GB002 in Adult Subjects With Pulmonary Arterial Hypertension (PAH)

NCT ID: NCT04456998

Last Updated: 2023-11-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-12
• Study Completion Date: 2022-11-01

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.

Conditions

Pulmonary Artery Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

GB002 (seralutinib)

GB002 (seralutinib) inhaled orally twice per day (BID) for 24 weeks

Group Type: EXPERIMENTAL

GB002 (seralutinib)

Intervention Type: DRUG

Capsule containing GB002 (seralutinib)

Generic Dry Powder Inhaler

Intervention Type: DEVICE

Generic dry powder inhaler for GB002 (seralutinib) or placebo delivery

Placebo

Placebo inhaled orally BID for 24 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching capsule containing placebo

Generic Dry Powder Inhaler

Intervention Type: DEVICE

Generic dry powder inhaler for GB002 (seralutinib) or placebo delivery

Interventions

GB002 (seralutinib)

Capsule containing GB002 (seralutinib)

Intervention Type: DRUG

Placebo

Matching capsule containing placebo

Intervention Type: DRUG

Generic Dry Powder Inhaler

Generic dry powder inhaler for GB002 (seralutinib) or placebo delivery

Intervention Type: DEVICE

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GB002, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Aranda

Role: STUDY_DIRECTOR

Gossamer Bio Inc.

Locations

Pulmonary Associates, PA

Phoenix, Arizona, United States

Dept of Veterans Affairs Greater Los Angeles Healthcare System

Los Angeles, California, United States

UC Davis Medical Center

Sacramento, California, 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

Central Florida Pulmonary Group, PA

Altamonte Springs, Florida, United States

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Cleveland Clinic Florida

Weston, Florida, United States

The Emory Clinic

Atlanta, Georgia, United States

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Kentuckiana Pulmonary Research Center

Louisville, Kentucky, United States

Tufts Medical Center

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, United States

NYU Langone Health

New York, New York, United States

New York Presbyterian Hospital - Weill Cornell Medicine

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, 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

INTEGRIS Baptist Medical Center, Inc.

Oklahoma City, Oklahoma, United States

Oregon Health & Science University

Portland, Oregon, United States

Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

University of Utah Health

Salt Lake City, Utah, United States

Medical College of Wisconsin - Froedtert Hospital

Milwaukee, Wisconsin, United States

St Vincent's Hospital

Darlinghurst, New South Wales, Australia

St Vincent's Hospital Melbourne

Fitzroy, , Australia

Royal Hobart Hospital

Hobart, , Australia

Westmead Hospital

Westmead, , Australia

LKH - Univ. Klinikum Graz - Universitatsklinik fur Innere Medizin

Graz, , Austria

Medizinische Universitat Wien - Universitatsklinik fur Innere Medizin II

Vienna, , Austria

Erasme University Hospital

Brussels, , Belgium

University Hospital of Leuven

Leuven, , Belgium

Sir Mortimer B Davis Jewish General Hospital

Montreal, Quebec, Canada

Peter Lougheed Centre

Calgary, , Canada

London Health Sciences Centre - Victoria Hospital

London, , Canada

Všeobecná fakultní nemocnice v Praze

Prague, , Czechia

AP-HP, Hopital de Bicetre

Le Kremlin-Bicêtre, , France

CHU de Montpellier - Hopital Arnaud de Villeneuve

Montpellier, , France

Herz- und Diabeteszentrum NRW

Bad Oeynhausen, , Germany

DRK Kliniken Berlin - Westend

Berlin, , Germany

Universitätsklinikum Giessen / Marburg

Giessen, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Zentrum fur Pulmonale Hypertonie Thoraxklinik-Heidelberg gGmbH

Heidelberg, , Germany

Universitatsklinikum Regensburg

Regensburg, , Germany

University Clinical Centre of Serbia

Belgrade, , Serbia

Institute for Pulmonary Diseases of Vojvodina

Kamenitz, , Serbia

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario Marqués de Valdecilla

Santander, , Spain

Royal Papworth Hospital NHS Foundation

Cambridge, , United Kingdom

Imperial College Healthcare NHS Trust - Hammersmith Medicines Research Limited

London, , United Kingdom

Countries

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

References

Frantz RP, McLaughlin VV, Sahay S, Escribano Subias P, Zolty RL, Benza RL, Channick RN, Chin KM, Hemnes AR, Howard LS, Sitbon O, Vachiery JL, Zamanian RT, Cravets M, Roscigno RF, Mottola D, Osterhout R, Bruey JM, Elman E, Tompkins CA, Parsley E, Aranda R, Zisman LS, Ghofrani HA; TORREY Study Investigators. Seralutinib in adults with pulmonary arterial hypertension (TORREY): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Respir Med. 2024 Jul;12(7):523-534. doi: 10.1016/S2213-2600(24)00072-9. Epub 2024 May 2.

Reference Type: DERIVED

PMID: 38705167 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GB002-2101

Identifier Type: -

Identifier Source: org_study_id