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

NCT ID: NCT05691244

Last Updated: 2025-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

514 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-24

Study Completion Date

2026-11-30

Brief Summary

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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

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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

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Acute Ischemic Stroke Cerebral Stroke

Keywords

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Endothelin B Receptors

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
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.

Study Groups

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Normal Saline + Standard of care

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.

Group Type ACTIVE_COMPARATOR

Drug: Normal Saline

Intervention Type 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.

Sovateltide + Standard of care

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.

Group Type EXPERIMENTAL

Sovateltide

Intervention Type DRUG

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

Interventions

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Drug: Normal Saline

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

Intervention Type DRUG

Sovateltide

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

Intervention Type DRUG

Other Intervention Names

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Vehicle PMZ-1620

Eligibility Criteria

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Inclusion Criteria

A patient will be eligible for inclusion in the study if he/she fulfills the following criteria:

1. Adult males or females aged 18 - 80 years of age.
2. Consent obtained per national laws and regulations, and in accordance with the applicable ethics committee requirements prior to study procedures.
3. 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.
4. 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.
5. 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.
6. Reasonable expectation of availability to receive the full sovateltide/placebo course of therapy and to be available for subsequent follow-up visits.

Exclusion Criteria

1. 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.
2. 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).
3. 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.
4. Known pregnancy and lactating women.
5. 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.
6. Concurrent participation in any other therapeutic clinical trial.
7. 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pharmazz, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Anil Gulati, MD, PhD

Role: STUDY_CHAIR

Pharmazz, Inc.

Locations

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The University of Arizona - College of Medicine

Tuscon, Arizona, United States

Site Status RECRUITING

Mercy Medical Group

Carmichael, California, United States

Site Status RECRUITING

St. John's Regional Medical Center

Oxnard, California, United States

Site Status RECRUITING

SSM Health Neurosciences

Bridgeton, Missouri, United States

Site Status RECRUITING

OSU Wexner Medical Center

Columbus, Ohio, United States

Site Status RECRUITING

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

CHI Memorial Neuroscience Institute

Chattanooga, Tennessee, United States

Site Status RECRUITING

Houston Medical Neurological Institute

Houston, Texas, United States

Site Status RECRUITING

Memorial Hermann Hospital

Houston, Texas, United States

Site Status RECRUITING

Klinikum Altenburger Land GmbH

Altenburg, Altenburg, Germany

Site Status RECRUITING

Universitaetsklinikum Goettingen

Göttingen, Lower Saxony, Germany

Site Status RECRUITING

Klinikum der Stadt Ludwigshafen gGmbh

Rhein, Ludwigshafen Am, Germany

Site Status RECRUITING

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

Minden, North Rhine-Westphalia, Germany

Site Status RECRUITING

Klinik fuer Neurologie, Stroke Unit und Fruehrehabilitation Dorstener Strae 151

Recklinghausen, Recklinghausen, Germany

Site Status RECRUITING

Charite-Universitaetsmedizin Berlin

Berlin, State of Berlin, Germany

Site Status RECRUITING

Universitätsklinikum Essen AöR

Essen, , Germany

Site Status RECRUITING

Universitätsklinikum Schleswig-Holstein AöR

Lübeck, , Germany

Site Status RECRUITING

Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Site Status RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona, Spain

Site Status RECRUITING

Complejo Hospitalario Universitario de Albacete

Albacete, Castille-La Mancha, Spain

Site Status RECRUITING

Hospital Universitario La Paz

Madrid, Madrid, Spain

Site Status RECRUITING

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, Madrid, Spain

Site Status RECRUITING

Hospital Clínico Universitario Virgen de Arrixaca

El Palmar, Murcia, Spain

Site Status RECRUITING

Hospital Universitario Virgen Macarena

Seville, Sevilla, Spain

Site Status RECRUITING

Hospital Universitari Joan XXIII

Tarragona, Tarragona, Spain

Site Status RECRUITING

Instituto de Investigación Biomédica de A Coruña

A Coruña, , Spain

Site Status RECRUITING

Hospital Universitario Infanta Cristina (HUB)

