Sotatercept for Pulmonary Arterial Hypertension
Recruiting in Palo Alto (17 mi)
Overseen byYogesh Reddy, MBBS
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Mayo Clinic
Disqualifiers: Recent heart attack, Stroke, Anemia, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?The purpose of this study is to see if the drug sotatercept given for 36 weeks improves the functioning of the heart and improves quality of life.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have started a new pulmonary vasodilator in the last 60 days.
What data supports the effectiveness of the drug Sotatercept for treating Pulmonary Arterial Hypertension?
Research shows that adding sotatercept to existing treatments for pulmonary arterial hypertension improved patients' ability to walk further in 6 minutes after 24 weeks. Additionally, sotatercept significantly reduced the resistance in blood vessels in the lungs, which is a key factor in this condition.
12345What makes the drug Sotatercept unique for treating pulmonary arterial hypertension?
Sotatercept is unique because it works by targeting specific pathways involved in the disease process, potentially offering a novel mechanism of action compared to existing treatments for pulmonary arterial hypertension.
678910Eligibility Criteria
This trial is for individuals with Pulmonary Arterial Hypertension (PAH), a type of high blood pressure affecting the arteries in the lungs and heart. Participants should have PAH diagnosis and meet specific health criteria not detailed here.Inclusion Criteria
I haven't started any new lung blood pressure medication in the last 60 days.
Informed consent obtained before any trial-related activities
LVEF ≥ 40 % within the preceding year
+3 more
Exclusion Criteria
I haven't had a heart attack, stroke, or severe heart issues in the last 30 days.
I am scheduled for a procedure to improve blood flow to my heart, neck, or limbs.
I am not pregnant, breastfeeding, planning to become pregnant, or if I can have children, I am using effective birth control.
+9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive sotatercept therapy administered as a subcutaneous injection once every 3 weeks for 36 weeks
36 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests if sotatercept, administered over 36 weeks, can enhance heart function and quality of life in PAH patients. It's an investigation into the drug's long-term effects on cardiopulmonary performance during exercise.
1Treatment groups
Experimental Treatment
Group I: Sotatercept TherapyExperimental Treatment1 Intervention
All participants will receive 36 weeks of sotatercept therapy. Sotatercept is administered as a subcutaneous injection once every 3 weeks.
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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mayo Clinic in RochesterRochester, MN
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Who Is Running the Clinical Trial?
Mayo ClinicLead Sponsor
References
Population Health Model Predicting the Long-Term Impact of Sotatercept on Morbidity and Mortality in Patients with Pulmonary Arterial Hypertension (PAH). [2023]Pulmonary arterial hypertension (PAH) is a rare, progressive disease associated with significant morbidity and mortality. The phase 3 STELLAR trial tested sotatercept plus background therapy (BGT) versus placebo plus BGT. BGT was comprised of mono-, double-, or triple-PAH targeted therapy. Building on STELLAR findings, we employed a population health model to assess the potential long-term clinical impact of sotatercept.
Sotatercept for the Treatment of Pulmonary Arterial Hypertension. [2021]Pulmonary arterial hypertension is characterized by pulmonary vascular remodeling, cellular proliferation, and poor long-term outcomes. Dysfunctional bone morphogenetic protein pathway signaling is associated with both hereditary and idiopathic subtypes. Sotatercept, a novel fusion protein, binds activins and growth differentiation factors in the attempt to restore balance between growth-promoting and growth-inhibiting signaling pathways.
In symptomatic PAH, adding sotatercept to stable background therapy improved 6-min walk distance at 24 wk. [2023]Label="SOURCE CITATION">Hoeper MM, Badesch DB, Ghofrani HA, et al; STELLAR Trial Investigators. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med. 2023;388:1478-1490. 36877098.
Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. [2023]Pulmonary arterial hypertension is a progressive disease involving proliferative remodeling of the pulmonary vessels. Despite therapeutic advances, the disease-associated morbidity and mortality remain high. Sotatercept is a fusion protein that traps activins and growth differentiation factors involved in pulmonary arterial hypertension.
Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension. [2023]In participants with pulmonary arterial hypertension, 24 weeks of sotatercept resulted in a significantly greater reduction from baseline in pulmonary vascular resistance than placebo. This report characterises the longer-term safety and efficacy of sotatercept in the PULSAR open-label extension. We report cumulative safety, and efficacy at months 18-24, for all participants treated with sotatercept.
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]Pasireotide (SOM230), a novel multireceptor ligand somatostatin analog (SSA), binds with high affinity to four of the five somatostatin receptor subtypes (sst1-3, 5). This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics profiles of pasireotide long-acting release (LAR) formulation in patients with advanced gastroenteropancreatic neuroendocrine tumor (GEP NET) refractory to other SSAs.
