Sotatercept for Pulmonary Arterial Hypertension

(MOONBEAM Trial)

Recruiting at 48 trial locations

Overseen By Toll Free Number

Age: < 18

Sex: Any

Trial Phase: Phase 2

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called sotatercept (also known as Winrevair, ACE-011, or MK-7962) to determine its safety and effectiveness for children with pulmonary arterial hypertension (PAH), a rare lung condition that hinders blood flow from the heart to the lungs. The study will monitor how the body processes the medication over 24 weeks. Children with PAH who are already on stable medication may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

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.

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

Research has shown that sotatercept has a good safety record from previous studies. The FDA has already approved it for treating pulmonary arterial hypertension (PAH) in adults, indicating it has passed strict safety tests for that purpose. In long-term studies, sotatercept's safety remained stable over time, with no major surprises.

Some people experienced side effects, but these were generally manageable. Common side effects included headaches and nosebleeds, while more serious side effects were rare. Overall, sotatercept is well-tolerated, making it a promising treatment option for PAH. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pulmonary arterial hypertension?

Sotatercept is unique because it works by targeting the underlying mechanisms of pulmonary arterial hypertension (PAH) differently than current treatments. Most standard therapies, like endothelin receptor antagonists or phosphodiesterase-5 inhibitors, aim to relax blood vessels or improve blood flow. In contrast, sotatercept acts on the transforming growth factor-beta (TGF-beta) superfamily pathways, which plays a role in the remodeling of blood vessels. This new mechanism of action has researchers excited as it represents a novel approach to potentially improve outcomes for patients, especially since it can be administered conveniently as a subcutaneous injection every three weeks.

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

Research has shown that sotatercept, also known as WINREVAIR, shows promise for treating pulmonary arterial hypertension (PAH). In studies with adults, sotatercept improved exercise capacity and daily activity performance, enhancing quality of life. It also reduced the risk of the condition worsening, helping to stabilize PAH. Long-term studies support its benefits when combined with other PAH treatments. Overall, these findings suggest sotatercept could effectively manage PAH. ^{2 3 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Sotatercept

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.

How Is the Trial Designed?

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.

Sotatercept is already approved in European Union, United States for the following indications:

Approved in European Union as Winrevair for:

• Pulmonary arterial hypertension (PAH, WHO Group 1)

Approved in United States as Winrevair for:

• Pulmonary arterial hypertension (PAH, WHO Group 1)

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

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

Pasireotide, a multireceptor-targeted somatostatin analog, shows promise in reducing systemic IGF-1 levels more effectively than existing somatostatin analogs, which may enhance its antitumor effects.

The mechanism of action for pasireotide includes both direct inhibition of tumor growth through apoptosis and indirect effects by suppressing growth factors and hormones, making it a potentially effective treatment for solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Somatostatin receptors in non-neuroendocrine malignancies: the potential role of somatostatin analogs in solid tumors. Hasskarl, J., Kaufmann, M., Schmid, HA.[2014]

SOM230 and KE108, two new somatostatin analogs, show functional selectivity at the sst2A receptor, mimicking some actions of somatostatin while antagonizing others, which may enhance their therapeutic potential for treating tumors.

These analogs exhibit reduced receptor internalization compared to somatostatin due to both decreased phosphorylation at specific sites and phosphorylation-independent mechanisms, suggesting a unique regulatory profile that could improve their efficacy in clinical applications.

NCBI (Pubmed)

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. Kao, YJ., Ghosh, M., Schonbrunn, A.[2021]

Citations

1. merck.com merck.com/news/u-s-fda-approves-updated-indication-for-winrevair-sotatercept-csrk-in-adults-with-pulmonary-arterial-hypertension-pah-who-group-1-pulmonary-hypertension-based-on-phase-3-zenith-study/

U.S. FDA Approves Updated Indication for WINREVAIR ... Adding WINREVAIR to background PAH therapy improved exercise capacity and WHO functional class (FC), and reduced the risk of clinical ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2213558

Phase 3 Trial of Sotatercept for Treatment of Pulmonary ... In the phase 3 STELLAR trial, we further investigated the efficacy, safety, and adverse-event profile of sotatercept in combination with stable background ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39978862/

A long-term follow-up study of sotatercept for treatment ... Interim results of SOTERIA support the favourable benefit-risk of add-on sotatercept treatment in adults with PAH. Follow-up reports from ...

4. winrevair.com winrevair.com/clinical-trials-results/

Clinical Trial Results for WINREVAIR™ (sotatercept-csrk) WINREVAIR could improve important measures of heart health and function that help your doctor monitor your PAH. In STELLAR, adults with PAH who added WINREVAIR ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03496207

NCT03496207 | A Study of Sotatercept for the Treatment ... Study A011-09 is designed to assesses the efficacy and safety of sotatercept (ACE-011) relative to placebo in adults with pulmonary arterial hypertension (PAH).

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/761363s000lbl.pdf

WINREVAIR (sotatercept-csrk) for injection - accessdata.fda.gov Uncontrolled Long-term Safety Data. The safety profile ... WINREVAIR™ is a prescription medicine used to treat adults with pulmonary arterial hypertension.

7. merckconnect.com merckconnect.com/winrevair/adverse-reactions/

Adverse Reactions for WINREVAIR™ (sotatercept-csrk) Long-term safety data for WINREVAIR were generally similar to STELLAR data · Consider adding WINREVAIR—a PAH treatment with a demonstrated tolerability profile ...

8. ajmc.com ajmc.com/view/sotatercept-for-pah-maintains-safety-reduced-mortality-in-long-term-follow-up

Sotatercept for PAH Maintains Safety, Reduced Mortality in ... The pulmonary arterial hypertension (PAH) drug preserved its safety profile at 2.5 years of treatment and continued to reduce mortality compared ...