Acute Ischemic StrokePhase 3RESPECT-ETBNCT05691244
Assess the Safety and Efficacy of Sovateltide in Patients With Acute Cerebral Ischemic Stroke
A Phase 3 study testing Drug: Normal Saline and Sovateltide in people with Acute Ischemic Stroke and Cerebral Stroke, run by Pharmazz, Inc. at 54 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acute Ischemic Stroke, Cerebral Stroke
- What is being tested?
- Drug: Normal Saline and Sovateltide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 514 participants
- Where
- 54 sitesin 4 countries
- Study dates
- 24 Jul 2025to Dec 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A patient will be eligible for inclusion in the study if he/she fulfills the following criteria:
- 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.
Who cannot join
- A patient will not be eligible for inclusion in this study if they meet any of the following exclusion criteria:
- 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.
Trial locations and contacts
54 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
54 sites in 4 countries
Spain20 sites, 20 recruiting
- Recruiting
Instituto de Investigación Biomédica de A Coruña
A Coruña, 15006
Dr Maria del Mar Castellanos Rodrigo
- Recruiting
Complejo Hospitalario Universitario de Albacete
Albacete, Castille-La Mancha, 2006
Dr Tomas Segura Martin
- Recruiting
Hospital Universitario Infanta Cristina (HUB)
Badajoz, 06080
Dr Jose Maria Ramirez Moreno
- Recruiting
Hospital Germans Trias i Pujol
Badalona, Barcelona, 08916
María Hernández Pérez
- Recruiting
Hospital Universitario de Cruces
Barakaldo, 48903
Dr Mari Mar Freijo Guerrero
- Recruiting
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona, 08035
Carlos Alberto Molina Cateriano
- Recruiting
Hospital Clínico Universitario Virgen de Arrixaca
El Palmar, Murcia, 30120
Dr Ana Morales Ortiz
- Recruiting
Institut Catala d'Oncologia (ICO) - Hospital Universitari Doctor Josep Trueta
Girona, 17007
Dr Yolanda Silva Blas
- Recruiting
Hospital Universitario La Paz
Madrid, Madrid, 28046
Exuperio Díez Tejedor
- Recruiting
Hospital Universitario Puerta de Hierro Majadahonda
Madrid, Madrid, 28222
Dr Joaquin Carneado Ruiz
- Recruiting
Hospital Universitario Ramon y Cajal
Madrid, 28034
Dr Jaime Masjuan Vallejo
- Recruiting
Hospital Clinico San Carlos
Madrid, 28040
Dr Jose Antonio Egido Herrero
- Recruiting
Medical Imbrain S.L.
Melilla, 52001
Romero Imbroda, Jesus, jesusromeroimbroda@gmail.com
- Recruiting
Hospital Clinico Universitario de Santiago
Santiago, 15706
Dr Manuel Rodriguez Yanez
- Recruiting
Hospital Universitario Virgen Macarena
Seville, Sevilla, 41009
Soledad Pérez Sánchez
- Recruiting
Hospital Universitario Virgen del Rocio
Seville, 41013
Dr Francisco Moniche Alvarez
- Recruiting
Hospital Universitari Joan XXIII
Tarragona, Tarragona, 43005
Dr Xavier Ustrell Roig
- Recruiting
Hospital Clinico Universitario de Valencia
Valencia, 46010
Dr. Alejandro Ponz
- Recruiting
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, 46026
Dr Irene Escudero Martinez
- Recruiting
Hospital Universitario Miguel Servet
Zaragoza, 50009
Dr Herbert Tejada Meza
United States14 sites, 14 recruiting
- Recruiting
SSM Health Neurosciences
Bridgeton, Missouri, 63044
Amer Alshekhlee, MD
- Recruiting
Mercy Medical Group
Carmichael, California, 95608
Lucian Maidan, MD
- Recruiting
CHI Memorial Neuroscience Institute
Chattanooga, Tennessee, 37404
Thomas Devlin
- Recruiting
OSU Wexner Medical Center
Columbus, Ohio, 43210
Yousef Hannawi
- Recruiting
