Acute Ischemic Stroke Clinical Trial
Official title:
A Multicentric, Randomized, Double-blind, Parallel, Placebo-controlled Phase III Study to Assess the Safety and Efficacy of Sovateltide in Patients With Acute Cerebral Ischemic Stroke.
Verified date | October 2023 |
Source | Pharmazz, Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Extensive research is being conducted in search of neuroprotective agents for possible use in the acute phase of stroke and agents that can be used for neurorepair in later stages of stroke. Several trials have been conducted and are in progress using different pharmacological agents, but none of the studies involve the stimulation of ETB receptors to treat cerebral ischemic stroke. Sovateltide (IRL-1620, PMZ-1620) has been effective in animal models of cerebral ischemic stroke. Its safety and tolerability have been demonstrated in a human phase I study with 7 subjects. Clinical phase II and III results indicate that sovateltide is a novel, first-in-class, highly effective drug candidate for treating cerebral ischemic stroke. Safety and significant efficacy in improving the National Institutes of Health Stroke Scale (NIHSS), Modified Rankin scale (mRS), and Barthel index (BI) obtained in phase II and III studies in patients with cerebral ischemic stroke in India are convincing and encouraged us to investigate its safety and efficacy in cerebral ischemic stroke patients in the United States. Therefore, the plan is to conduct a phase III clinical study to evaluate the safety and efficacy of sovateltide therapy along with standard of care in patients of acute ischemic stroke.
Status | Not yet recruiting |
Enrollment | 444 |
Est. completion date | November 2025 |
Est. primary completion date | August 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 80 Years |
Eligibility | Inclusion Criteria: A patient will be eligible for inclusion in the study if he/she fulfils the following criteria: 1. Adult males or females aged 18 - 80 years of age 2. Patient or Legally Acceptable Representative (LAR) willing to give informed consent before study procedure 3. Stroke is ischemic in origin and radiologically confirmed Computed Tomography (CT) scan or diagnostic magnetic resonance imaging (MRI) prior to enrolment. No hemorrhage as proved by cerebral CT/MRI scan. 4. Cerebral ischemic stroke patients presenting within 24 hours after onset of symptoms with NIHSS score of = 8 and < 20 as well as NIHSS Level of Consciousness (1A) score < 2 at the time of screening. This includes cerebral ischemic stroke patients who completely recovered from earlier episodes before having a new or fresh stroke. 5. The patient is < 24 hours from time of stroke onset when the first dose of sovateltide is administered. Time of onset is when symptoms began; for stroke that occurred during sleep, time of onset is when the patient was last seen or was self- reported to be normal 6. Reasonable expectation of availability to receive the full sovateltide course of therapy, and to be available for subsequent follow-up visits Exclusion Criteria: A patient will not be eligible for inclusion in this study if they meet any of the following exclusion criteria: 1. Patients receiving endovascular therapy or is a candidate for any surgical intervention for the treatment of stroke, which may include but not limited to endovascular techniques. 2. Patients classified as comatose are defined as a patient who requires repeated stimulation to attend or is obtunded and requires strong or painful stimulation to make movements (NIHSS Level of Consciousness (1A) score = 2) 3. Evidence of intracranial hemorrhage (intracerebral hematoma, intraventricular hemorrhage, subarachnoid hemorrhage (SAH), epidural hemorrhage, acute or chronic subdural hematoma (SDH) on the baseline CT or MRI scan 4. Known pregnancy and lactating women 5. Confounding pre-existing neurological or psychiatric disease 6. Concurrent participation in any other therapeutic clinical trial 7. Evidence of any other major life-threatening or serious medical condition that would prevent completion of the study protocol, impair the assessment of outcome, or in which sovateltide therapy would be contraindicated or might cause harm to the patient |
Country | Name | City | State |
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n/a |
Lead Sponsor | Collaborator |
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Pharmazz, Inc. |
Briyal S, Nguyen C, Leonard M, Gulati A. Stimulation of endothelin B receptors by IRL-1620 decreases the progression of Alzheimer's disease. Neuroscience. 2015 Aug 20;301:1-11. doi: 10.1016/j.neuroscience.2015.05.044. Epub 2015 May 27. — View Citation
Briyal S, Shepard C, Gulati A. Endothelin receptor type B agonist, IRL-1620, prevents beta amyloid (Abeta) induced oxidative stress and cognitive impairment in normal and diabetic rats. Pharmacol Biochem Behav. 2014 May;120:65-72. doi: 10.1016/j.pbb.2014.02.008. Epub 2014 Feb 20. — View Citation
Gulati A, Agrawal N, Vibha D, Misra UK, Paul B, Jain D, Pandian J, Borgohain R. Safety and Efficacy of Sovateltide (IRL-1620) in a Multicenter Randomized Controlled Clinical Trial in Patients with Acute Cerebral Ischemic Stroke. CNS Drugs. 2021 Jan;35(1): — View Citation
Gulati A, Hornick MG, Briyal S, Lavhale MS. A novel neuroregenerative approach using ET(B) receptor agonist, IRL-1620, to treat CNS disorders. Physiol Res. 2018 Jun 27;67(Suppl 1):S95-S113. doi: 10.33549/physiolres.933859. — View Citation
