Sotatercept for Pulmonary Arterial Hypertension

(MOONBEAM Trial)

Recruiting at 36 trial locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Merck Sharp & Dohme LLC

Must be taking: PDE5 inhibitors, ERAs, sGCS, prostanoids

Disqualifiers: Left-sided heart disease, Eisenmenger syndrome, pulmonary veno-occlusive diseases, coronary disease, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called sotatercept to see if it is safe and how it acts in children with high blood pressure in the lungs, who are already on standard treatments. The study will last for several months. Sotatercept has shown promise in improving exercise tolerance in adults with pulmonary arterial hypertension.

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

No, you must be on a stable dose of your current PAH medications to participate in the trial.

What data supports the idea that Sotatercept for Pulmonary Arterial Hypertension is an effective treatment?

The available research shows that Sotatercept is effective for treating Pulmonary Arterial Hypertension. In a study, patients who took Sotatercept along with their regular treatment were able to walk farther in six minutes after 24 weeks compared to those who did not take it. Another study found that Sotatercept significantly reduced the resistance in blood vessels in the lungs, which is a good sign for improving the condition. These results suggest that Sotatercept can help improve physical ability and reduce the strain on the heart in people with this condition. ^{1 2 3 4 5}

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

The provided research does not contain any safety data for Sotatercept or its other names (Winrevair, ACE-011, MK-7962, sotatercept-csrk) in the context of pulmonary arterial hypertension or any other condition. The studies focus on different drugs and conditions, such as pasireotide for neuroendocrine tumors and psychiatric adverse reactions to non-selective RET multi-kinase inhibitors. ^{6 7 8 9 10}

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

The provided research articles do not contain information about Sotatercept or its effects on Pulmonary Arterial Hypertension. Therefore, based on the given data, we cannot determine if Sotatercept is a promising treatment for this condition. ^{6 11 12 13 14}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for children aged 1 to under 18 with Pulmonary Arterial Hypertension (PAH) who are already on stable PAH therapy. They must have a confirmed diagnosis and agree to contraception rules if applicable. It's not for those with certain heart or lung conditions, prior severe allergic reactions, or a family history of sudden cardiac death.

Inclusion Criteria

I am following the required birth control guidelines.

I have a confirmed diagnosis of PAH Group 1 through a right heart catheterization.

I am on a consistent dose of medication for pulmonary arterial hypertension.

Exclusion Criteria

I have had heart disease symptoms recently.

I have had heart disease affecting the left side of my heart.

I have a history of lung or heart conditions.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a subcutaneous injection of Sotatercept every 3 weeks for 24 weeks

24 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Sotatercept (Other)

Trial Overview The study tests the safety, tolerability, and how the body processes Sotatercept over 24 weeks in kids with PAH while they continue their standard treatments. There's no specific hypothesis; it's more about understanding these aspects of the drug in young patients.

Participant Groups

Group I: Children ≥1 to <18 years old Experimental Treatment 1 Intervention

Participants will receive a subcutaneous (SC) injection every 3 weeks (Q3W) of 0.3 mg/kg. Dosage may be adjusted based on protocol-specific guidelines.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

The Phase 3 STELLAR trial demonstrated that sotatercept significantly improves exercise capacity and reduces pulmonary vascular resistance in patients with pulmonary arterial hypertension, indicating its efficacy as a treatment option.

The study involved a large cohort of patients, providing robust evidence for the safety and effectiveness of sotatercept in managing this serious condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In symptomatic PAH, adding sotatercept to stable background therapy improved 6-min walk distance at 24 wk. Estrada, RA.[2023]

In a phase 3 trial involving 323 adults with pulmonary arterial hypertension, sotatercept significantly improved exercise capacity, as measured by a 34.4 m increase in the 6-minute walk distance compared to just 1.0 m in the placebo group, indicating its efficacy in enhancing physical performance.

Sotatercept also showed significant improvements across multiple secondary endpoints related to pulmonary health, although it was associated with some adverse effects like epistaxis and increased blood pressure, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. Hoeper, MM., Badesch, DB., Ghofrani, HA., et al.[2023]

In a study involving 106 participants with pulmonary arterial hypertension, sotatercept demonstrated significant long-term efficacy in reducing pulmonary vascular resistance and improving functional outcomes over 24 months, with sustained benefits observed in both groups receiving sotatercept.

The treatment was generally safe, with serious adverse events occurring in 30.8% of participants, but only a small number (2.9%) of deaths were reported, none linked to the drug, indicating a favorable safety profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension. Humbert, M., McLaughlin, V., Gibbs, JSR., et al.[2023]

The phase 3 STELLAR trial indicated that adding sotatercept to background therapy for pulmonary arterial hypertension (PAH) significantly increases life expectancy, with an estimated gain of 11.5 years per patient compared to background therapy alone.

Sotatercept also reduces the need for infused prostacyclin treatments, hospitalizations due to PAH, and the number of lung/heart-lung transplants required, suggesting it may improve overall patient management in PAH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Health Model Predicting the Long-Term Impact of Sotatercept on Morbidity and Mortality in Patients with Pulmonary Arterial Hypertension (PAH). McLaughlin, V., Alsumali, A., Liu, R., et al.[2023]

In a 24-week trial involving 106 adults with pulmonary arterial hypertension, sotatercept significantly reduced pulmonary vascular resistance compared to placebo, indicating its efficacy in improving this condition.

Sotatercept also improved exercise capacity, as shown by a greater increase in 6-minute walk distance in the treatment groups, although some hematologic adverse events were noted, including thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotatercept for the Treatment of Pulmonary Arterial Hypertension. Humbert, M., McLaughlin, V., Gibbs, JSR., et al.[2021]

Pasireotide long-acting release (LAR) formulation was well tolerated in patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP NET), with 81% of participants reporting adverse events, primarily mild symptoms like diarrhea and fatigue.