Guilford Neurologic Associates Inc
Greensboro, North Carolina, 27401
Dr. Pramod Sethi
- Recruiting
Penn State Health Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
Reichwein, Raymond, rreichwein@pennstatehealth.psu.edu
- Recruiting
Houston Medical Neurological Institute
Houston, Texas, 77030
David Chui, MD
- Recruiting
Memorial Hermann Hospital
Houston, Texas, 77030
Mahan Shahrivari, MD
- Recruiting
Wellstar Kennestone Hospital
Marietta, Georgia, 30060
Dr. Ovais Inamullah
- Recruiting
St. John's Regional Medical Center
Oxnard, California, 93030
Mani Nezhad
- Recruiting
Hackensack University Medical Center at Paramus
Paramus, New Jersey, 07652
Amory, Colum, colum.amory@hmhn.org
- Recruiting
UPMC Presbyterian Hospital
Pittsburgh, Pennsylvania, 15213
Dr Jussie Correia Lima
- Recruiting
Sarasota Memorial Hospital
Sarasota, Florida, 34239
Dr. Mauricio Concha
- Recruiting
The University of Arizona - College of Medicine
Tucson, Arizona, 85719
Kaddouh, Firas, firaskaddouh@arizona.edu
Germany11 sites, 11 recruiting
- Recruiting
Klinikum Altenburger Land GmbH
Altenburg, Altenburg, 04600
Joerg Berrouschot
- Recruiting
RHON-KLINIKUM Campus Bad Neustadt
Bad Neustadt an der Saale, 97616
Soda, Hassan, h.soda.akut@neurologie-bad-neustadt.de
- Recruiting
Charite-Universitaetsmedizin Berlin
Berlin, State of Berlin, 12203
Christian Nolte, christian.nolte@charite.de
- Recruiting
Universitaetsklinikum Erlangen
Erlangen, 91054
Gerner, Stefan, stefan.gerner@uk-erlangen.de
- Recruiting
Universitätsklinikum Essen AöR
Essen, 45147
Prof. Dr. med. Martin Köhrmann
- Recruiting
Universitaetsklinikum Goettingen
Göttingen, Lower Saxony, 37075
Ilko Maier
- Recruiting
Universitätsklinikum Schleswig-Holstein AöR
Lübeck, 23538
Prof. Dr. George Royl
- Recruiting
Muhlenkreiskliniken (MKK) - Johannes Wesling Klinikum Minden - Neurologische Klinik
Minden, North Rhine-Westphalia, 32427
Dr Peter Schellinger
- Recruiting
Klinik fuer Neurologie, Stroke Unit und Fruehrehabilitation Dorstener Strae 151
Recklinghausen, Recklinghausen, 45657
Dr Stephan Klebe
- Recruiting
Klinikum der Stadt Ludwigshafen gGmbh
Rhein, Ludwigshafen Am, 67063
Dr Simon Nagel
- Recruiting
University Hospital Tuebingen
Tübingen
Mengel, Anne Rose, sven.poli@uni-tuebingen.de
United Kingdom9 sites, 9 recruiting
- Recruiting
Fairfield General Hospital
Bury, Bury, BL9 7TD
Dr Narayanamoorthi Saravanan
- Recruiting
London North West University Healthcare NHS Trust - Northwick Park Hospital
Harrow, HA1 3UJ
Sivagnanaratnam, Aravinth, a.sivagnanaratnam@nhs.net
- Recruiting
National Hospital for Neurology & Neurosurgery
London, London, NW1 2BU
Dr Richard Perry
- Recruiting
King's College Hospital NHS Foundation Trust
London, London, SE5 9RS
Dr Yee Mah
- Recruiting
St. George's University Hospitals
London, London, SW17 0QT
Zhang, Liqun, liqun.zhang@stgeorges.nhs.uk
- Recruiting
Hospitals NHS Foundation Trust - Royal Victoria Infirmary RVI
Newcastle, NE1 4LP
Dr. Anand Dixit
- Recruiting
University Hospital Southampton
Southampton, Southampton, SO16 6YD
Dr Richard Marigold
- Recruiting
Royal Stoke University Hospital
Stoke-on-Trent, ST4 6QG
Ferdinand, Phillip, phillip.ferdinand@uhnm.nhs.uk
- Recruiting
New Cross Hospital - Royal Wolverhampton NHS Trust
Wolverhampton, Wolverhampton, WV10 0QP
Dr Nasar Ahmad
About this study
Official title: A Multicentric, Randomized, Double-blind, Parallel, Placebo-controlled Phase III Study to Assess the Safety and Efficacy of Sovateltide in Patients With Acute Cerebral Ischemic Stroke.
