Efficacy of Sovateltide (PMZ-1620) in Patients of Acute Ischemic Stroke

Stroke, Acute Clinical Trial

Official title:

A Prospective, Multicentric, Randomized, Double-blind, Parallel, Phase III Clinical Study to Assess Efficacy of PMZ-1620 Along With Standard Treatment in Patients of Acute Ischemic Stroke

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04047563
• Other study ID #: PMZ-1620/CT-3.1/2019
• Status: Completed
• Phase: Phase 3
• Start date: November 10, 2019
• Est. completion date: February 10, 2022

Study information

• Verified date: October 2023
• Source: Pharmazz, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In the present prospective, multicentric, randomized, double-blind, parallel, saline-controlled phase II clinical study; the investigators plan to evaluate the efficacy of sovateltide (IRL-1620 or PMZ-1620) therapy along with standard supportive care in patients of acute ischemic stroke.

Description:

The peptide Sovateltide (IRL-1620) is a highly selective ETB receptor agonist. There are hidden stem cells in the brain, which becomes active following injury to the brain. Intravenous administration of PMZ-1620 (sovateltide) augments the activity of neuronal progenitor cells in the brain to repair the damage by formation of new mature neurons and blood vessels. In addition, PMZ-1620 has anti-apoptotic activity and also increases cerebral blood flow when administered following ischemia. It was discovered that in rat model of ischemic stroke, sovateltide, significantly improved survival, reduces neurological and motor function deficit while effectively decreasing infarct volume, edema and oxidative stress. The convincing results of preclinical efficacy studies of Sovateltide in ischemic stroke and its safety affirmation from phase I and phase II clinical studies encouraged us to investigate its efficacy in human patients of ischemic stroke. In the present prospective, multicentric, randomized, double-blind, parallel, saline-controlled phase II clinical study; the investigators plan to evaluate the efficacy of Sovateltide therapy along with standard supportive care in patients of acute ischemic stroke.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 158
• Est. completion date: February 10, 2022
• Est. primary completion date: February 10, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 78 Years

Eligibility

Inclusion Criteria:

1. Adult males or females Aged 18 years through 78 years (have not had their 79th birthday).

2. Patient or Legally Authorized Representative 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 upto 24 hours after onset of symptoms with mRS score of 3-4 (pre-stroke mRS score of 0 or 1) and NIHSS score >5 (NIHSS Level of Consciousness (1A) score must be < 2). This also includes patients who had ischemic stroke in the past and are completely recovered from earlier episode before having new or fresh stroke.

5. Patient is < 24 hours from time of stroke onset when the first dose of PMZ-1620 therapy is administered. Time of onset is when symptoms began; for stroke that occurred during sleep, time of onset is when patient was last seen or was self- reported to be normal.

6. Reasonable expectation of availability to receive the full PMZ-1620 course of therapy, and to be available for subsequent follow-up visits.

Exclusion Criteria:

1. Patients receiving endovascular therapy or is a candidate for any surgical intervention for treatment of stroke which may include but not limited to endovascular techniques.

2. Patients classified as comatose, defined as a patient who required 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, epidural hemorrhage, acute or chronic subdural hematoma on the baseline CT or MRI scan.

4. Known pregnancy.

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 PMZ-1620 therapy would be contraindicated or might cause harm to the patient.

Related Conditions & MeSH terms

• Brain Ischemia
• Cerebral Infarction
• Cerebral Ischemia
• Infarction
• Ischemia
• Ischemic Stroke
• Stroke
• Stroke, Acute

Intervention

Drug:
• Normal Saline along with standard treatment
PMZ-1620 (sovateltide) is an endothelin-B receptor agonist. PMZ-1620 has the potential to be a first-in-class neuronal progenitor cell therapeutics that is likely to promote quicker recovery and improve neurological outcome in cerebral ischemic stroke patients. In this arm normal saline along with standard treatment will be given for active comparison.
• PMZ-1620 (sovateltide) along with standard treatment
PMZ-1620 (sovateltide) is an endothelin-B receptor agonist. PMZ-1620 has the potential to be a first-in-class neuronal progenitor cell therapeutics that is likely to promote quicker recovery and improve neurological outcome in cerebral ischemic stroke patients.

Locations

Country	Name	City	State
India	Pushpanjali Hospital & Research Centre Pvt. Ltd	Agra	Uttar Pradesh
India	Radiant Superspeciality Hospital	Amravati
India	Post Graduate Institute of Medical Education and Research	Chandigarh
India	Lalitha Superspecialities Hospital	Guntur
India	Dayanand Medical College & Hospital	Ludhiana
India	Department of Neurology, Christian Medical College and Hospital	Ludhiana
India	Sidhu Hospital Pvt. Ltd.	Ludhiana
India	New Era Hospital & Research Institute	Nagpur
India	Chopda Medicare & Research Centre	Nashik
India	All India Institute of Medical Sciences	New Delhi
India	Indian Spinal Injury Centre	New Delhi

Sponsors (1)

Lead Sponsor	Collaborator
Pharmazz, Inc.