The study achieved steady-state plasma levels of pasireotide after three monthly injections, indicating effective drug delivery and potential for sustained therapeutic effects in patients refractory to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, pharmacokinetics, and pharmacodynamics of a long-acting release (LAR) formulation of pasireotide (SOM230) in patients with gastroenteropancreatic neuroendocrine tumors: results from a randomized, multicenter, open-label, phase I study. Wolin, EM., Hu, K., Hughes, G., et al.[2022]

Lutetium Lu-177 dotatate is an effective treatment for gastroenteropancreatic neuroendocrine tumors, significantly improving progression-free survival, as shown in European studies.

In a study of 12 patients, tumor flare reactions were observed in 5 patients, but these reactions can be effectively managed with corticosteroids or other strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu-177 Dotatate Flare Reaction. Salner, AL., Blankenship, B., Dunnack, H., et al.[2022]

A study analyzing 1,108 reports of psychiatric adverse events (AEs) related to non-selective RET multi-kinase inhibitors (MKIs) found that these drugs, particularly sorafenib, sunitinib, cabozantinib, and lenvatinib, are significantly associated with serious psychiatric side effects, including hospitalization and even death.

The highest death rate from psychiatric AEs was observed with sunitinib (44.4%), highlighting the need for clinicians to closely monitor patients for these potentially fatal side effects when administering these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychiatric adverse reactions to non-selective RET multi-kinase inhibitors: a large-scale pharmacovigilance analysis. Wang, X., Yin, D., Tang, Y., et al.[2023]

The novel somatostatin receptor antagonist [177Lu]Lu-satoreotide tetraxetan demonstrated a promising disease control rate of 94.7% in 40 patients with progressive neuroendocrine tumors, indicating its potential efficacy as a treatment option.

The treatment had an acceptable safety profile, with no severe nephrotoxicity observed, although 42.5% of patients experienced grade 3 or higher treatment-related adverse events, primarily affecting blood cell counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II study of the safety and efficacy of [177Lu]Lu-satoreotide tetraxetan in advanced somatostatin receptor-positive neuroendocrine tumours. Wild, D., Grønbæk, H., Navalkissoor, S., et al.[2023]

The NETTER-1 trial, a phase III clinical study, showed that peptide receptor radionuclide therapy using 177Lu-DOTATATE significantly improves progression-free survival in patients with midgut neuroendocrine tumors compared to high-dose octreotide.

This therapy targets somatostatin receptors on neuroendocrine tumors, highlighting its efficacy as a systemic radiotherapy option for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide Receptor Radiotherapy Comes of Age. Al-Toubah, T., Strosberg, J.[2019]

Cytotoxic somatostatin analogs, specifically paclitaxel-octreotide (PTX-OCT) and 2paclitaxel-octreotide (2PTX-OCT), effectively target non-small cell lung cancer (NSCLC) cells expressing somatostatin receptors (SSTR) 2 and 5, leading to significant growth inhibition and apoptosis in these cancer cells.

These PTX-OCT conjugates show promise in overcoming paclitaxel resistance, as they induce lower levels of the MDR-1 gene associated with drug resistance, making them a potentially safer and more effective treatment option for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted paclitaxel-octreotide conjugates inhibited the growth of paclitaxel-resistant human non-small cell lung cancer A549 cells in vitro. Liu, Y., Xia, H., Wang, Y., et al.[2022]

SOM230, a somatostatin analogue, significantly improved survival rates in mice with bleomycin-induced lung fibrosis (69% vs 44%) and reduced lung collagen content, indicating its potential efficacy in treating pulmonary fibrosis.

The study demonstrated that SOM230 not only decreased inflammation and collagen production in mouse lungs but also inhibited the activation of human lung fibroblasts in vitro, suggesting a promising mechanism for its antifibrotic properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activation of somatostatin receptors attenuates pulmonary fibrosis. Borie, R., Fabre, A., Prost, F., et al.[2014]

References

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

In symptomatic PAH, adding sotatercept to stable background therapy improved 6-min walk distance at 24 wk. [2023]

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

Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension. [2023]

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

Population Health Model Predicting the Long-Term Impact of Sotatercept on Morbidity and Mortality in Patients with Pulmonary Arterial Hypertension (PAH). [2023]

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

Sotatercept for the Treatment of Pulmonary Arterial Hypertension. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Safety, tolerability, pharmacokinetics, and pharmacodynamics of a long-acting release (LAR) formulation of pasireotide (SOM230) in patients with gastroenteropancreatic neuroendocrine tumors: results from a randomized, multicenter, open-label, phase I study. [2022]

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

Lutetium Lu-177 Dotatate Flare Reaction. [2022]

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

Psychiatric adverse reactions to non-selective RET multi-kinase inhibitors: a large-scale pharmacovigilance analysis. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

A phase I/II study of the safety and efficacy of [177Lu]Lu-satoreotide tetraxetan in advanced somatostatin receptor-positive neuroendocrine tumours. [2023]

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

Peptide Receptor Radiotherapy Comes of Age. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Somatostatin receptors in non-neuroendocrine malignancies: the potential role of somatostatin analogs in solid tumors. [2014]

12. Singapore pubmed.ncbi.nlm.nih.gov

Targeted paclitaxel-octreotide conjugates inhibited the growth of paclitaxel-resistant human non-small cell lung cancer A549 cells in vitro. [2022]

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

Activation of somatostatin receptors attenuates pulmonary fibrosis. [2014]

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

Ligand-dependent mechanisms of sst2A receptor trafficking: role of site-specific phosphorylation and receptor activation in the actions of biased somatostatin agonists. [2021]