GB002 for Pulmonary Arterial Hypertension

Not currently recruiting at 40 trial locations

Overseen By GB002, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 2

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

Must be taking: PAH therapies

Must not be taking: Inhaled prostanoids, Anticoagulants

Disqualifiers: Hypertension, Heart disease, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the long-term effects of a medication called GB002 (seralutinib) for individuals with pulmonary arterial hypertension (PAH), a condition that causes high blood pressure in the lungs. Participants will inhale GB002 twice daily. The trial specifically includes those who have completed a previous GB002 study and have been following their regular PAH treatments. The researchers aim to evaluate the effectiveness and safety of GB002 over time. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that participants continue their standard PAH (Pulmonary Arterial Hypertension) medications at a stable dose. However, you cannot use inhaled prostanoids or chronic oral anticoagulants like warfarin. If you are on these, you may need to stop them to participate.

Is there any evidence suggesting that GB002 (seralutinib) is likely to be safe for humans?

Research has shown that seralutinib, the treatment under study, is safe for patients with pulmonary arterial hypertension (PAH). Studies have found that patients generally tolerate seralutinib well when inhaled twice daily. In earlier research, patients experienced significant improvements in heart pressure and reduced levels of the heart stress marker NT-proBNP, all without major safety concerns. Long-term data also support seralutinib's safety, with consistent findings across multiple studies. This suggests that seralutinib may be a safe option for those considering joining the clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pulmonary arterial hypertension, which often include oral medications like endothelin receptor antagonists, phosphodiesterase-5 inhibitors, or prostacyclin analogs, GB002 (seralutinib) is administered as an inhaled therapy. This delivery method targets the lungs directly, potentially allowing for more effective treatment with fewer systemic side effects. Researchers are particularly excited because seralutinib works by inhibiting PDGFR (platelet-derived growth factor receptor) signaling, which is a novel approach in managing this condition. By targeting the root cause of pulmonary arterial hypertension at the cellular level, GB002 offers a new avenue that could improve outcomes for patients.

What evidence suggests that GB002 (seralutinib) might be an effective treatment for pulmonary arterial hypertension?

Research has shown that seralutinib (GB002), the investigational treatment in this trial, might help treat pulmonary arterial hypertension (PAH). One study found that it significantly lowered pressure in the right side of the heart, reducing stress on the heart. Another study demonstrated improved blood flow in the lungs for those taking seralutinib. Participants also had lower levels of NT-proBNP, a protein linked to heart problems, indicating less strain on the heart. Overall, these findings suggest seralutinib could improve heart and lung function in people with PAH. ^{1 2 3 4 6}

Who Is on the Research Team?

Richard Aranda

Principal Investigator

Gossamer Bio Inc.

Are You a Good Fit for This Trial?

This trial is for adults who've completed a previous GB002 study for Pulmonary Arterial Hypertension (PAH) and were compliant. They must be on stable PAH medications, not have life-threatening heart issues, severe hypertension or hypotension, new left-sided heart disease, substance abuse problems, certain blood disorders or infections. They can't use inhaled tobacco/marijuana but may use ingestible/topical marijuana.

Inclusion Criteria

Subjects must have completed a prior GB002 PAH study and, in the opinion of the Investigator and Sponsor, have been compliant with study procedures and have completed treatment with IP through parent study end-of-treatment (EOT) visit.

I am on a stable dose of standard treatment for PAH.

Review and signature of an IRB-approved informed consent form.

Exclusion Criteria

I have long-term kidney problems.

Your body has very low levels of a type of white blood cells called neutrophils.

I have high blood pressure in my lungs or liver due to cirrhosis, and it's at least moderate in severity.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Extension

Participants continue receiving GB002 (seralutinib) inhaled orally twice per day for long-term evaluation

Up to 80 months or until availability of commercial product

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GB002 (seralutinib)

Trial Overview The trial tests the long-term effects of an inhaler drug called GB002 (seralutinib) in patients with PAH who participated in earlier GB002 studies. It's an open-label extension which means everyone knows they're getting the actual drug and there's no placebo.

How Is the Trial Designed?

Group I: GB002 (seralutinib) Experimental Treatment 2 Interventions

GB002 (seralutinib) inhaled orally twice per day (BID)

GB002 (seralutinib) is already approved in European Union, United States for the following indications:

Approved in European Union as Seralutinib for:

• Pulmonary arterial hypertension (PAH)

Approved in United States as Seralutinib for:

• Pulmonary arterial hypertension (PAH)

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

4

Recruited

260+

Published Research Related to This Trial

Inhaled seralutinib effectively inhibited key receptors involved in pulmonary arterial hypertension (PAH) and demonstrated significant improvements in heart and lung function in two rat models of PAH, outperforming the proof-of-concept drug imatinib.

