Back to resultsEfficacy of Sovateltide (PMZ-1620) in Patients of Acute Ischemic Stroke
Primary Purpose
Cerebral Ischemia, Cerebral Infarction, Stroke, Acute
Status
Completed
Phase
Phase 3
Locations
India
Study Type
Interventional
Intervention
Normal Saline along with standard treatment
PMZ-1620 (sovateltide) along with standard treatment
Sponsored by
About this trial
This is an interventional treatment trial for Cerebral Ischemia focused on measuring Endothelin, Neurogenesis, Neural progenitor cells
Eligibility Criteria
Inclusion Criteria:
- Adult males or females Aged 18 years through 78 years (have not had their 79th birthday).
- Patient or Legally Authorized Representative willing to give informed Consent before study procedure.
- 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.
- 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.
- 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.
- Reasonable expectation of availability to receive the full PMZ-1620 course of therapy, and to be available for subsequent follow-up visits.
Exclusion Criteria:
- 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.
- 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).
- Evidence of intracranial hemorrhage (intracerebral hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, epidural hemorrhage, acute or chronic subdural hematoma on the baseline CT or MRI scan.
- Known pregnancy.
- Confounding pre-existing neurological or psychiatric disease.
- Concurrent participation in any other therapeutic clinical trial.
- 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.
Sites / Locations
- Pushpanjali Hospital & Research Centre Pvt. Ltd
- Radiant Superspeciality Hospital
- Post Graduate Institute of Medical Education and Research
- Lalitha Superspecialities Hospital
- Dayanand Medical College & Hospital
- Department of Neurology, Christian Medical College and Hospital
- Sidhu Hospital Pvt. Ltd.
- New Era Hospital & Research Institute
- Chopda Medicare & Research Centre
- All India Institute of Medical Sciences
- Indian Spinal Injury Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Normal Saline + Standard of care
PMZ-1620 (sovateltide) + Standard of care
Arm Description
Patients will receive the best available standard of care. In control group, 3 doses of equal volume of normal saline will be administered as an IV bolus over 1 minutes every 3 hours ± 1 hour on day 1, 3 and day 6 post randomization.
Patients will receive the best available standard of care. In PMZ group, 3 doses of PMZ-1620, at 0.3 μg/kg body weight will be administered as an intravenous bolus over 1 minute every 3 hours ± 1 hour on day 1, 3, and day 6 (total dose/day: 0.9 µg/kg body weight).
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
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.
Secondary Outcome Measures
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.
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.
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
Incidence of mortality
Incidence of mortality within 3 months post-randomization
Incidence of Intra-Cerebral Hemorrhage (ICH)
Incidence of symptomatic Intra Cerebral Hemorrhage (ICH) within 24 (± 6) hours of randomization
Incidence of PMZ-1620 related adverse events
Another objective of the study is to determine incidence of drug (PMZ-1620) related adverse events.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04047563
Brief Title
Efficacy of Sovateltide (PMZ-1620) in Patients of Acute Ischemic Stroke
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
November 10, 2019 (Actual)
Primary Completion Date
February 10, 2022 (Actual)
Study Completion Date
February 10, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmazz, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cerebral Ischemia, Cerebral Infarction, Stroke, Acute
Keywords
Endothelin, Neurogenesis, Neural progenitor cells
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
In PMZ group, 3 doses of PMZ-1620, at 0.3 μg/kg body weight will be administered as an intravenous bolus over 1 minute every 3 hours ± 1 hour on day 1, 3, and day 6 (total dose/day: 0.9 µg/kg body weight).
In control group, 3 doses of equal volume of normal saline will be administered as an IV bolus over 1 minutes every 3 hours ± 1 hour on day 1, 3 and day 6 post randomization.
In both treatment groups, subjects will be provided the best available standard of care.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
158 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Normal Saline + Standard of care
Arm Type
Active Comparator
Arm Description
Patients will receive the best available standard of care. In control group, 3 doses of equal volume of normal saline will be administered as an IV bolus over 1 minutes every 3 hours ± 1 hour on day 1, 3 and day 6 post randomization.
Arm Title
PMZ-1620 (sovateltide) + Standard of care
Arm Type
Experimental
Arm Description
Patients will receive the best available standard of care. In PMZ group, 3 doses of PMZ-1620, at 0.3 μg/kg body weight will be administered as an intravenous bolus over 1 minute every 3 hours ± 1 hour on day 1, 3, and day 6 (total dose/day: 0.9 µg/kg body weight).
Intervention Type
Drug
Intervention Name(s)
Normal Saline along with standard treatment
Other Intervention Name(s)
Vehicle
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
PMZ-1620 (sovateltide) along with standard treatment
Other Intervention Name(s)
PMZ-1620
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in National Institute of Health Stroke Scale (NIHSS)
Description
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.