Country where clinical trial is conducted

India, 

References & Publications (10)

Bhalla S, Leonard MG, Briyal S, Gulati A. Distinct Alteration in Brain Endothelin A and B Receptor Characteristics Following Focal Cerebral Ischemia in Rats. Drug Res (Stuttg). 2016 Apr;66(4):189-95. doi: 10.1055/s-0035-1559779. Epub 2015 Sep 23. — View Citation

Briyal S, Ranjan AK, Hornick MG, Puppala AK, Luu T, Gulati A. Anti-apoptotic activity of ETB receptor agonist, IRL-1620, protects neural cells in rats with cerebral ischemia. Sci Rep. 2019 Jul 18;9(1):10439. doi: 10.1038/s41598-019-46203-x. Erratum In: Sci Rep. 2020 Feb 14;10(1):2992. — View Citation

Cifuentes EG, Hornick MG, Havalad S, Donovan RL, Gulati A. Neuroprotective Effect of IRL-1620, an Endothelin B Receptor Agonist, on a Pediatric Rat Model of Middle Cerebral Artery Occlusion. Front Pediatr. 2018 Oct 23;6:310. doi: 10.3389/fped.2018.00310. eCollection 2018. — 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

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in National Institute of Health Stroke Scale (NIHSS)	Neurological outcome as assessed by National Institute of Health Stroke Scale (NIHSS) score post randomization. NIHSS is 42 point scale where 0 is the best and 42 is the worst outcome.	90 days
Primary	Change in modified Rankin Scale (mRS)	Neurological outcome as assessed by modified Rankin Scale (mRS) score post randomization. mRS is a 7 grade scale from 0 to 6, where 0 is the best and 6 is the worst outcome.	90 days
Primary	Change in Barthel index [BI]	Overall clinical outcome as assessed by Barthel index [BI] scores) at 3 months post randomization. BI is a 10 item scale with scores ranging from 0 to 100, where a score of 100 is the best and 0 is the worst outcome.	90 days
Primary	Change in the proportion of ischemic stroke patients with NIHSS score <6	Change in the proportion of ischemic stroke patients with National Institute of Health Stroke Scale (NIHSS) score <6 at day 6, 1 month and 3 months. NIHSS is 42 point scale where 0 is the best and 42 is the worst outcome.	90 days
Primary	Change in the proportion of ischemic stroke patients with mRS score <2	Change in the proportion of ischemic stroke patients with modified Rankin Scale (mRS) score <2 at day 6, 1 month and 3 months. mRS is a 7 grade scale from 0 to 6, where 0 is the best and 6 is the worst outcome.	90 days
Primary	Change in the proportion of ischemic stroke patients with Barthel index (BI) score >60	Change in the proportion of ischemic stroke patients with Barthel index (BI) score >60 at day 6, 1 month and 3 months. BI is a 10 item scale with scores ranging from 0 to 100, where a score of 100 is the best and 0 is the worst outcome.	90 days
Secondary	Change in Quality-of-life as assessed by EuroQol-EQ-5D	Quality-of-life as assessed by EuroQol-EQ-5D will be determined at 1 month and 3 months post randomization. EuroQol-EQ-5D is a concise, generic instrument that could be used to measure, compare and value health status across disease areas. It is a five dimension instrument with scores ranging from 0 to 100, where a score of 100 is the best and 0 is the worst outcome.	90 days
Secondary	Change in Stroke-Specific Quality of Life (SSQOL)	Stroke-Specific Quality of Life (SSQOL) will be assessed at 1 month and 3 months post randomization. SSQOL is composed of 49 items with scores ranging from 49 to 245, where a score of 245 is the best and 49 is the worst outcome.	90 days
Secondary	Incidence in recurrence of ischemic stroke	Incidence of recurrent ischemic stroke within 1 month and 3 months post-randomization, as assessed by Questionnaire to Validate Stroke-Free Status	90 days
Secondary	Incidence of mortality	Incidence of mortality within 3 months post-randomization	90 days
Secondary	Incidence of Intra-Cerebral Hemorrhage (ICH)	Incidence of symptomatic Intra Cerebral Hemorrhage (ICH) within 24 (± 6) hours of randomization	30 hours
Secondary	Incidence of PMZ-1620 related adverse events	Another objective of the study is to determine incidence of drug (PMZ-1620) related adverse events.	90 days