Badajoz, , Spain

Site Status RECRUITING

Hospital Universitario de Cruces

Barakaldo, , Spain

Site Status RECRUITING

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

Girona, , Spain

Site Status RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status RECRUITING

Hospital Clinico San Carlos

Madrid, , Spain

Site Status RECRUITING

Hospital Clinico Universitario de Santiago

Santiago, , Spain

Site Status RECRUITING

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status RECRUITING

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

Site Status RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Site Status RECRUITING

Fairfield General Hospital

Bury, Bury, United Kingdom

Site Status RECRUITING

National Hospital for Neurology & Neurosurgery

London, London, United Kingdom

Site Status RECRUITING

King's College Hospital NHS Foundation Trust

London, London, United Kingdom

Site Status RECRUITING

University Hospital Southampton

Southampton, Southampton, United Kingdom

Site Status RECRUITING

New Cross Hospital - Royal Wolverhampton NHS Trust

Wolverhampton, Wolverhampton, United Kingdom

Site Status RECRUITING

Hospitals NHS Foundation Trust - Royal Victoria Infirmary RVI

Newcastle, , United Kingdom

Site Status RECRUITING

Countries

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United States Germany Spain United Kingdom

Central Contacts

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Anil Gulati, MD, PhD

Role: CONTACT

Phone: 6307806087

Email: [email protected]

Neil Marwah, MD

Role: CONTACT

Phone: 6307806087

Email: [email protected]

Facility Contacts

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Firas Kaddouh, MD

Role: primary

Lucian Maidan, MD

Role: primary

Mani Nezhad

Role: primary

Amer Alshekhlee, MD

Role: primary

Yousef Hannawi

Role: primary

Dr Jussie Correia Lima

Role: primary

Thomas Devlin

Role: primary

David Chui, MD

Role: primary

Mahan Shahrivari, MD

Role: primary

Joerg Berrouschot

Role: primary

Ilko Maier

Role: primary

Dr Simon Nagel

Role: primary

Dr Peter Schellinger

Role: primary

Dr Stephan Klebe

Role: primary

Christian Nolte

Role: primary

Prof. Dr. med. Martin Köhrmann

Role: primary

Prof. Dr. George Royl

Role: primary

María Hernández Pérez

Role: primary

Carlos Alberto Molina Cateriano

Role: primary

Dr Tomas Segura Martin

Role: primary

Exuperio Díez Tejedor

Role: primary

Dr Joaquin Carneado Ruiz

Role: primary

Dr Ana Morales Ortiz

Role: primary

Soledad Pérez Sánchez

Role: primary

Dr Xavier Ustrell Roig

Role: primary

Dr Maria del Mar Castellanos Rodrigo

Role: primary

Dr Jose Maria Ramirez Moreno

Role: primary

Dr Mari Mar Freijo Guerrero

Role: primary

Dr Yolanda Silva Blas

Role: primary

Dr Jaime Masjuan Vallejo

Role: primary

Dr Jose Antonio Egido Herrero

Role: primary

Dr Manuel Rodriguez Yanez

Role: primary

Dr Francisco Moniche Alvarez

Role: primary

Dr. Alejandro Ponz

Role: primary

Dr Irene Escudero Martinez

Role: primary

Dr Herbert Tejada Meza

Role: primary

Dr Narayanamoorthi Saravanan

Role: primary

Dr Richard Perry

Role: primary

Dr Yee Mah

Role: primary

Dr Richard Marigold

Role: primary

Dr Nasar Ahmad

Role: primary

Dr. Anand Dixit

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 39542995 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35328566 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33428177 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34826534 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32728189 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32574518 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29947531 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26022359 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25806822 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24561065 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23850649 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22580085 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21959172 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 37486545 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36907516 (View on PubMed)

Other Identifiers

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Sovateltide/ACIS/IND2022

Identifier Type: -

Identifier Source: org_study_id