GB002 in Adult Subjects With Pulmonary Arterial Hypertension (PAH)

Pulmonary Artery Hypertension Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04456998
• Other study ID #: GB002-2101
• Status: Completed
• Phase: Phase 2
• Start date: November 12, 2020
• Est. completion date: November 1, 2022

Study information

• Verified date: October 2023
• Source: Gossamer Bio Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: November 1, 2022
• Est. primary completion date: October 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypertension
• Pulmonary Arterial Hypertension
• Pulmonary Artery Hypertension

Intervention

Drug:
• GB002 (seralutinib)
Capsule containing GB002 (seralutinib)
• Placebo
Matching capsule containing placebo

Device:
• Generic Dry Powder Inhaler
Generic dry powder inhaler for GB002 (seralutinib) or placebo delivery

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
GB002, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czechia,  France,  Germany,  Serbia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Week 24 in Pulmonary Vascular Resistance (PVR)	PVR was evaluated using right heart catheterization (RHC).	Baseline, Week 24
Secondary	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