HS135 for Heart Failure and Pulmonary Hypertension

Recruiting at 2 trial locations

Overseen By Roxanne Julien, M.Sc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: 35Pharma Inc

Disqualifiers: Decompensated heart failure, Uncontrolled hypertension, others

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

4 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of a new treatment called HS135 for individuals with both heart failure and pulmonary hypertension (high blood pressure in the lungs). The treatment involves a subcutaneous injection (an injection under the skin) and will be compared to a placebo (a harmless, inactive shot). The trial seeks participants with heart failure with preserved ejection fraction (a type of heart failure where the heart pumps normally but is still impaired) who have had a heart monitoring device implanted for at least 90 days. Participants should also have a BMI of 30 or higher and experience moderate to severe heart failure symptoms.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that HS135 is likely to be safe for humans?

Research has shown that HS135 is generally well-tolerated, with most people experiencing few side effects. Studies have found that the drug effectively reaches the necessary areas in the body. These results are encouraging for those considering participation in a trial with HS135. However, since this trial is still in its early stages, not all possible side effects may be known. Overall, the initial safety data looks promising, but further research will provide a clearer picture. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for heart failure and pulmonary hypertension, which often include medications like ACE inhibitors, beta-blockers, and diuretics, HS135 is unique because it is administered through a subcutaneous injection. This delivery method could allow for more targeted treatment and potentially fewer side effects. Researchers are excited because HS135 might offer a new mechanism of action that directly impacts the pathways contributing to both heart failure and pulmonary hypertension, potentially improving patient outcomes more effectively and quickly than current options.

What evidence suggests that HS135 might be an effective treatment for PH-HFpEF?

Research has shown that HS135, a new treatment under study in this trial, could help with conditions like high blood pressure in the lungs and heart failure related to obesity. Early studies in lab models indicated that HS135 effectively reduces symptoms of both conditions. This treatment blocks certain proteins linked to these health issues. Patients who used HS135 showed improvements in body composition, suggesting it might help manage symptoms related to obesity. While more research is needed in humans, these initial findings are promising for those with high blood pressure in the lungs and heart failure. Participants in this trial will receive either HS135 or a placebo to further evaluate its effectiveness. ^{1 2 3 6 7}

Who Is on the Research Team?

Monique Champagne, M.Sc.

Principal Investigator

35Pharma Inc

Are You a Good Fit for This Trial?

This trial is for adults over 18 with obesity (BMI ≥ 30 kg/m2), diagnosed heart failure where the heart pumps normally (LVEF at least 45%), and symptoms that affect daily life to varying degrees. They must have a CardioMEMS™ device implanted for monitoring heart failure, be able to follow the study plan, and understand protocol requirements.

Inclusion Criteria

I am over 18 years old.

I have had a CardioMEMS device for heart failure implanted for at least 90 days.

I can follow the study's schedule and understand all its requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HS135 or placebo via subcutaneous injection. Multiple ascending doses are administered to assess pharmacokinetics, safety, pharmacodynamics, and efficacy.

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in clinical laboratory parameters and incidence of adverse events.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HS135

Trial Overview The trial is testing HS135 against a placebo in obese patients who have both pulmonary hypertension—a type of high blood pressure affecting lungs' arteries—and heart failure with normal pumping function. The goal is to see if HS135 can improve their condition.

How Is the Trial Designed?

Group I: Investigational Product Experimental Treatment 1 Intervention

HS135 Subcutaneous Injection

Group II: Placebo Placebo Group 1 Intervention

Subcutaneous Injection

Who Is Running the Clinical Trial?

35Pharma Inc

Lead Sponsor

Trials

3

Recruited

120+

Published Research Related to This Trial

A review of 588 pediatric adverse event reports related to pulmonary hypertension medications revealed significant safety concerns, including 27 adverse events not previously documented in the literature, such as pulmonary hemorrhage and pneumonia.