Time Frame
90 days
Title
Change in modified Rankin Scale (mRS)
Description
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.
Time Frame
90 days
Title
Change in Barthel index [BI]
Description
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.
Time Frame
90 days
Title
Change in the proportion of ischemic stroke patients with NIHSS score <6
Description
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.
Time Frame
90 days
Title
Change in the proportion of ischemic stroke patients with mRS score <2
Description
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.
Time Frame
90 days
Title
Change in the proportion of ischemic stroke patients with Barthel index (BI) score >60
Description
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.
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Change in Quality-of-life as assessed by EuroQol-EQ-5D
Description
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.
Time Frame
90 days
Title
Change in Stroke-Specific Quality of Life (SSQOL)
Description
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.
Time Frame
90 days
Title
Incidence in recurrence of ischemic stroke
Description
Incidence of recurrent ischemic stroke within 1 month and 3 months post-randomization, as assessed by Questionnaire to Validate Stroke-Free Status
Time Frame
90 days
Title
Incidence of mortality
Description
Incidence of mortality within 3 months post-randomization
Time Frame
90 days
Title
Incidence of Intra-Cerebral Hemorrhage (ICH)
Description
Incidence of symptomatic Intra Cerebral Hemorrhage (ICH) within 24 (± 6) hours of randomization
Time Frame
30 hours
Title
Incidence of PMZ-1620 related adverse events
Description
Another objective of the study is to determine incidence of drug (PMZ-1620) related adverse events.
Time Frame
90 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
78 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult males or females Aged 18 years through 78 years (have not had their 79th birthday).
Patient or Legally Authorized Representative willing to give informed Consent before study procedure.
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.
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.
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.
Reasonable expectation of availability to receive the full PMZ-1620 course of therapy, and to be available for subsequent follow-up visits.
Exclusion Criteria:
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.
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).
Evidence of intracranial hemorrhage (intracerebral hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, epidural hemorrhage, acute or chronic subdural hematoma on the baseline CT or MRI scan.
Known pregnancy.
Confounding pre-existing neurological or psychiatric disease.
Concurrent participation in any other therapeutic clinical trial.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anil Gulati, MD, PhD
Organizational Affiliation
Chairman and CEO
Official's Role
Study Chair
Facility Information:
Facility Name
Pushpanjali Hospital & Research Centre Pvt. Ltd
City
Agra
State/Province
Uttar Pradesh
ZIP/Postal Code
282002
Country
India
Facility Name
Radiant Superspeciality Hospital
City
Amravati
ZIP/Postal Code
444606
Country
India
Facility Name
Post Graduate Institute of Medical Education and Research
City
Chandigarh
ZIP/Postal Code
160012
Country
India
Facility Name
Lalitha Superspecialities Hospital
City
Guntur
ZIP/Postal Code
522001
Country
India
Facility Name
Dayanand Medical College & Hospital
City
Ludhiana
ZIP/Postal Code
141001
Country
India
Facility Name
Department of Neurology, Christian Medical College and Hospital
City
Ludhiana
ZIP/Postal Code
141008
Country
India
Facility Name
Sidhu Hospital Pvt. Ltd.
City
Ludhiana
ZIP/Postal Code
141421
Country
India
Facility Name
New Era Hospital & Research Institute
City
Nagpur
ZIP/Postal Code
440008
Country
India
Facility Name
Chopda Medicare & Research Centre
City
Nashik
ZIP/Postal Code
422005
Country
India
Facility Name
All India Institute of Medical Sciences
City
New Delhi
ZIP/Postal Code
110029
Country
India
Facility Name
Indian Spinal Injury Centre
City
New Delhi
ZIP/Postal Code
110070
Country
India
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Results will be communicated and published as manuscript
Citations:
PubMed Identifier
31320660
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.
Results Reference
background
PubMed Identifier
30406063
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.
Results Reference
background
PubMed Identifier
29947531
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.
Results Reference
background
PubMed Identifier
26398673
Citation
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.
Results Reference
background
PubMed Identifier
23850649
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.
Results Reference
background
PubMed Identifier
22580085
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.
Results Reference
background
PubMed Identifier
21959172
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.
Results Reference
background
PubMed Identifier
32728189
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.
Results Reference
background
PubMed Identifier
32574518
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.
Results Reference
background
PubMed Identifier
33428177
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):85-104. doi: 10.1007/s40263-020-00783-9. Epub 2021 Jan 11.
Results Reference
result
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Efficacy of Sovateltide (PMZ-1620) in Patients of Acute Ischemic Stroke
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