HS135 for Pulmonary Arterial Hypertension

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests HS135, an experimental treatment for Pulmonary Arterial Hypertension (PAH), a condition characterized by high blood pressure in the lungs' arteries. The goal is to determine if HS135 can help manage symptoms and improve the condition in adults. Participants must have a PAH diagnosis, experience symptoms affecting daily life, and currently be on at least two stable PAH treatments. 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.

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.

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

Research has shown that HS135 has been safe in studies so far. For example, in animal studies, doses of 3 or 30 mg/kg of HS135 did not alter blood results, indicating good tolerance. This finding reassures researchers as they begin testing it in humans.

This stage of research is the first to involve human participants. Although extensive safety data is not yet available, the primary focus is ensuring HS135's safety for people. The goal is to observe how the body reacts to the treatment and monitor for any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Pulmonary Arterial Hypertension, which typically include oral medications, inhaled therapies, or intravenous infusions, HS135 is administered as a subcutaneous injection. Researchers are excited about HS135 because it offers a new delivery method that could potentially improve convenience and patient adherence compared to more invasive or cumbersome options. Additionally, this novel approach might provide a more consistent and controlled release of the medication, potentially leading to better management of symptoms.

What evidence suggests that HS135 might be an effective treatment for pulmonary arterial hypertension?

Research shows that HS135, the investigational treatment studied in this trial, may be promising for pulmonary arterial hypertension (PAH). HS135 is a new treatment that helps balance certain proteins in the body. It works better than similar treatments at reducing lung inflammation. Studies have also shown that HS135 improves heart and lung function in models of pulmonary hypertension. Importantly, HS135 has been well tolerated, meaning it doesn't cause serious side effects that would limit its use. These findings suggest HS135 could be a strong option for treating PAH. ^{1 2 4 6 7}

Who Is on the Research Team?

Monique Champagne, M.Sc.

Principal Investigator

VP, Clinical Operations

Are You a Good Fit for This Trial?

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

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

Left ventricular ejection fraction < 50% at screening

PFT values of FVC and or FEV1 < 60% predicted at the screening visit or within 6 months prior to the screening visit

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: HS135 Experimental Treatment 1 Intervention

Subcutaneous Injection

Who Is Running the Clinical Trial?

35Pharma Inc

Lead Sponsor

Trials

3

Recruited

120+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

Citations

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

Abstract 10487: In vivo Efficacy of HS135, a Novel Activin ... Conclusions: Contrary to other ActR-based therapies, HS135 did not lead to increases in hematocrit which would limit its dosing. HS135 was ...

2. 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.

3. 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 ...

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 ... Similarly, in the lung, HS135 was more efficacious than ActRIIA-Fc at improving inflammation markers and rebalancing Activin and BMP signalling.

5. publications.ersnet.org publications.ersnet.org/content/erj/62/suppl67/pa450

HS135, A Novel Activin and GDF Trap, is Highly Efficacious in ... Conclusion: The best-in-class target engagement profile of HS135 translates into superior and differentiated heart and lung efficacy in Group 1 and 2 PH models, ...

6. delta.larvol.com delta.larvol.com/Products/?ProductId=b2c8cf91-b50e-43d6-a21c-24e8333b904f

HS135 / 35Pharma A Study of HS135 for the Treatment of Pulmonary Arterial Hypertension in Adults ... data to evaluate safety, identify efficacy signals and inform further ...

7. synapse.patsnap.com synapse.patsnap.com/drug/4c5f1f003dd07f0d45c4a6da1c5dfdc1

HS-135 - Drug Targets, Indications, Patents Assessing the pharmacokinetics, safety, pharmacodynamics, and efficacy of HS135 in obese patients with pulmonary hypertension and heart failure with preserved ...