The findings highlight the need for better communication of postmarket adverse event data from the FDA to healthcare providers, as many medications for pediatric pulmonary hypertension are used off-label and may carry risks that are not well understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Food and Drug Administration (FDA) postmarket reported side effects and adverse events associated with pulmonary hypertension therapy in pediatric patients. Maxey, DM., Ivy, DD., Ogawa, MT., et al.[2021]

In a study of 34 patients with heart failure and pulmonary hypertension, sildenafil significantly improved exercise capacity, as shown by a greater increase in peak VO2 compared to placebo after 12 weeks of treatment.

Sildenafil also reduced pulmonary vascular resistance and improved quality of life, evidenced by a longer 6-minute walk distance and a better Minnesota Living With Heart Failure score, while being generally safe with fewer hospitalizations for heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Lewis, GD., Shah, R., Shahzad, K., et al.[2022]

A meta-analysis of six randomized controlled trials involving 206 patients with pulmonary hypertension secondary to chronic systolic heart failure showed that sildenafil treatment significantly reduced hospital admissions compared to placebo (3.15% vs. 12.20%).

Sildenafil also improved various health metrics, including reduced mean pulmonary artery pressure and pulmonary vascular resistance, increased left ventricular ejection fraction, and enhanced exercise capacity, leading to better quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Additional use of a phosphodiesterase 5 inhibitor in patients with pulmonary hypertension secondary to chronic systolic heart failure: a meta-analysis. Wu, X., Yang, T., Zhou, Q., et al.[2015]

In a study of 58 elderly patients with pulmonary hypertension due to left ventricular heart failure, the Rho kinase inhibitor fasudil significantly improved pulmonary arterial pressure and cardiac function in patients with reactive pulmonary hypertension (RPH) after 2 weeks of treatment.

Fasudil showed a higher total effective rate of 74.29% in the RPH group compared to 47.83% in the passive pulmonary hypertension (PPH) group, suggesting it may be particularly beneficial for patients with RPH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Fasudil on Patients with Pulmonary Hypertension Associated with Left Ventricular Heart Failure with Preserved Ejection Fraction: A Prospective Intervention Study. Zhang, X., Zhang, X., Wang, S., et al.[2019]

In the Sildenafil in Heart Failure (SilHF) trial involving 69 patients with heart failure and pulmonary hypertension, sildenafil did not show any significant improvement in symptoms, quality of life, or exercise capacity compared to placebo.

While sildenafil was generally well tolerated, there was a higher incidence of serious adverse events in the sildenafil group (33%) compared to the placebo group (21%), raising concerns about its safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of sildenafil on symptoms and exercise capacity for heart failure with reduced ejection fraction and pulmonary hypertension (the SilHF study): a randomized placebo-controlled multicentre trial. Cooper, TJ., Cleland, JGF., Guazzi, M., et al.[2022]

In patients with heart failure and reduced left ventricular ejection fraction (HFREF), phosphodiesterase-5 inhibitors (PDE5i) significantly reduced the risk of death and hospitalization, with an odds ratio of 0.28, and improved exercise capacity and pulmonary arterial pressure.

However, in patients with heart failure and preserved left ventricular ejection fraction (HFpEF), PDE5i did not show any significant benefits in clinical outcomes or exercise capacity, indicating that their efficacy may be limited to HFREF patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic benefits of phosphodiesterase-5 inhibition in chronic heart failure: A meta-analysis. Vecchis, R., Cesaro, A., Ariano, C.[2022]

Phosphodiesterase 5 inhibitors, particularly Sildenafil, have been shown to improve hemodynamics, exercise capacity, and quality of life in patients with pulmonary hypertension due to left heart disease, based on a systematic review of five randomized clinical trials.

Sildenafil was well tolerated across all studies, suggesting it is a safe option for treating pulmonary hypertension in this patient population, although further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapy with phosphodiesterase 5 inhibitors in patients with pulmonary hypertension due to heart failure and elevated pulmonary vascular resistance: a systematic review. Sanchez Palacios, GM., Schmidt, C., Wichman, T.[2020]

In a study of 13 patients with systemic sclerosis-associated pulmonary arterial hypertension treated with selexipag, 8 out of 11 patients showed stabilization or improvement in their condition after 12 weeks, indicating the drug's efficacy in this high-risk group.