Leonard MG, Briyal S, Gulati A. Endothelin B receptor agonist, IRL-1620, provides long-term neuroprotection in cerebral ischemia in rats. Brain Res. 2012 Jun 29;1464:14-23. doi: 10.1016/j.brainres.2012.05.005. Epub 2012 May 9. — View Citation
Leonard MG, Briyal S, Gulati A. Endothelin B receptor agonist, IRL-1620, reduces neurological damage following permanent middle cerebral artery occlusion in rats. Brain Res. 2011 Oct 28;1420:48-58. doi: 10.1016/j.brainres.2011.08.075. Epub 2011 Sep 7. — View Citation
Leonard MG, Gulati A. Endothelin B receptor agonist, IRL-1620, enhances angiogenesis and neurogenesis following cerebral ischemia in rats. Brain Res. 2013 Aug 28;1528:28-41. doi: 10.1016/j.brainres.2013.07.002. Epub 2013 Jul 11. — View Citation
Leonard MG, Prazad P, Puppala B, Gulati A. Selective Endothelin-B Receptor Stimulation Increases Vascular Endothelial Growth Factor in the Rat Brain during Postnatal Development. Drug Res (Stuttg). 2015 Nov;65(11):607-13. doi: 10.1055/s-0034-1398688. Epub 2015 Mar 25. — View Citation
Ramos MD, Briyal S, Prazad P, Gulati A. Neuroprotective Effect of Sovateltide (IRL 1620, PMZ 1620) in a Neonatal Rat Model of Hypoxic-Ischemic Encephalopathy. Neuroscience. 2022 Jan 1;480:194-202. doi: 10.1016/j.neuroscience.2021.11.027. Epub 2021 Nov 23. — View Citation
Ranjan AK, Briyal S, Gulati A. Sovateltide (IRL-1620) activates neuronal differentiation and prevents mitochondrial dysfunction in adult mammalian brains following stroke. Sci Rep. 2020 Jul 29;10(1):12737. doi: 10.1038/s41598-020-69673-w. — View Citation
Ranjan AK, Briyal S, Khandekar D, Gulati A. Sovateltide (IRL-1620) affects neuronal progenitors and prevents cerebral tissue damage after ischemic stroke. Can J Physiol Pharmacol. 2020 Sep;98(9):659-666. doi: 10.1139/cjpp-2020-0164. Epub 2020 Jun 23. — View Citation
Ranjan AK, Gulati A. Sovateltide Mediated Endothelin B Receptors Agonism and Curbing Neurological Disorders. Int J Mol Sci. 2022 Mar 15;23(6):3146. doi: 10.3390/ijms23063146. — View Citation
* Note: There are 12 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | To determine the efficacy of sovateltide in patients with acute cerebral ischemic stroke assessed by modified Rankin Scale (mRS) score at day 90 post randomization | The proportion of acute cerebral ischemic stroke patients having a good outcome with modified Rankin Scale score of 0-2 on day 90 post randomization | Day 1 through Day 90 | |
Secondary | To determine excellent outcome of sovateltide in patients with acute cerebral ischemic stroke as assessed by modified Rankin Scale (mRS) score at day 90 post randomization | The proportion of acute cerebral ischemic stroke patients having an excellent functional outcome with modified Rankin Scale score of 0-1 on day 90 post randomization | Day 1 through Day 90 | |
Secondary | Increase in the proportion of acute cerebral ischemic stroke patients with National Institute of Health Stroke Scale (NIHSS) score < 6, mRS = 2, Barthel Index (BI) score > 60 on day 6, day 30, and day 90 post-randomization | Proportion of cerebral ischemic stroke patients with NIHSS score = 6, mRS > 2, and BI score = 60 on day 6, day 30, and day 90 post-randomization | Day 1 through Day 90 | |
Secondary | Improvement in the functional outcome of cerebral ischemic stroke patients as assessed by NIHSS, mRS, and BI scores at day 6, day 30, and day 90 post-randomization | Change in NIHSS score = 6, mRS score > 2, and BI score = 40 from baseline to day 6, day 30, and day 90 post-randomization | Day 1 through Day 90 | |
Secondary | Improvement in the overall clinical outcome as assessed by the global statistical test of mRS, NIHSS, and BI scores at day 6, day 30, and day 90 post-randomization. | Proportion of patients with overall clinical outcome as assessed by the global statistical test of NIHSS, mRS, and BI scores at day 6, day 30, and day 90 post-randomization | Day 1 through Day 90 | |
Secondary | Change in Quality-of-life (QoL) as assessed by EuroQol-EQ-5D and by Stroke-Specific Quality of Life (SSQOL) at day 30, day 60, and day 90 post- randomization | Change in QoL as assessed by EuroQol-EQ-5D and by SSQOL from baseline to day 30, day 60, and day 90 post-randomization | Day 1 through Day 90 | |
Secondary | Incidence of recurrent cerebral ischemic stroke within day 30 and day 90 post-randomization, as assessed by Questionnaire to Validate Stroke-Free Status (QVSFS) | Proportion of patients with recurrent ischemic stroke within day 30 and day 90 post-randomization as assessed by Questionnaire to Validate Stroke-Free Status (QVSFS) | Day 1 through Day 90 | |
Secondary | Incidence of mortality within 90 days post-randomization | Number of deaths within day 90 post-randomization | Day 1 through Day 90 | |
Secondary | Incidence of radiographic or symptomatic Intra Cerebral Hemorrhage (ICH) within 24 (± 6) hours of randomization | Proportion of patients with radiographic or symptomatic ICH within 24 (± 6) hours of randomization | Day 1 through Day 90 | |
Secondary | Any adverse events (AE) or serious adverse events (SAEs) are associated with sovateltide | Proportion of patients with adverse events (AEs) and serious adverse events (SAEs) | Day 1 through Day 90 |
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