Assess the Safety and Efficacy of Sovateltide in Patients With Acute Cerebral Ischemic Stroke

NCT05691244 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: Sovateltide/ACIS/IND2022
• Study Type: interventional
• Target: 514
• Locations: 4 countries
• Sites: 42

Brief Summary

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.

Conditions

Acute Ischemic Stroke; Cerebral Stroke

Keywords

Endothelin B Receptors

Outcome Measures

Primary Outcomes (1)

• Determine the efficacy of sovateltide in patients with acute cerebral ischemic stroke assessed by modified Rankin Scale (mRS) score of 0-2 at day 90 post-randomization.

  The proportion of acute cerebral ischemic stroke patients having a good functional outcome with a modified Rankin Scale score of 0-2 on day 90 post-randomization.

  Day 1 through Day 90

Secondary Outcomes (10)

• Determine a good functional outcome in patients with acute cerebral ischemic stroke assessed by the National Institute of Health Stroke Scale (NIHSS) score of <6 at day 90 post-randomization.

  Day 1 through Day 90

• Determine a good functional outcome in patients with acute cerebral ischemic stroke assessed by the Barthel Index (BI) score of ≥90 at day 90 post-randomization.

  Day 1 through Day 90

• Determine an excellent functional outcome in patients with acute cerebral ischemic stroke assessed by a modified Rankin Scale score of 0-1 at day 90 post-randomization.

  Day 1 through Day 90

• Determine a change in Quality-of-life (QoL) as assessed by EuroQol-EQ-5D-5L and Stroke-Specific Quality of Life (SS-QOL) at days 30, 60, and 90 post-randomization.

  Day 1 through Day 90

• Determine the incidence of recurrent cerebral ischemic stroke within 90 days post-randomization.

  Day 1 through Day 90

Other Outcomes (5)

• Determine a good functional outcome in patients with acute cerebral ischemic stroke assessed by mRS score of 0-2 at day 30 post-randomization.

  Day 1 through Day 30

• Determine a good functional outcome in patients with acute cerebral ischemic stroke assessed by the NIHSS score of <6 at day 30 post-randomization.

  Day 1 through Day 30

• Determine a good functional outcome in patients with acute cerebral ischemic stroke assessed by the BI score of ≥90 at day 30 post-randomization.

  Day 1 through Day 30

Study Arms (2)

Normal Saline + Standard of care

ACTIVE COMPARATOR

Normal saline will be used as a comparator. It will be available in a 5.0 mL vial. Three doses will be administered as an IV bolus over one minute every 3 hours ± 1 hour on day 1. The dose will be repeated on days 3 and 6 post randomization. The study drug will be administered as an IV bolus dose over 1 minute within 24 hours of the stroke onset.

Drug: Drug: Normal Saline

Sovateltide + Standard of care

EXPERIMENTAL

The test product is sovateltide. It is available as a lyophilized injection containing 30 µg of sovateltide in a 5.0 mL vial. Three doses of 0.3 μg/kg will be administered as an IV bolus over one minute every 3 hours ± 1 hour on day 1. The dose will be repeated on days 3 and 6 post randomization. The study drug will be administered as an IV bolus dose over 1 minute within 24 hours of the stroke onset.

Drug: Sovateltide

Interventions

Drug: Normal Saline DRUG

Normal saline to be used as vehicle in the phase-III study to assess efficacy of sovateltide in patients with acute cerebral ischemic stroke.

Also known as: Vehicle

Normal Saline + Standard of care

Sovateltide DRUG

Phase-III study to assess efficacy of sovateltide in patients with acute cerebral ischemic stroke.

Also known as: PMZ-1620

Sovateltide + Standard of care

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males or females aged 18 - 80 years of age.
• Consent obtained per national laws and regulations, and in accordance with the applicable ethics committee requirements prior to study procedures.
• A stroke is ischemic in origin that is diagnosed clinically and/or radiologically confirmed by 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 within 24 hours after the onset of symptoms with NIHSS score of ≥8 and \<20, 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 having a pre-stroke historical measure of mRS score of 0-2.
• The patient is \<24 hours from the 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.
• Reasonable expectation of availability to receive the full sovateltide/placebo 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 the treatment of stroke, which may include but not limited to endovascular techniques.
• 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).
• 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 pregnancy and lactating women.
• Known medical history of neurological (other than current acute ischemic stroke) or psychiatric condition that, in the investigator's opinion, would confound the neurological and functional evaluations, lead to further deterioration of neurological status, or interfere with participation in this study.
• 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 sovateltide therapy would be contraindicated or might cause harm to the patient.