Selexipag was generally well-tolerated, with only two patients discontinuing treatment due to side effects, suggesting an acceptable safety profile for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selexipag treatment in patients with systemic sclerosis-associated pulmonary arterial hypertension in clinical practice, a case series. Lemmers, JM., Fretheim, H., Knaapen, HK., et al.[2022]

In a study of 66 pediatric patients with pulmonary hypertension on sildenafil, 30% reported experiencing side effects, with the most common being gastrointestinal (37%), vascular (35%), and neurologic (22%).

Patients on combination therapy with sildenafil and other treatments had a higher incidence of side effects compared to those on sildenafil alone, indicating that combining therapies may increase the risk of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reported sildenafil side effects in pediatric pulmonary hypertension patients. Siehr, SL., McCarthy, EK., Ogawa, MT., et al.[2020]

PDE5 inhibitors, such as sildenafil, have been shown to significantly improve heart function and oxygen levels in children with pulmonary hypertension, based on a systematic review of 21 studies including 8 randomized controlled trials.

Low- and moderate-dose sildenafil regimens are considered safe for pediatric patients, but more research is needed to establish the best treatment strategies for managing pulmonary hypertension in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary Hypertension Therapy and a Systematic Review of Efficacy and Safety of PDE-5 Inhibitors. Unegbu, C., Noje, C., Coulson, JD., et al.[2018]

Sildenafil therapy significantly reduces pulmonary arterial systolic pressure and improves pulmonary hemodynamics in patients with pulmonary hypertension due to left heart disease (PH-LHD) and heart failure with reduced ejection fraction (HFrEF), as shown in a meta-analysis of randomized and observational studies.

The treatment not only enhances oxygen consumption and left ventricular ejection fraction over time but also improves the quality of life for patients, indicating its efficacy in managing PH-LHD with HFrEF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of sildenafil for pulmonary hypertension due to left heart disease with HFrEF. Jiang, R., Wang, L., Zhu, CT., et al.[2022]

Citations

1. ahajournals.org ahajournals.org/doi/10.1161/circ.146.suppl_1.10487

Abstract 10487: In vivo Efficacy of HS135, a Novel Activin ... Abstract 10487: In vivo Efficacy of HS135, a Novel Activin and GDF Trap for the Treatment of Pulmonary Hypertension (PH) and Metabolic Syndrome ...

2. atsjournals.org atsjournals.org/doi/abs/10.1164/ajrccm.2025.211.Abstracts.A7052

HS135, a Novel Investigational Activin Inhibitor for the ... Conclusion: HS135 was generally well tolerated and led to high levels of target engagement. The observed improvement in body composition as well as prognostic ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06493461

A Study of HS135 for the Treatment of Pulmonary Arterial ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

4. academic.oup.com academic.oup.com/eurheartj/article/44/Supplement_2/ehad655.3249/7391202

HS135, a novel activin and GDF trap, is highly efficacious in ... HS135, a novel activin and GDF trap, is highly efficacious in preclinical models of pulmonary hypertension and obesity-associated heart failure ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1071916424004494

Phase Ib Study Of Hs135, A Novel Activin And Gdf Inhibitor ... This is a Phase 1b trial in progress to assess the preliminary safety and efficacy of the novel Activin and GDF inhibitor HS135 in obese patients with PH-HFpEF.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06581159

NCT06581159 | Study of HS135 in Obese Patients With ... ... Safety, Pharmacodynamics, and Efficacy of HS135 in Obese Patients with Pulmonary Hypertension and Heart Failure with Preserved Ejection Fraction. Official ...

7. publications.ersnet.org publications.ersnet.org/content/erj/60/suppl66/3238

HS135: Novel Activin & GDF Ligand Trap for the Treatment of ... Abstract · HS135, a novel activin and GDF trap, is highly efficacious in preclinical models of pulmonary hypertension and obesity-associated heart failure with ...