamer Bio Inc.
name: Richard Aranda
role: STUDY_DIRECTOR
References: