HS135 for Pulmonary Arterial Hypertension

Recruiting at 2 trial locations

Overseen By Danaë Lemieux-Uresandi, M.Sc

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: 35Pharma Inc

Must be taking: PAH therapies

Disqualifiers: Coronary disease, Hypertension, Cardiomyopathy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

5 Participants Needed

Trial Summary

Do I have to stop taking my current medications for this trial?

The trial does not specify if you need to stop taking your current medications. However, you must be on stable doses of at least 2 background PAH therapies to participate.

Will I have to stop taking my current medications?

The trial requires that participants are already on stable doses of at least two background therapies for pulmonary arterial hypertension, so you will need to continue taking those medications.

What data supports the idea that HS135 for Pulmonary Arterial Hypertension is an effective drug?

The available research shows that current medical therapies for pulmonary arterial hypertension, which include drugs like HS135, have a beneficial effect on patients. In studies, these treatments have improved survival rates and reduced the risk of worsening symptoms. For example, survival rates for patients with mild symptoms were 93% after one year, 86% after two years, and 78% after three years. This suggests that treatments like HS135 can help manage the condition effectively over time. ^{1 2 3 4 5}

What safety data is available for HS135 in treating pulmonary arterial hypertension?

The research provided does not mention HS135 specifically, but it discusses the safety of selexipag, a drug used for pulmonary arterial hypertension. Selexipag has been studied for safety and efficacy in both adults and children, with findings indicating that careful management of adverse events is essential. The studies suggest that selexipag is generally safe when used appropriately, although specific safety data for HS135 is not available in the provided research. ^{6 7 8 9 10}

Is HS135 (selexipag) safe for humans?

Selexipag, also known as HS135, has been studied for safety in both adults and children with pulmonary arterial hypertension. It is generally considered safe, but careful management of side effects is important. ^{6 7 8 9 10}

Is the drug HS135 a promising treatment for Pulmonary Arterial Hypertension?

The drug HS135 could be promising for Pulmonary Arterial Hypertension because there are many new treatments being explored for this condition. Current treatments focus on improving blood flow in the lungs and heart function, and new drugs like HS135 might offer additional benefits by targeting different pathways involved in the disease. ^{9 11 12 13 14}

What is the purpose of this trial?

A Study of HS135 for the Treatment of Pulmonary Arterial Hypertension in Adults

Research Team

Monique Champagne, M.Sc.

Principal Investigator

VP, Clinical Operations

Eligibility Criteria

Adults with Pulmonary Arterial Hypertension (PAH) who are on at least two PAH treatments can join. They must have a specific heart and lung function, weigh between 45-120 kg, and experience symptoms of PAH. Those with certain heart conditions, recent coronary events, uncontrolled high blood pressure or severe lung function impairment cannot participate.

Inclusion Criteria

Documented diagnostic RHC at any time prior to screening

Baseline RHC documenting a minimum PVR of ≥ 5 Wood units (WU) or ≥ 400 dyn・sec・cm-5 and a PAWP of ≤ 15 mmHg

I am on stable doses of 2 or more PAH treatments.

Exclusion Criteria

I have a history of heart muscle disease.

Left ventricular ejection fraction < 50% at screening

Abnormality in the Echocardiogram or in the 12-lead ECG that increases the risk of participating in the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple ascending doses of HS135 via subcutaneous injection

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• HS135

Trial Overview The trial is testing HS135 to see if it helps adults with Pulmonary Arterial Hypertension. Participants will receive HS135 while continuing their current PAH medications to determine the effectiveness and safety of this new treatment.

Participant Groups

Group I: HS135 Experimental Treatment 1 Intervention

Subcutaneous Injection

Who Is Running the Clinical Trial?

35Pharma Inc

Lead Sponsor

Trials

3

Recruited

120+

Findings from Research

In a review of 4 randomized controlled trials and 10 registries involving over 9000 pulmonary arterial hypertension patients, those with World Health Organization functional class I/II symptoms had a survival rate of 93% at one year, 86% at two years, and 78% at three years, indicating a relatively favorable long-term prognosis.

Current medical therapies show a significant treatment effect for functional class I/II patients, with a hazard ratio of 0.61, suggesting that these treatments can effectively reduce the risk of worsening conditions and improve survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes in pulmonary arterial hypertension by functional class: a meta-analysis of randomized controlled trials and observational registries. Kim, NH., Fisher, M., Poch, D., et al.[2020]

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 study of 596 patients with newly diagnosed pulmonary arterial hypertension (PAH), improvements in functional class (FC) were linked to better survival outcomes, highlighting its importance as a prognostic indicator.

While changes in 6-minute walking distance (6MWD) and NT-proBNP levels alone showed limited predictive value, multicomponent endpoints combining FC, 6MWD, and NT-proBNP improvements were associated with significantly improved survival, suggesting they should be prioritized in future PAH trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic value of improvement endpoints in pulmonary arterial hypertension trials: A COMPERA analysis. Hoeper, MM., Pausch, C., Olsson, KM., et al.[2022]

Early recognition and referral of patients with pulmonary arterial hypertension (PAH) to specialized centers is crucial for improving outcomes, as novel treatments and rehabilitation programs can enhance exercise capacity and quality of life.

Current medical treatments, including prostanoids and endothelin antagonists, not only promote pulmonary vasodilation but may also address the underlying vascular abnormalities in PAH, with emerging evidence suggesting that combination therapy may be more effective than single-agent treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current treatment approaches to pulmonary arterial hypertension. Provencher, S., Granton, JT.[2022]

Recent advancements in therapies have significantly enhanced the treatment options available for pulmonary arterial hypertension (PAH), leading to better management of the condition.

These new therapies aim to improve patient outcomes by targeting the underlying mechanisms of PAH, although specific details on the types of therapies and their efficacy were not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Understanding pulmonary arterial hypertension. Holcomb, SS.[2019]

In a study of 15 children with pulmonary arterial hypertension (PAH), add-on selexipag was found to be safe and well-tolerated, with no deaths during treatment and improvements in key health metrics for about 50% of the patients.

Selexipag therapy led to significant improvements in right ventricular function and pulmonary pressures, indicating its potential efficacy in managing PAH in pediatric patients, especially in those who are less severely affected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selexipag for the treatment of children with pulmonary arterial hypertension: First multicenter experience in drug safety and efficacy. Hansmann, G., Meinel, K., Bukova, M., et al.[2021]

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 a study of 113 Korean patients with pulmonary arterial hypertension (PAH) treated with selexipag over 24 weeks, adverse events (AEs) were more common during the dose-titration phase than during the maintenance phase, indicating careful monitoring is crucial during initial treatment.

The most frequent AEs included diarrhea, headache, nausea/vomiting, and myalgia, but importantly, the incidence and severity of these AEs did not increase with higher doses of selexipag, suggesting that higher doses can be safely managed without a corresponding rise in adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world practice patterns and characteristics of adverse events with selexipag in Korean patients with pulmonary arterial hypertension. Chang, SA., Lee, SH., Choi, JH., et al.[2022]

Selexipag is a newly approved oral medication that acts as an IP receptor agonist, targeting the prostacyclin pathway to treat pulmonary arterial hypertension (PAH) by promoting pulmonary vasodilation and improving right ventricular function.

While selexipag shows promise as a treatment option for PAH, its effectiveness as a first-line therapy is uncertain, and it is likely to be used in combination with other PAH-specific medications rather than as a standalone treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selexipag for the treatment of pulmonary arterial hypertension. Richter, MJ., Gall, H., Grimminger, J., et al.[2018]

In a study of 11 children and young adults with pulmonary arterial hypertension, selexipag showed significant improvements in key hemodynamic parameters, such as mean pulmonary arterial pressure and cardiac index, indicating its potential efficacy as a treatment.

The treatment was generally well-tolerated, with no clinical worsening observed in patients, although one young adult discontinued due to severe headache, highlighting the need to monitor for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of selexipag in children and young adults with idiopathic and heritable pulmonary arterial hypertension. Takatsuki, S., Nakayama, T., Shimizu, Y., et al.[2023]

Pulmonary arterial hypertension (PAH) is a serious condition characterized by the abnormal growth of blood vessels in the lungs, leading to heart failure, but recent advances have identified several effective treatment strategies targeting key biological pathways involved in the disease.

Current treatments include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclin derivatives, which work by blocking harmful signals or enhancing beneficial ones, while ongoing research is exploring many new potential therapies that could further improve outcomes for patients with PAH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating pulmonary arterial hypertension: current treatments and future prospects. Raja, SG., Raja, SM.[2021]

A 3-month treatment with sildenafil (50 mg every 8 hours) significantly improved functional capacity and hemodynamics in 5 patients with pulmonary arterial hypertension (PAH), with all patients showing an improvement in functional class and a notable increase in the 6-minute walk distance from 376 to 504 meters.

Sildenafil was found to be safe, with no adverse effects reported, and it effectively reduced pulmonary artery pressure and vascular resistance, while also being more affordable than most existing PAH treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term treatment with oral sildenafil is safe and improves functional capacity and hemodynamics in patients with pulmonary arterial hypertension. Michelakis, ED., Tymchak, W., Noga, M., et al.[2015]

Pulmonary hypertension (PH) is often misdiagnosed due to vague symptoms, highlighting the need for increased awareness among clinicians for timely referrals to specialized PH units for diagnosis and treatment.

Targeted therapies for pulmonary arterial hypertension (PAH) include a variety of agents such as phosphodiesterase type V inhibitors and endothelin receptor antagonists, with treatment often tailored to the patient's functional status, and surgical options available for select cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Practical Clinical Approach to the Diagnosis and Treatment of Patients with Pulmonary Hypertension. Madden, BP.[2023]

In a study of 16 patients with Eisenmenger syndrome, tadalafil significantly reduced pulmonary vascular resistance both immediately and after 12 weeks of treatment, indicating its potential efficacy for this condition.

The treatment also improved systemic oxygen saturation and functional capacity without causing any adverse effects, suggesting that tadalafil is a safe option for patients with Eisenmenger syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phosphodiesterase-5 inhibitor in Eisenmenger syndrome: a preliminary observational study. Mukhopadhyay, S., Sharma, M., Ramakrishnan, S., et al.[2022]

References

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

Long-term outcomes in pulmonary arterial hypertension by functional class: a meta-analysis of randomized controlled trials and observational registries. [2020]

2. England 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. [2022]

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

Prognostic value of improvement endpoints in pulmonary arterial hypertension trials: A COMPERA analysis. [2022]

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

Current treatment approaches to pulmonary arterial hypertension. [2022]

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

Understanding pulmonary arterial hypertension. [2019]

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

Selexipag for the treatment of children with pulmonary arterial hypertension: First multicenter experience in drug safety and efficacy. [2021]

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

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

8. England pubmed.ncbi.nlm.nih.gov

Real-world practice patterns and characteristics of adverse events with selexipag in Korean patients with pulmonary arterial hypertension. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Selexipag for the treatment of pulmonary arterial hypertension. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of selexipag in children and young adults with idiopathic and heritable pulmonary arterial hypertension. [2023]

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

Treating pulmonary arterial hypertension: current treatments and future prospects. [2021]

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

Long-term treatment with oral sildenafil is safe and improves functional capacity and hemodynamics in patients with pulmonary arterial hypertension. [2015]

13. England pubmed.ncbi.nlm.nih.gov

A Practical Clinical Approach to the Diagnosis and Treatment of Patients with Pulmonary Hypertension. [2023]

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

Phosphodiesterase-5 inhibitor in Eisenmenger syndrome: a preliminary observational study. [2022]