PMZ-1620 (Sovateltide) in Acute Ischemic Stroke Patients

NCT04046484 | Completed Phase 2 DMC

• 2 other identifiers: PMZ-01 Version 2.0/18CTRI/2017/11/010654
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 7

Brief Summary

This was a prospective, multicentric, randomized, double blind, parallel, saline controlled Phase II clinical study to compare the safety and efficacy of PMZ-1620 (INN: Sovateltide) therapy along with standard supportive care in patients of acute ischemic stroke.

Conditions

Acute Stroke; Cerebral Ischemia

Outcome Measures

Primary Outcomes (2)

• Incidence of PMZ-1620 related adverse events

  The primary objective of the study is to determine incidence of drug (PMZ-1620) related adverse events.

  90 days

• Number of patients not receiving full treatment

  Tolerability will be determined by the number of patients that do not receive all the 9 doses of PMZ-1620.

  90 days

Secondary Outcomes (8)

• Change in National Institute of Health Stroke Scale (NIHSS)

  90 days

• Change in modified Rankin Scale (mRS)

  90 days

• Change in Barthel index [BI]

  90 days

• Change in EuroQol

  90 days

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

  90 days

Study Arms (2)

Normal Saline (Dose: Equal volume) + 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 + 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 along with standard treatment

Interventions

Normal Saline along with standard treatment DRUG

The arm is for active comparison for PMZ-1620 (sovateltide), 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. Normal saline (vehicle) with standard treatment will be provided.

Also known as: Vehicle

Normal Saline (Dose: Equal volume) + Standard of care

PMZ-1620 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: Sovateltide (IRL-1620) along with standard treatment

PMZ-1620 + Standard of care

Eligibility Criteria

• Age: 18 Years - 70 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 70 years (have not had their 71st birthday)
• Signed and dated informed Consent from Legally Acceptable Representative, if subject is not in the condition to give consent. However, when the subject is stable and is able to give consent, consent would be obtained on a separate informed consent form to confirm his/her willingness to continue in the study
• Stroke is ischemic in origin, supratentorial, and radiologically confirmed Computed Tomography (CT) scan or diagnostic magnetic resonance imaging (MRI) prior to enrolment
• New (first time) cerebral ischemic strokes subjects presenting upto 24 hours after onset of symptoms (mRS score of 3-4) with a prestroke mRS score of 0 or 1 and NIHSS score of 5-14)
• No hemorrhage as proved by cerebral CT/MRI scan
• Subject 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 subject 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
• Subjects receiving thrombolytic therapy
• Reasonable expectation that subject will receive standard post- stroke physical, occupational, speech, and cognitive therapy as indicated
• Female subject is either:
• Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) or,
• If of childbearing potential, agrees to use any of the following effective separate forms of contraception throughout the study, up to and including the follow-up visits: Condoms, sponge, foams, jellies, diaphragm or intrauterine device, OR A vasectomised partner OR abstinence

You may not qualify if:

• Subjects receiving endovascular therapy
• Subjects presenting with lacunar, hemorrhagic and/or brain stem stroke
• Subjects classified as comatose, defined as a subject who required repeated stimulation to attend, or is obtunded and requires strong or painful stimulation to make movements (NIHSS Level of Consciousness (1A) score must be \< 2)
• Episode/exacerbation of congestive heart failure (CHF) from any cause in the last 6 months. (An episode of CHF is any heart failure that required a change in medication, change in diet or hospitalization)
• 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
• Known valvular heart disease with CHF in the last 6 months
• Known (or in the Investigator's clinical judgment) existence of severe aortic stenosis or mitral stenosis
• Cardiac surgery involving thoracotomy (e.g., coronary artery bypass graft, (CABG), valve replacement surgery) in the last 6 months
• Subject is a candidate for any surgical intervention for treatment of stroke which may include but not limited to endovascular techniques
• Subjects who are obese, body mass index (BMI) \> 30 and/or on hormonal contraceptives
• Hypo- or hyperglycemia sufficient to account for the neurological symptoms; patient should be excluded if their blood glucose is \< 3.0 or \> 20.0 mmol/L
• Patient has systolic BP \< 90 mmHg or \> 220 mmHg or diastolic BP \< 40 mmHg or \> 130 mmHg
• Acute myocardial infarction in the last 6 months
• Signs or symptoms of acute myocardial infarction, including electrocardiogram findings, on admission
• Concomitant treatment with neuroprotective or nootropic drugs (e.g. piracetam, citicoline, investigational, neuroprotecti-ve substances)

Sponsors & Collaborators

• Pharmazz, Inc.: lead

Study Sites (7)

Paras Hospital

Gūrgaon, 122002, India

Location

Nizam's Institute of Medical Sciences

Hyderabad, 500082, India

Location

Sanjay Gandhi Post Graduate Institute of Medical Sciences

Lucknow, 226014, India

Location

Dayanand Medical College & Hospital

Ludhiana, 141001, India

Location

Department of Neurology, Christian Medical College and Hospital

Ludhiana, 141008, India

Location

New Era Hospital & Research Institute

Nagpur, 440008, India

Location

All India Institute of Medical Sciences

New Delhi, 110029, India

Location

Related Publications (10)

• 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, 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

• 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

• 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

• 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

MeSH Terms

Conditions

Stroke; Brain Ischemia

Interventions

sovateltide

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Anil Gulati

  Pharmazz, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: July 31, 2019
• First Posted: August 6, 2019
• Study Start: January 19, 2018
• Primary Completion: April 12, 2019
• Study Completion: June 30, 2019
• Last Updated: May 12, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

IN (7)