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.
Read the detailed description
A stroke is a syndrome defined as an abrupt neurological outburst due to impaired blood flow to part of the brain. There are two types of stroke: hemorrhagic stroke and ischemic stroke. A hemorrhagic stroke follows the rupture of a weakened blood vessel in the brain causing accumulation of blood and compression of the surrounding brain tissue. An ischemic stroke follows a blocked blood vessel by a thrombus (blood clot) or embolism. In both types of strokes, the specific region of the brain supplied by the affected blood vessel is deprived of oxygenated blood, causing local hypoxia that damages the brain tissue and cells. Both types of stroke are very serious, however ischemic stroke is more common.
The global burden of ischemic stroke is nearly 4-fold greater than hemorrhagic stroke with close to 87% of the total incidence of stroke attributed to acute cerebral ischemic stroke (ACIS). ACIS is a critical care emergency caused by a significant reduction in blood flow to the brain by a blood clot or embolism. This nearly halts cerebral blood flow to the affected region leading to neuronal death. Neuronal cell death is followed by plasma membrane disruption, swelling of organelles, leaking of cell contents into extracellular space, and loss of neuronal function. Other events that take place include inflammation, excitotoxicity, free radical mediated toxicity, cytokine mediated cytotoxicity, impaired blood-brain-barrier, and oxidative stress.
Therapeutic management of ACIS is a multidisciplinary approach with a primary goal of revascularization and limiting neuronal injury. A stroke team consists of emergency medicine physicians, neurologists/neurosurgeons, radiologists, nurses and advanced care providers, clinical pharmacists, therapists, technicians, and laboratory personnel. Currently, the only FDA-approved pharmacological agent for ischemic stroke is tissue plasminogen activator (t-PA). It is a thrombolytic agent which restores blood flow by breaking down a clot. However, timing is crucial in administration of t-PA as the therapeutic time window is very narrow and the patient must receive it within 4.5 hours of onset of stroke symptoms. Therapeutic administration after this timeframe can result in hemorrhagic transformation, leading to additional brain damage. Nevertheless, even upon timely administration of t-PA in ACIS, only about 30% of patients obtain stroke resolution having minimal or no disability at the 90-day mark.
Sovateltide (PMZ-1620, IRL-1620) is a highly selective ETB receptor agonist and a synthetic analog of ET-1. Studies conducted to determine the effects brought about by sovateltide upon its interaction with neural ETB receptors and have found that it enhances angiogenesis and neurogenesis as well as promotes neural repair and regeneration. In a rat model of ischemic stroke, sovateltide was found to be neuroprotective as well as enhance angiogenic and neurogenic remodeling. Sovateltide significantly improved survival, reduced neurological and motor function deficit, while effectively decreasing infarct volume, edema, and oxidative stress.
