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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

A Study of HS135 for the Treatment of in Obese Patients with Pulmonary Hypertension and Heart Failure with Preserved Ejection Fraction (PH-HFpEF)

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.

What data supports the effectiveness of the drug HS135 for heart failure and pulmonary hypertension?

Research shows that phosphodiesterase 5 inhibitors, like sildenafil, can improve exercise capacity, quality of life, and reduce pulmonary pressure in patients with heart failure and pulmonary hypertension. These findings suggest that similar treatments may be beneficial for these conditions. ^{1 2 3 4 5}

Is HS135 (sildenafil) safe for use in humans?

Sildenafil, a type of phosphodiesterase 5 inhibitor, has been generally well tolerated in studies for pulmonary hypertension, improving exercise capacity and quality of life. However, in pediatric patients, there have been reports of serious side effects, including some not previously documented, and a significant number of adverse events, including deaths, have been reported. ^{1 6 7 8 9}

What makes the drug HS135 unique for treating heart failure and pulmonary hypertension?

The drug HS135 is unique because it may work similarly to phosphodiesterase 5 inhibitors like sildenafil, which have shown potential in improving exercise capacity and quality of life in patients with heart failure and pulmonary hypertension by lowering pulmonary vascular resistance. ^{1 3 5 10 11}

Research Team

Monique Champagne, M.Sc.

Principal Investigator

35Pharma Inc

Eligibility Criteria

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 experience moderate to severe symptoms of heart failure.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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 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]

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 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]

References

1. United States 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. [2020]

2. Hungary pubmed.ncbi.nlm.nih.gov

Therapeutic benefits of phosphodiesterase-5 inhibition in chronic heart failure: A meta-analysis. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of sildenafil for pulmonary hypertension due to left heart disease with HFrEF. [2022]

5. England 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. [2015]

6. United States 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. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Selexipag treatment in patients with systemic sclerosis-associated pulmonary arterial hypertension in clinical practice, a case series. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Reported sildenafil side effects in pediatric pulmonary hypertension patients. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Pulmonary Hypertension Therapy and a Systematic Review of Efficacy and Safety of PDE-5 Inhibitors. [2018]

10. England 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. [2022]

11. Egypt 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. [2019]