The treatment with seralutinib led to reduced pulmonary artery muscularization and right ventricle hypertrophy, along with restoration of beneficial protein levels, indicating its potential as a promising therapy for severe PAH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled seralutinib exhibits potent efficacy in models of pulmonary arterial hypertension. Galkin, A., Sitapara, R., Clemons, B., et al.[2023]

In the PATENT-2 study involving 396 patients with pulmonary arterial hypertension, riociguat treatment for over 2 years was well tolerated, with serious adverse events occurring in 60% of patients but only 11% discontinuing due to these events.

Key efficacy parameters such as 6-minute walking distance (6MWD), WHO functional class, and NT-proBNP concentrations were significantly associated with overall survival, highlighting their importance in assessing long-term outcomes in patients receiving riociguat.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Ghofrani, HA., Grimminger, F., Grünig, E., et al.[2022]

In a 1-year study of patients with pulmonary arterial hypertension (PAH), sitaxsentan at 100 mg showed a high overall survival rate of 96% and a lower risk of clinical worsening events (34%) compared to bosentan, which had an 88% survival rate and a 40% risk of worsening.

Sitaxsentan also demonstrated a lower incidence of elevated liver enzymes (6% risk for AST/ALT > 3 x ULN) and discontinuation due to adverse events (15%) compared to bosentan, which had a 14% risk for elevated liver enzymes and a 30% risk of discontinuation due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sitaxsentan for the treatment of pulmonary arterial hypertension: a 1-year, prospective, open-label observation of outcome and survival. Benza, RL., Barst, RJ., Galie, N., et al.[2021]

In a randomized controlled trial involving 120 patients with pulmonary arterial hypertension (PAH) due to left heart disease, the combination of sacubitril/valsartan and dapagliflozin significantly improved heart function and exercise tolerance compared to sacubitril/valsartan alone after 6 months of treatment.

The combination therapy also led to greater reductions in pulmonary artery pressures and inflammatory markers, with no significant increase in adverse drug reactions, indicating that this treatment regimen is both effective and safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A study of the efficacy of sacubitril/valsartan plus dapagliflozin combination treatment in pulmonary arterial hypertension due to left heart disease. Ge, T., Yang, Y., Zhao, Y.[2023]

Seralutinib is a novel inhaled drug targeting PDGFRα/β, CSF1R, and c-KIT pathways, which are implicated in the progression of pulmonary arterial hypertension, and is currently being tested in an ongoing Phase 2 trial with 80 participants.

The primary goal of the trial is to assess changes in pulmonary vascular resistance after 24 weeks of treatment, while secondary outcomes include improvements in exercise capacity measured by the 6-minute walk test.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TORREY, a Phase 2 study to evaluate the efficacy and safety of inhaled seralutinib for the treatment of pulmonary arterial hypertension. Frantz, RP., Benza, RL., Channick, RN., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40788460/

Seralutinib for the Treatment of Pulmonary Arterial ... We present results (as of December 5, 2024) from an open-label extension (OLE) study evaluating long-term safety, tolerability, and efficacy of ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04456998

GB002 in Adult Subjects With Pulmonary Arterial ... The primary objective for this trial is to determine the effect of GB002 (seralutinib) on improving pulmonary hemodynamics in subjects with World Health ...

3. thelancet.com thelancet.com/journals/lanres/article/PIIS2213-2600(24)00072-9/abstract

Seralutinib in adults with pulmonary arterial hypertension ... We aimed to evaluate the efficacy and safety of seralutinib in patients with PAH receiving standard background therapy. Methods. The TORREY ...

4. gossamerbio.com gossamerbio.com/wp-content/uploads/2024/08/Poster-233.pdf

Phase 2 Clinical Study to Evaluate the Efficacy and Safety ... Seralutinib treatment led to significant reduction in right ventricular systolic pressure, data shown as mean ± SEM (A), reduced circulating levels of NT-proBNP ...

5. dzl.de dzl.de/en/news/new-hope-for-pulmonary-arterial-hypertension-seralutinib-shows-promising-results/

New Hope for PAH: Seralutinib Shows Promising Results Promising Results for Seralutinib in Pulmonary Arterial Hypertension** A recent international study shows that the new drug Seralutinib ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2213260024000729

Seralutinib in adults with pulmonary arterial hypertension ... Treatment with inhaled seralutinib significantly decreased PVR, meeting the primary endpoint of the study among patients receiving background therapy for PAH.