Sovateltide was also found to be safe and well tolerated in healthy human volunteers in a phase I clinical trial (CTRI/2016/11/007509). A phase II study was also conducted in patients with acute ischemic stroke where sovateltide demonstrated significant improvement when compared to standard of care (CTRI/2017/11/010654, NCT04046484). A recent phase III study conducted in patients of acute ischemic stroke demonstrated improved favorable functional and neurological outcome at 3 months compared to standard of care (CTRI/2019/09/021373, NCT04047563).
Clinical phase II and III results indicate that sovateltide is a first-in-class neuronal progenitor cell therapeutic that promotes quick recovery and significantly improves neurological outcomes in cerebral ischemic stroke patients. With this convincing evidence, the plan is to conduct a multicentric, randomized, double-blind, parallel, placebo-controlled phase III clinical study in the United States, Canada, United Kingdom and Europe (the demographics and standard of treatment being similar in these countries) to further assess the safety and efficacy of sovateltide in patients with acute cerebral ischemic stroke.
- Conditions
- Acute Ischemic Stroke, Cerebral Stroke
- Being tested
- Drug: Normal Saline, Sovateltide
- Keywords
- Endothelin B Receptors
- Medical subject headings
- Ischemic Stroke, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Drug: Normal SalineDrug
Also called Vehicle
Normal saline to be used as vehicle in the phase-III study to assess efficacy of sovateltide in patients with acute cerebral ischemic stroke.
SovateltideDrug
Also called PMZ-1620
Phase-III study to assess efficacy of sovateltide in patients with acute cerebral ischemic stroke.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Sovateltide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
The proportion of acute cerebral ischemic stroke patients having a good functional outcome with NIHSS score of <6 on day 90 post-randomization.
Measured: 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.
The proportion of acute cerebral ischemic stroke patients having a good functional outcome with BI score of ≥90 on day 90 post-randomization.
Measured: 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.
The proportion of acute cerebral ischemic stroke patients having an excellent functional outcome with a modified Rankin Scale score of 0-1 on day 90 post-randomization.
Measured: 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.
Change in QoL as assessed by EuroQol EQ-5D-5L and by SS-QOL from baseline to days 30, 60, and 90 post-randomization.
Measured: Day 1 through Day 90
Determine the incidence of recurrent cerebral ischemic stroke within 90 days post-randomization.
The proportion of patients with recurrent ischemic stroke within 90 days post-randomization.
Measured: Day 1 through Day 90
Determine the incidence of mortality within 90 days post-randomization.
Number of deaths within day 90 post-randomization.
Measured: Day 1 through Day 90
Determine the incidence of symptomatic Intracerebral Hemorrhage (ICH) within 24 (± 6) hours of randomization.
The proportion of patients with symptomatic ICH within 24 (± 6) hours of randomization.
Measured: Day 1 through Day 90
Determine the incidence of radiographic Intracerebral Hemorrhage (ICH) within 24 (± 6) hours of randomization.
The proportion of patients with radiographic ICH within 24 (± 6) hours of randomization.
Measured: Day 1 through Day 90
Determine alteration in cognition at days 30 and 90 measured by Montreal Cognitive Assessment (MoCA) Test.
Change in MoCA score at days 30 and 90 post-randomization.
Measured: Day 1 through Day 90
Determine any adverse events (AE) or serious adverse events (SAEs) are associated with sovateltide.
The proportion of patients with adverse events (AEs) and serious adverse events (SAEs).
Measured: Day 1 through Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2023
- Study start24 Jul 2025
- Primary completionSep 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Acute Ischemic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 514 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pharmazz, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Anil Gulati, MD, PhD, Study chair, Pharmazz, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05691244
- Sponsor's protocol ID
- Sovateltide/ACIS/IND2022
- Acronym
- RESPECT-ETB
- Status last verified
- Sep 2026
- First submitted
- 11 Jan 2023
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 39542995Ranjan 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.
PubMed 35328566Gulati 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.
PubMed 33428177Ramos 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.
PubMed 34826534Ranjan 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.
