Seralutinib for Pulmonary Arterial Hypertension
Recruiting in Palo Alto (17 mi)
+189 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: GB002, Inc.
Must be taking: Endothelin antagonists, PDE5 inhibitors
Must not be taking: Tyrosine kinase inhibitors, Anticoagulants
Disqualifiers: HIV, Hepatitis, Hypertension, others
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
This trial is testing a medication called seralutinib to see if it can help people with a specific type of lung disease (PAH) improve their ability to exercise. The medication works by blocking signals that cause the blood vessels in the lungs to tighten and narrow. Seralutinib is delivered via inhalation and is being developed for patients with pulmonary arterial hypertension. The goal is to see if this can reduce lung pressure and delay worsening of the disease.
Will I have to stop taking my current medications?
The trial requires that participants are on a stable dose of their current PAH medications for at least 12 weeks before and during the screening period. If you are taking certain medications like tyrosine kinase inhibitors or activin signaling inhibitors, you may need to stop them before joining the trial.
What data supports the effectiveness of the drug Seralutinib for pulmonary arterial hypertension?
Research shows that Seralutinib targets specific pathways involved in pulmonary arterial hypertension, potentially reversing harmful changes in the blood vessels of the lungs. Preclinical studies have demonstrated its effectiveness in models of this condition, and it is currently being tested in a Phase 2 clinical trial to further evaluate its impact on patients.12345
Is seralutinib safe for humans?
Seralutinib, also known as GB002, is being tested in a Phase 2 clinical trial for pulmonary arterial hypertension to evaluate its safety and effectiveness. This trial involves 80 participants and includes a 24-week study period followed by an optional 72-week extension, focusing on safety and changes in heart and lung function.12678
What makes the drug Seralutinib unique for treating pulmonary arterial hypertension?
Research Team
RA
Richard Aranda, MD
Principal Investigator
Gossamer Bio Inc.
Eligibility Criteria
Adults aged 18-75 with Pulmonary Arterial Hypertension (PAH) who can walk between 150 and 450 meters in a six-minute test. They must have been on stable PAH medication for at least three months, have specific heart catheterization results, and not be pregnant or nursing. Participants need to use effective contraception if of childbearing potential.Inclusion Criteria
Your heart and lung pressures are higher than normal at rest.
You need to have had a lung function test within the last 12 weeks or have one during the screening.
I am between 18 and 75 years old.
See 10 more
Exclusion Criteria
I have needed strong heart or fluid medication through an IV for more than a day in the last month.
Your blood pressure is too high and not well controlled.
You have a severe medical condition that could make participating in the study risky, such as a history of repeated fainting or bleeding inside the skull.
See 26 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either Seralutinib or placebo inhaled orally twice daily for up to 48 weeks
48 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- Seralutinib (Kinase Inhibitor)
Trial OverviewThe trial is testing Seralutinib's effectiveness in improving exercise capacity for those with WHO Group 1 PAH who are classified as Functional Class II or III. It involves comparing Seralutinib against a placebo using a generic dry powder inhaler to see which is better at preventing clinical worsening.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Seralutinib 90 mgExperimental Treatment2 Interventions
Seralutinib inhaled orally BID up to 48 weeks
Group II: PlaceboPlacebo Group2 Interventions
Placebo inhaled orally twice daily (BID) up to 48 weeks
Seralutinib is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Seralutinib for:
- Pulmonary arterial hypertension (PAH) - Orphan designation
🇺🇸 Approved in United States as Seralutinib for:
- Pulmonary arterial hypertension (PAH) - Orphan designation
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Northwestern Memorial Hospital, Clinical Research UnitChicago, IL
Massachusetts General HospitalBoston, MA
Emory UniversityAtlanta, GA
Norton HospitalLouisville, KY
More Trial Locations
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Who Is Running the Clinical Trial?
GB002, Inc.
Lead Sponsor
Trials
2
Patients Recruited
650+
References
TORREY, a Phase 2 study to evaluate the efficacy and safety of inhaled seralutinib for the treatment of pulmonary arterial hypertension. [2021]Aberrant kinase signaling that involves platelet-derived growth factor receptor (PDGFR) α/β, colony stimulating factor 1 receptor (CSF1R), and stem cell factor receptor (c-KIT) pathways may be responsible for vascular remodeling in pulmonary arterial hypertension. Targeting these specific pathways may potentially reverse the pathological inflammation, cellular proliferation, and fibrosis associated with pulmonary arterial hypertension progression. Seralutinib (formerly known as GB002) is a novel, potent, clinical stage inhibitor of PDGFRα/β, CSF1R, and c-KIT delivered via inhalation that is being developed for patients with pulmonary arterial hypertension. Here, we report on an ongoing Phase 2 randomized, double-blind, placebo-controlled trial (NCT04456998) evaluating the efficacy and safety of seralutinib in subjects with World Health Organization Group 1 Pulmonary Hypertension who are classified as Functional Class II or III. A total of 80 subjects will be enrolled and randomized to receive either study drug or placebo for 24 weeks followed by an optional 72-week open-label extension study. The primary endpoint is the change from baseline to Week 24 in pulmonary vascular resistance by right heart catheterization. The secondary endpoint is the change in distance from baseline to Week 24 achieved in the 6-min walk test. A computerized tomography sub-study will examine the effect of seralutinib on pulmonary vascular remodelling. A separate heart rate monitoring sub-study will examine the effect of seralutinib on cardiac effort during the 6-min walk test.
