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

NCT04047563 | Completed Phase 3 DMC

• 1 other identifier: PMZ-1620/CT-3.1/2019
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 11

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.

Conditions

Cerebral Ischemia; Cerebral Infarction; Stroke, Acute

Keywords

Endothelin; Neurogenesis; Neural progenitor cells

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (6)

• Change in Quality-of-life as assessed by EuroQol-EQ-5D

  90 days

• Change in Stroke-Specific Quality of Life (SSQOL)

  90 days

• Incidence in recurrence of ischemic stroke

  90 days

• Incidence of mortality

  90 days

• Incidence of Intra-Cerebral Hemorrhage (ICH)

  30 hours

Study Arms (2)

Normal Saline + Standard of care

ACTIVE COMPARATOR

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.

Drug: Normal Saline along with standard treatment

PMZ-1620 (sovateltide) + Standard of care

EXPERIMENTAL

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).

Drug: PMZ-1620 (sovateltide) along with standard treatment

Interventions

Normal Saline along with standard treatment DRUG

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.

Also known as: Vehicle

Normal Saline + Standard of care

PMZ-1620 (sovateltide) along with standard treatment DRUG

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.

Also known as: PMZ-1620

PMZ-1620 (sovateltide) + Standard of care

Eligibility Criteria

• Age: 18 Years - 78 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pharmazz, Inc.: lead

Study Sites (11)

Pushpanjali Hospital & Research Centre Pvt. Ltd

Agra, Uttar Pradesh, 282002, India

Location

Radiant Superspeciality Hospital

Amravati, 444606, India

Location

Post Graduate Institute of Medical Education and Research

Chandigarh, 160012, India

Location

Lalitha Superspecialities Hospital

Guntur, 522001, India

Location

Dayanand Medical College & Hospital

Ludhiana, 141001, India

Location

Department of Neurology, Christian Medical College and Hospital

Ludhiana, 141008, India

Location

Sidhu Hospital Pvt. Ltd.

Ludhiana, 141421, India

Location

New Era Hospital & Research Institute

Nagpur, 440008, India

Location

Chopda Medicare & Research Centre

Nashik, 422005, India

Location

All India Institute of Medical Sciences

New Delhi, 110029, India

Location

Indian Spinal Injury Centre

New Delhi, 110070, India

Location

Related Publications (11)

• 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.

  PMID: 31320660 BACKGROUND

• 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.

  PMID: 30406063 BACKGROUND

• 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.

  PMID: 29947531 BACKGROUND

• 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.

  PMID: 26398673 BACKGROUND

• 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.

  PMID: 23850649 BACKGROUND

• 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.

  PMID: 22580085 BACKGROUND

• 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.

  PMID: 21959172 BACKGROUND

• 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.

  PMID: 32728189 BACKGROUND

• 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.

  PMID: 32574518 BACKGROUND

• 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.

  PMID: 33428177 RESULT

• Gulati A, Adwani SG, Vijaya P, Agrawal NR, Ramakrishnan TCR, Rai HP, Jain D, Sundarachary NV, Pandian JD, Sardana V, Sharma M, Sidhu GK, Anand SS, Vibha D, Aralikatte S, Khurana D, Joshi D, Karadan U, Siddiqui MSI. Efficacy and Safety of Sovateltide in Patients with Acute Cerebral Ischaemic Stroke: A Randomised, Double-Blind, Placebo-Controlled, Multicentre, Phase III Clinical Trial. Drugs. 2024 Dec;84(12):1637-1650. doi: 10.1007/s40265-024-02121-5. Epub 2024 Nov 15.

  PMID: 39542995 DERIVED

MeSH Terms

Conditions

Brain Ischemia; Cerebral Infarction; Stroke

Interventions

sovateltide

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Infarction; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Study Officials

• Anil Gulati, MD, PhD

  Chairman and CEO

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 5, 2019
• First Posted: August 6, 2019
• Study Start: November 10, 2019
• Primary Completion: February 10, 2022
• Study Completion: February 10, 2022
• Last Updated: October 18, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

IN (11)