PubMed 32728189Ranjan 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.
PubMed 32574518Gulati 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.
PubMed 29947531Briyal 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.
PubMed 26022359Leonard 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.
PubMed 25806822Briyal 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.
PubMed 24561065Leonard 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.
PubMed 23850649Leonard 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.
PubMed 22580085Leonard 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.
PubMed 21959172Keam SJ. Sovateltide: First Approval. Drugs. 2023 Sep;83(13):1239-1244. doi: 10.1007/s40265-023-01922-4.
PubMed 37486545Briyal 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.
PubMed 36907516
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentric, Randomized, Double-blind, Parallel, Placebo-controlled Phase III Study to Assess the Safety and Efficacy of Sovateltide in Patients With Acute Cerebral Ischemic Stroke.
- ClinicalTrials.gov ID
- NCT05691244
- Acronym / sponsor ID
- RESPECT-ETB / Sovateltide/ACIS/IND2022
- Conditions
- Acute Ischemic Stroke, Cerebral Stroke
- Keywords
- Endothelin B Receptors
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 514 participants (estimated)
- Lead sponsor
- Pharmazz, Inc.Industry (pharma, biotech, devices)
- Study start
- 24 Jul 2025 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 19 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A stroke is a syndrome defined as an abrupt neurological outburst due to impaired blood flow to part of the brain. There are two types of stroke: hemorrhagic stroke and ischemic stroke. A hemorrhagic stroke follows the rupture of a weakened blood vessel in the brain causing accumulation of blood and compression of the surrounding brain tissue. An ischemic stroke follows a blocked blood vessel by a thrombus (blood clot) or embolism. In both types of strokes, the specific region of the brain supplied by the affected blood vessel is deprived of oxygenated blood, causing local hypoxia that damages the brain tissue and cells. Both types of stroke are very serious, however ischemic stroke is more common.
The global burden of ischemic stroke is nearly 4-fold greater than hemorrhagic stroke with close to 87% of the total incidence of stroke attributed to acute cerebral ischemic stroke (ACIS). ACIS is a critical care emergency caused by a significant reduction in blood flow to the brain by a blood clot or embolism. This nearly halts cerebral blood flow to the affected region leading to neuronal death. Neuronal cell death is followed by plasma membrane disruption, swelling of organelles, leaking of cell contents into extracellular space, and loss of neuronal function. Other events that take place include inflammation, excitotoxicity, free radical mediated toxicity, cytokine mediated cytotoxicity, impaired blood-brain-barrier, and oxidative stress.
Therapeutic management of ACIS is a multidisciplinary approach with a primary goal of revascularization and limiting neuronal injury. A stroke team consists of emergency medicine physicians, neurologists/neurosurgeons, radiologists, nurses and advanced care providers, clinical pharmacists, therapists, technicians, and laboratory personnel. Currently, the only FDA-approved pharmacological agent for ischemic stroke is tissue plasminogen activator (t-PA). It is a thrombolytic agent which restores blood flow by breaking down a clot. However, timing is crucial in administration of t-PA as the therapeutic time window is very narrow and the patient must receive it within 4.5 hours of onset of stroke symptoms. Therapeutic administration after this timeframe can result in hemorrhagic transformation, leading to additional brain damage. Nevertheless, even upon timely administration of t-PA in ACIS, only about 30% of patients obtain stroke resolution having minimal or no disability at the 90-day mark.
Sovateltide (PMZ-1620, IRL-1620) is a highly selective ETB receptor agonist and a synthetic analog of ET-1. Studies conducted to determine the effects brought about by sovateltide upon its interaction with neural ETB receptors and have found that it enhances angiogenesis and neurogenesis as well as promotes neural repair and regeneration. In a rat model of ischemic stroke, sovateltide was found to be neuroprotective as well as enhance angiogenic and neurogenic remodeling. Sovateltide significantly improved survival, reduced neurological and motor function deficit, while effectively decreasing infarct volume, edema, and oxidative stress.