Sponsors & Collaborators

• Pharmazz, Inc.: lead

Study Sites (42)

The University of Arizona - College of Medicine

Tuscon, Arizona, 85719, United States

RECRUITING

Mercy Medical Group

Carmichael, California, 95608, United States

RECRUITING

St. John's Regional Medical Center

Oxnard, California, 93030, United States

RECRUITING

SSM Health Neurosciences

Bridgeton, Missouri, 63044, United States

RECRUITING

OSU Wexner Medical Center

Columbus, Ohio, 43210, United States

RECRUITING

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

CHI Memorial Neuroscience Institute

Chattanooga, Tennessee, 37404, United States

RECRUITING

Houston Medical Neurological Institute

Houston, Texas, 77030, United States

RECRUITING

Memorial Hermann Hospital

Houston, Texas, 77030, United States

RECRUITING

Klinikum Altenburger Land GmbH

Altenburg, Altenburg, 04600, Germany

RECRUITING

Universitaetsklinikum Goettingen

Göttingen, Lower Saxony, 37075, Germany

RECRUITING

Klinikum der Stadt Ludwigshafen gGmbh

Rhein, Ludwigshafen Am, 67063, Germany

RECRUITING

Muhlenkreiskliniken (MKK) - Johannes Wesling Klinikum Minden - Neurologische Klinik

Minden, North Rhine-Westphalia, 32427, Germany

RECRUITING

Klinik fuer Neurologie, Stroke Unit und Fruehrehabilitation Dorstener Strae 151

Recklinghausen, Recklinghausen, 45657, Germany

RECRUITING

Charite-Universitaetsmedizin Berlin

Berlin, State of Berlin, 12203, Germany

RECRUITING

Universitätsklinikum Essen AöR

Essen, 45147, Germany

RECRUITING

Universitätsklinikum Schleswig-Holstein AöR

Lübeck, 23538, Germany

RECRUITING

Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona, 08035, Spain

RECRUITING

Complejo Hospitalario Universitario de Albacete

Albacete, Castille-La Mancha, 2006, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

RECRUITING

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, Madrid, 28222, Spain

RECRUITING

Hospital Clínico Universitario Virgen de Arrixaca

El Palmar, Murcia, 30120, Spain

RECRUITING

Hospital Universitario Virgen Macarena

Seville, Sevilla, 41009, Spain

RECRUITING

Hospital Universitari Joan XXIII

Tarragona, Tarragona, 43005, Spain

RECRUITING

Instituto de Investigación Biomédica de A Coruña

A Coruña, 15006, Spain

RECRUITING

Hospital Universitario Infanta Cristina (HUB)

Badajoz, 06080, Spain

RECRUITING

Hospital Universitario de Cruces

Barakaldo, 48903, Spain

RECRUITING

Institut Catala d'Oncologia (ICO) - Hospital Universitari Doctor Josep Trueta

Girona, 17007, Spain

RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Clinico San Carlos

Madrid, 28040, Spain

RECRUITING

Hospital Clinico Universitario de Santiago

Santiago, 15706, Spain

RECRUITING

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

RECRUITING

Fairfield General Hospital

Bury, Bury, BL9 7TD, United Kingdom

RECRUITING

National Hospital for Neurology & Neurosurgery

London, London, NW1 2BU, United Kingdom

RECRUITING

King's College Hospital NHS Foundation Trust

London, London, SE5 9RS, United Kingdom

RECRUITING

University Hospital Southampton

Southampton, Southampton, SO16 6YD, United Kingdom

RECRUITING

New Cross Hospital - Royal Wolverhampton NHS Trust

Wolverhampton, Wolverhampton, WV10 0QP, United Kingdom

RECRUITING

Hospitals NHS Foundation Trust - Royal Victoria Infirmary RVI

Newcastle, NE1 4LP, United Kingdom

RECRUITING

Related Publications (15)

• 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 BACKGROUND

• 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.

  PMID: 35328566 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 BACKGROUND

• 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.

  PMID: 34826534 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, 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

• 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.

  PMID: 26022359 BACKGROUND

• 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.

  PMID: 25806822 BACKGROUND

• 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.

  PMID: 24561065 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

• Keam SJ. Sovateltide: First Approval. Drugs. 2023 Sep;83(13):1239-1244. doi: 10.1007/s40265-023-01922-4.

  PMID: 37486545 BACKGROUND

• Briyal S, Ranjan AK, Gulati A. Oxidative stress: A target to treat Alzheimer's disease and stroke. Neurochem Int. 2023 May;165:105509. doi: 10.1016/j.neuint.2023.105509. Epub 2023 Mar 11.

  PMID: 36907516 BACKGROUND

MeSH Terms

Conditions

Ischemic Stroke; Stroke

Interventions

Saline Solution; sovateltide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Anil Gulati, MD, PhD

  Pharmazz, Inc.

  STUDY CHAIR

Central Study Contacts

Anil Gulati, MD, PhD

CONTACT

6307806087; anil.gulati@pharmazz.com

Neil Marwah, MD

CONTACT

6307806087; neil.marwah@pharmazz.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: In this double-blind study, the subject and all relevant personnel involved with the conduct and interpretation of the study (including investigator, investigational site personnel, and the sponsor or designee's staff) will remain blinded to the identity of the Investigational Product (IP) assigned and the randomization codes. The final randomization list will be kept strictly confidential, filed securely by the independent biostatistician, and accessible only to authorized persons as per the sponsor's standard operating procedures until the completion of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a multi-centric, randomized, double-blind, placebo-controlled phase-III clinical study to assess the safety and efficacy of sovateltide in patients with acute cerebral ischemic stroke.

Study Record Dates

• First Submitted: January 11, 2023
• First Posted: January 19, 2023
• Study Start: July 24, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: December 2027
• Access Criteria: Following completion of the trial in 2027, the anonymized patient datasets created and/or analyzed for the current study can be accessed from the corresponding author at a reasonable request from a bona fide researcher/research group.

Locations

US (9); DE (8); ES (19); GB (6)