Inhaled seralutinib exhibits potent efficacy in models of pulmonary arterial hypertension. [2023]Signalling through platelet-derived growth factor receptor (PDGFR), colony-stimulating factor 1 receptor (CSF1R) and mast/stem cell growth factor receptor kit (c-KIT) plays a critical role in pulmonary arterial hypertension (PAH). We examined the preclinical efficacy of inhaled seralutinib, a unique small-molecule PDGFR/CSF1R/c-KIT kinase inhibitor in clinical development for PAH, in comparison to a proof-of-concept kinase inhibitor, imatinib.
Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study. [2022]By its inhibitory effect on platelet-derived growth factor signaling, imatinib could be efficacious in treating patients with pulmonary arterial hypertension (PAH).
[Repeated partially reversible pulmonary arterial hypertension related to dasatinib: a case report and literature review]. [2018]To study the clinical features and prognosis of pulmonary arterial hypertension related to dasatinib.
Pharmacology and Rationale for Seralutinib in the Treatment of Pulmonary Arterial Hypertension. [2023]Pulmonary arterial hypertension (PAH) is a complex disorder characterized by vascular remodeling and a consequent increase in pulmonary vascular resistance. The histologic hallmarks of PAH include plexiform and neointimal lesions of the pulmonary arterioles, which are composed of dysregulated, apoptosis-resistant endothelial cells and myofibroblasts. Platelet-derived growth factor receptors (PDGFR) α and β, colony stimulating factor 1 receptor (CSF1R), and mast/stem cell growth factor receptor kit (c-KIT) are closely related kinases that have been implicated in PAH progression. In addition, emerging data indicate significant crosstalk between PDGF signaling and the bone morphogenetic protein receptor type 2 (BMPR2)/transforming growth factor β (TGFβ) receptor axis. This review will discuss the importance of the PDGFR-CSF1R-c-KIT signaling network in PAH pathogenesis, present evidence that the inhibition of all three nodes in this kinase network is a potential therapeutic approach for PAH, and highlight the therapeutic potential of seralutinib, currently in development for PAH, which targets these pathways.
Predictors of long-term outcomes in patients treated with riociguat for pulmonary arterial hypertension: data from the PATENT-2 open-label, randomised, long-term extension trial. [2022]Pulmonary arterial hypertension is a chronic disease associated with poor long-term outcomes. Identifying predictors of long-term outcome in pulmonary arterial hypertension is important to assess disease severity and guide treatment. We investigate associations between efficacy parameters and long-term outcomes in patients with pulmonary arterial hypertension receiving riociguat in the PATENT-2 study. We also present safety and efficacy data from the final data cutoff of PATENT-2, where most patients had received at least 2 years of riociguat treatment.
Sitaxsentan for the treatment of pulmonary arterial hypertension: a 1-year, prospective, open-label observation of outcome and survival. [2021]Despite advances in the management of pulmonary arterial hypertension (PAH), the mortality rate remains excessive. Long-term efficacy evaluations are needed to guide therapeutic management. The purpose of this study is to present 1-year observational data with two endothelin antagonists, sitaxsentan and bosentan, in a prospective, open-label study.
A Randomized Study of Safety and Efficacy of Two Doses of Ambrisentan to Treat Pulmonary Arterial Hypertension in Pediatric Patients Aged 8 Years up to 18 Years. [2023]To assess the safety and efficacy of the endothelin receptor antagonist ambrisentan in pediatric pulmonary arterial hypertension (PAH).
PK10453, a nonselective platelet-derived growth factor receptor inhibitor, prevents the progression of pulmonary arterial hypertension. [2021]The platelet-derived growth factor (PDGF) signaling pathway has been found to be activated in human pulmonary arterial hypertension (PAH) and in animal models of the disease. Our study tested the hypothesis that a novel, nonselective inhaled PDGF receptor inhibitor, PK10453, would decrease pulmonary hypertension both in the rat monocrotaline (MCT) model and the rat MCT plus pneumonectomy (MCT+PN) model of PAH. PK10453, delivered by inhalation for 4 (D4)- and 8 (D8)-minute exposures 3 times a day for 2 weeks, decreased right ventricular systolic pressure (RVSP) in both the rat MCT and rat MCT+PN models: RVSP was 80.4 ± 2.6 mmHg in the vehicle MCT group (n = 6), 44.4 ± 5.8 mmHg in the D4 MCT group (n = 6), and 37.1 ± 4.5 mmHg in the D8 MCT group (n = 5; P
Update on pharmacotherapy for pulmonary hypertension. [2019]Pulmonary arterial hypertension (PAH) is a rare disease with a poor prognosis if not treated. Pharmacological treatment options for PAH have increased significantly over the past 10 years, with availability of intravenous, oral and inhaled drugs targeting the nitric oxide, endothelin and prostacyclin pathways. Treatment with these therapies in specialised pulmonary hypertension centres has resulted in reductions in patient symptoms, disease progression and mortality, and improved exercise capacity. Recognition of chronic thromboembolic pulmonary hypertension is important, as this cause of pulmonary hypertension may be amenable to surgical treatment. Several new oral drugs, including macitentan, riociguat and selexipag, some of which have novel modes of action, and the use of combinations of PAH drugs have recently been shown to be beneficial in treating PAH and are likely to change treatment for this condition in the future.