Activation of somatostatin receptors attenuates pulmonary fibrosis. [2014]Somatostatin analogues may have antifibrotic properties in the lung. The aim of this study was to evaluate the expression of the five somatostatin receptors sst1 to sst5 in normal and fibrotic mouse lung and the action of SOM230 (pasireotide), a new somatostatin analogue with a long half-life, in bleomycin induced lung fibrosis and in human lung fibroblasts in vitro.
Ligand-dependent mechanisms of sst2A receptor trafficking: role of site-specific phosphorylation and receptor activation in the actions of biased somatostatin agonists. [2021]The somatostatin receptor subtype 2A (sst2A) mediates many of somatostatin's neuroendocrine actions and is the primary therapeutic target for the stable somatostatin analogs used to inhibit hormone secretion by pituitary and gastroenteropancreatic tumors. Two new multireceptor targeting somatostatin analogs currently under clinical investigation, the multisomatostatin receptor agonist cyclo-[diaminoethylcarbamoyl-HydroxyPro-Phenylglycine-D-Trp-Lys-(4-O-benzyl)Tyr-Phe] (SOM230) (Pasireotide) and pan-somatostatin receptor agonist Tyr-cyclo-[D-diaminobutyric acid-Arg-Phe-Phe-D-Trp-Lys-Thr-Phe] (KE108), behave as functionally selective ligands at the sst2A receptor, mimicking some of somatostatin's actions but antagonizing others. Further, SOM230 and KE108 are less able to induce receptor internalization than somatostatin, indicating that they exhibit functional selectivity for receptor regulation as well as signaling. Here, we identify agonist-specific differences in the molecular events regulating sst2A receptor endocytosis. SOM230 and KE108 were less potent and less effective than somatostatin at stimulating sst2A receptor phosphorylation at two pairs of residues, Ser341/343 and Thr353/354. Only the pattern of Thr353/354 phosphorylation correlated with receptor internalization, consistent with the known importance of Thr phosphorylation for sst2A receptor endocytosis. As expected, arrestin recruitment to membrane receptors was reduced with SOM230 and KE108. In addition, both receptor dephosphorylation and receptor recycling occurred more rapidly with SOM230 and KE108 than with somatostatin. Surprisingly, however, SOM230 and KE108 also altered sst2A internalization in a phosphorylation-independent manner, because these analogs were less effective than somatostatin at stimulating the endocytosis of a phosphorylation-negative receptor mutant. These results show that the decreased receptor internalization produced by SOM230 and KE108 compared with somatostatin result from phosphorylation-independent effects as well as reduced site-specific receptor phosphorylation and receptor-arrestin association.
Somatostatin receptors in non-neuroendocrine malignancies: the potential role of somatostatin analogs in solid tumors. [2014]Somatostatin receptors (sstrs) are G-protein-coupled receptors that mediate various physiological effects when activated by the neuropeptide somatostatin or its synthetic analogs. In addition to the well-documented antisecretory effects of sstr(2)-preferential somatostatin analogs octreotide and lanreotide, ligand binding to sstr initiates an inhibitory action on tumor growth. This effect may result from both indirect actions (suppression of growth factors and growth-promoting hormones [e.g., GH/IGF-1 axis] and inhibition of angiogenesis) and direct actions (activation of antigrowth activities [e.g., apoptosis]). As solid tumor cells express multiple sstrs, there is a rationale to evaluate the potential antitumor effects of pasireotide (SOM230), a multireceptor-targeted somatostatin analog with high binding affinity for sstr(1-3) and sstr(5). Pasireotide reduces systemic IGF-1 levels more potently than currently available somatostatin analogs and has been well tolerated in clinical trials.
Targeted paclitaxel-octreotide conjugates inhibited the growth of paclitaxel-resistant human non-small cell lung cancer A549 cells in vitro. [2022]The application of chemotherapy in non-small cell lung cancer (NSCLC) is limited by the toxicity to normal cells and the development of multi-drug resistance. Targeted chemotherapy using cytotoxic analogs against specific receptors on cancer cells could be a less toxic and more efficacious approach. We identified that the expressions of somatostatin receptor (SSTR) 2 and 5 in tumor tissues from NSCLC patients were higher than those in the adjacent normal tissues by immunohistochemistry, and therefore, cytotoxic somatostatin analogues might be applied for SSTRs-mediated targeted therapy against NSCLC. Two cytotoxic analogs, paclitaxel-octreotide (PTX-OCT) and 2paclitaxel-octreotide (2PTX-OCT), were synthesized by linking one or two molecules of paclitaxel to one molecule of somatostatin analog octreotide. PTX-OCT and 2PTX-OCT significantly inhibited the growth and induced apoptosis of SSTR2- and SSTR5-positive A549 cells, compared with the control (p