Seralutinib for Pulmonary Arterial Hypertension

Not currently recruiting at 212 trial locations

Overseen By GB002, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 3

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) This treatment is in the last trial phase before FDA approval

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

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called seralutinib to determine if it can help people with Pulmonary Arterial Hypertension (PAH) improve exercise ability and delay condition worsening. Participants will receive either seralutinib or a placebo (a non-active substance) for comparison. It suits those with PAH who can manage short walks but struggle with longer distances. As a Phase 3 trial, this treatment is in the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in PAH treatment.

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.

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

Research has shown that seralutinib is safe for people with pulmonary arterial hypertension (PAH). Studies indicate that patients using inhaled seralutinib long-term generally tolerate it well. These studies have reported no major safety issues. While some side effects can occur, they are usually mild and manageable. Overall, the evidence supports seralutinib's safety for long-term use in treating PAH. ^{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 and phosphodiesterase-5 inhibitors, Seralutinib is unique because it is inhaled. This delivery method allows the drug to act directly on the lungs, potentially leading to more effective results with fewer systemic side effects. Researchers are excited about Seralutinib because it targets multiple pathways involved in the disease, which could offer new hope for patients who don't respond well to existing therapies.

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

Research has shown that seralutinib might help treat pulmonary arterial hypertension (PAH). In animal studies, seralutinib improved heart and lung function. A study with patients found it reduced pressure in the right side of the heart, indicating less strain on the heart. Another study found it lowered levels of a substance linked to heart failure. These results suggest seralutinib could help manage PAH symptoms and improve exercise ability. Participants in this trial will receive either seralutinib or a placebo to further evaluate its effectiveness. ^{1 3 6 7 8}

Who Is on the Research Team?

Richard Aranda, MD

Principal Investigator

Gossamer Bio Inc.

Are You a Good Fit for This Trial?

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.

My PAH is due to genetics, connective tissue disease, drug use, or heart defect repair.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Seralutinib

Trial Overview The 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.

How Is the Trial Designed?

Group I: Seralutinib 90 mg Experimental Treatment 2 Interventions

Seralutinib inhaled orally BID up to 48 weeks

Group II: Placebo Placebo Group 2 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

Who Is Running the Clinical Trial?

GB002, Inc.

Lead Sponsor

Trials

2

Recruited

650+

Published Research Related to This Trial

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]

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 24-week randomized trial involving 202 patients with pulmonary arterial hypertension (PAH), imatinib significantly improved exercise capacity, as measured by a 32-meter increase in the 6-minute walk distance compared to placebo.

While imatinib showed beneficial effects on exercise and hemodynamics, it was associated with a higher rate of serious adverse events and discontinuations, indicating a need for further research on its long-term safety in PAH patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study. Hoeper, MM., Barst, RJ., Bourge, RC., et al.[2022]

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 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]

The novel inhaled PDGF receptor inhibitor PK10453 significantly reduced right ventricular systolic pressure (RVSP) in rat models of pulmonary arterial hypertension (PAH), demonstrating its efficacy in both the monocrotaline (MCT) and MCT plus pneumonectomy (MCT+PN) models over a 2-week treatment period.

PK10453's nonselective inhibition of both PDGFα and PDGFβ receptors may provide a therapeutic advantage over the selective PDGFα receptor inhibitor imatinib, which was effective only in the MCT model and not in the MCT+PN model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PK10453, a nonselective platelet-derived growth factor receptor inhibitor, prevents the progression of pulmonary arterial hypertension. Medarametla, V., Festin, S., Sugarragchaa, C., et al.[2021]

The PDGFR-CSF1R-c-KIT signaling network plays a crucial role in the progression of pulmonary arterial hypertension (PAH), which is characterized by changes in blood vessel structure and increased resistance in the lungs.

Inhibiting all three components of this signaling network may offer a promising therapeutic strategy for PAH, with seralutinib being a potential treatment currently under development that targets these pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology and Rationale for Seralutinib in the Treatment of Pulmonary Arterial Hypertension. Pullamsetti, SS., Sitapara, R., Osterhout, R., et al.[2023]

In a phase IIb study involving 41 pediatric patients aged 8 to <18 years with pulmonary arterial hypertension (PAH), ambrisentan was found to be well tolerated, with most treatment-emergent adverse events (TEAEs) being mild to moderate in severity, similar to the safety profile observed in adults.

The study showed a significant improvement in the 6-minute walking distance after 24 weeks of treatment, with 70% of patients maintaining or improving their World Health Organization functional class, suggesting that ambrisentan may be effective for treating PAH in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Ivy, D., Beghetti, M., Juaneda-Simian, E., et al.[2023]

Over the past decade, the treatment options for pulmonary arterial hypertension (PAH) have expanded significantly, leading to improved patient outcomes such as reduced symptoms, slowed disease progression, and lower mortality rates.

New oral medications like macitentan, riociguat, and selexipag, along with combination therapies, have shown promise in treating PAH, indicating a shift towards more effective management strategies for this serious condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on pharmacotherapy for pulmonary hypertension. Prior, DL., Adams, H., Williams, TJ.[2019]

Dasatinib, a medication used for chronic myelogenous leukemia, can lead to pulmonary arterial hypertension (PAH), which may be partially reversible upon stopping the drug, as seen in a case study of a 55-year-old male patient.

However, repeated use of dasatinib may result in irreversible PAH, highlighting the importance of monitoring pulmonary arterial pressure during treatment with transthoracic Doppler echocardiography.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Repeated partially reversible pulmonary arterial hypertension related to dasatinib: a case report and literature review]. Jin, J., Xu, XM., Wang, C.[2018]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9724289/

Inhaled seralutinib exhibits potent efficacy in models of ... Inhaled seralutinib was an effective treatment of severe PAH in two animal models, with improved cardiopulmonary haemodynamic parameters, a reduction in NT- ...

3. gossamerbio.com gossamerbio.com/wp-content/uploads/2024/08/Poster-A2907.pdf

Phase 1a Randomized, Double-Blind, Placebo-Controlled, ... Pulmonary arterial hypertension (PAH) is an orphan disease associated with high morbidity and mortality with high unmet medical needs.

4. 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 ...

5. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03473236

Phase 1A Safety Trial of Inhaled PK10571 (GB002) This is a first-in-human, single-center, randomized, double-blind, placebo-controlled, two-part study in healthy adult males and females of non-childbearing ...

7. go.drugbank.com go.drugbank.com/drugs/DB18072

Seralutinib: Uses, Interactions, Mechanism of Action Improve decision support & research outcomes with our structured adverse effects data. ... Pulmonary Arterial Hypertension (PAH) · 1, somestatus ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12474731/

Seralutinib for the Treatment of Pulmonary Arterial ... These OLE data are consistent with TORREY results and support long-term safety and efficacy of inhaled seralutinib in patients with PAH. A phase ...