Sovateltide was also found to be safe and well tolerated in healthy human volunteers in a phase I clinical trial (CTRI/2016/11/007509). A phase II study was also conducted in patients with acute ischemic stroke where sovateltide demonstrated significant improvement when compared to standard of care (CTRI/2017/11/010654, NCT04046484). A recent phase III study conducted in patients of acute ischemic stroke demonstrated improved favorable functional and neurological outcome at 3 months compared to standard of care (CTRI/2019/09/021373, NCT04047563).
Clinical phase II and III results indicate that sovateltide is a first-in-class neuronal progenitor cell therapeutic that promotes quick recovery and significantly improves neurological outcomes in cerebral ischemic stroke patients. With this convincing evidence, the plan is to conduct a multicentric, randomized, double-blind, parallel, placebo-controlled phase III clinical study in the United States, Canada, United Kingdom and Europe (the demographics and standard of treatment being similar in these countries) to further assess the safety and efficacy of sovateltide in patients with acute cerebral ischemic stroke.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Normal Saline + Standard of care | Active comparator | Drug: Drug: Normal SalineNormal 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. |
| Sovateltide + Standard of care | Experimental | Drug: SovateltideThe 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- A patient will be eligible for inclusion in the study if he/she fulfills the following criteria:
- 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.
Key exclusion criteria (8 listed)
- A patient will not be eligible for inclusion in this study if they meet any of the following exclusion criteria:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Drug: Normal SalineAlso: VehicleNormal saline to be used as vehicle in the phase-III study to assess efficacy of sovateltide in patients with acute cerebral ischemic stroke. | Drug | Normal Saline + Standard of care |
| SovateltideAlso: PMZ-1620Phase-III study to assess efficacy of sovateltide in patients with acute cerebral ischemic stroke. | Drug | Sovateltide + Standard of care |
Primary outcome
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.
Time frame: Day 1 through Day 90
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.
10 secondary outcomes
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Day 1 through Day 90
Determine the incidence of recurrent cerebral ischemic stroke within 90 days post-randomization.
Time frame: Day 1 through Day 90
Determine the incidence of mortality within 90 days post-randomization.
Time frame: Day 1 through Day 90
Determine the incidence of symptomatic Intracerebral Hemorrhage (ICH) within 24 (± 6) hours of randomization.
Time frame: Day 1 through Day 90
Determine the incidence of radiographic Intracerebral Hemorrhage (ICH) within 24 (± 6) hours of randomization.
Time frame: Day 1 through Day 90
Determine alteration in cognition at days 30 and 90 measured by Montreal Cognitive Assessment (MoCA) Test.
Time frame: Day 1 through Day 90
Determine any adverse events (AE) or serious adverse events (SAEs) are associated with sovateltide.
Time frame: Day 1 through Day 90
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Background: PubMed 39542995Gulati 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.
- Background: PubMed 35328566Ranjan 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.
- Background: PubMed 33428177Gulati 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.
- Background: PubMed 34826534Ramos 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.
- Background: PubMed 32728189Ranjan 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.
- Background: PubMed 32574518Ranjan 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.
- Background: PubMed 29947531Gulati 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.
- Background: PubMed 26022359Briyal 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.
- Background: PubMed 25806822Leonard 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.
- Background: PubMed 24561065Briyal 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.
- Background: PubMed 23850649Leonard 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.
- Background: PubMed 22580085Leonard 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Anil Gulati, MD, PhD study chair
Pharmazz, Inc.
54 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Drug: Normal Saline and Sovateltide in people with Acute Ischemic Stroke and Cerebral Stroke, run by Pharmazz, Inc. at 54 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 54 sites in Spain, United States, Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anil Gulati, MD, PhD (6307806087, anil.gulati@pharmazz.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: Day 1 through Day 90). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05691244, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.