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Cerebral IschemiaPhase 3NCT04047563

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

A Phase 3 study testing Normal Saline along with standard treatment and PMZ-1620 (sovateltide) along with standard treatment in people with Cerebral Ischemia and Cerebral Infarction, run by Pharmazz, Inc. at 11 sites in India.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

In the present prospective, multicentric, randomized, double-blind, parallel, saline-controlled phase II clinical study; the investigators plan to evaluate the efficacy of sovateltide (IRL-1620 or PMZ-1620) therapy along with standard supportive care in patients of acute ischemic stroke. Read more about this study

Who is it for?
Ages 18 to 78 years
What is being tested?
Normal Saline along with standard treatment and PMZ-1620 (sovateltide) along with standard treatment
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
158 participants
Where
11 sitesIndia
Study dates
10 Nov 2019to 10 Feb 2022
Phase
Phase 3
Are there results?
None posted in the registry

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 78 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult males or females Aged 18 years through 78 years (have not had their 79th birthday).
  • Patient or Legally Authorized Representative willing to give informed Consent before study procedure.
  • Stroke is ischemic in origin and radiologically confirmed Computed Tomography (CT) scan or diagnostic magnetic resonance imaging (MRI) prior to enrolment. No hemorrhage as proved by cerebral CT/MRI scan.
  • Cerebral ischemic stroke patients presenting upto 24 hours after onset of symptoms with mRS score of 3-4 (pre-stroke mRS score of 0 or 1) and NIHSS score >5 (NIHSS Level of Consciousness (1A) score must be < 2). This also includes patients who had ischemic stroke in the past and are completely recovered from earlier episode before having new or fresh stroke.
  • Patient is < 24 hours from time of stroke onset when the first dose of PMZ-1620 therapy is administered. Time of onset is when symptoms began; for stroke that occurred during sleep, time of onset is when patient was last seen or was self- reported to be normal.
  • Reasonable expectation of availability to receive the full PMZ-1620 course of therapy, and to be available for subsequent follow-up visits.

Who cannot join

  • Patients receiving endovascular therapy or is a candidate for any surgical intervention for treatment of stroke which may include but not limited to endovascular techniques.
  • Patients classified as comatose, defined as a patient who required repeated stimulation to attend, or is obtunded and requires strong or painful stimulation to make movements (NIHSS Level of Consciousness (1A) score ≥ 2).
  • Evidence of intracranial hemorrhage (intracerebral hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, epidural hemorrhage, acute or chronic subdural hematoma on the baseline CT or MRI scan.
  • Known pregnancy.
  • Confounding pre-existing neurological or psychiatric disease.
  • Concurrent participation in any other therapeutic clinical trial.
  • Evidence of any other major life-threatening or serious medical condition that would prevent completion of the study protocol, impair the assessment of outcome, or in which PMZ-1620 therapy would be contraindicated or might cause harm to the patient.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

India11 sites

  • Pushpanjali Hospital & Research Centre Pvt. Ltd

    Agra, Uttar Pradesh, 282002

  • Radiant Superspeciality Hospital

    Amravati, 444606

  • Post Graduate Institute of Medical Education and Research

    Chandigarh, 160012

  • Lalitha Superspecialities Hospital

    Guntur, 522001

  • Dayanand Medical College & Hospital

    Ludhiana, 141001

  • Department of Neurology, Christian Medical College and Hospital

    Ludhiana, 141008

  • Sidhu Hospital Pvt. Ltd.

    Ludhiana, 141421

  • New Era Hospital & Research Institute

    Nagpur, 440008

  • Chopda Medicare & Research Centre

    Nashik, 422005

  • All India Institute of Medical Sciences

    New Delhi, 110029

  • Indian Spinal Injury Centre

    New Delhi, 110070

Other trials in India

About this study

Official title: A Prospective, Multicentric, Randomized, Double-blind, Parallel, Phase III Clinical Study to Assess Efficacy of PMZ-1620 Along With Standard Treatment in Patients of Acute Ischemic Stroke

In the present prospective, multicentric, randomized, double-blind, parallel, saline-controlled phase II clinical study; the investigators plan to evaluate the efficacy of sovateltide (IRL-1620 or PMZ-1620) therapy along with standard supportive care in patients of acute ischemic stroke.

Read the detailed description

The peptide Sovateltide (IRL-1620) is a highly selective ETB receptor agonist. There are hidden stem cells in the brain, which becomes active following injury to the brain. Intravenous administration of PMZ-1620 (sovateltide) augments the activity of neuronal progenitor cells in the brain to repair the damage by formation of new mature neurons and blood vessels. In addition, PMZ-1620 has anti-apoptotic activity and also increases cerebral blood flow when administered following ischemia. It was discovered that in rat model of ischemic stroke, sovateltide, significantly improved survival, reduces neurological and motor function deficit while effectively decreasing infarct volume, edema and oxidative stress. The convincing results of preclinical efficacy studies of Sovateltide in ischemic stroke and its safety affirmation from phase I and phase II clinical studies encouraged us to investigate its efficacy in human patients of ischemic stroke. In the present prospective, multicentric, randomized, double-blind, parallel, saline-controlled phase II clinical study; the investigators plan to evaluate the efficacy of Sovateltide therapy along with standard supportive care in patients of acute ischemic stroke.

Being tested
Normal Saline along with standard treatment, PMZ-1620 (sovateltide) along with standard treatment
Keywords
Endothelin, Neurogenesis, Neural progenitor cells
Medical subject headings
Brain Ischemia, Cerebral Infarction, Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Normal Saline along with standard treatmentDrug

    Also called Vehicle

    PMZ-1620 (sovateltide) is an endothelin-B receptor agonist. PMZ-1620 has the potential to be a first-in-class neuronal progenitor cell therapeutics that is likely to promote quicker recovery and improve neurological outcome in cerebral ischemic stroke patients. In this arm normal saline along with standard treatment will be given for active comparison.

  • PMZ-1620 (sovateltide) along with standard treatmentDrug

    Also called PMZ-1620

    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.

Study groups in NCT04047563
Study groupRoleWhat they receive
Normal Saline + Standard of careActive comparatorPatients 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.
Receives: Drug: Normal Saline along with standard treatment
PMZ-1620 (sovateltide) + Standard of careExperimentalPatients 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).
Receives: Drug: PMZ-1620 (sovateltide) along with standard treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in National Institute of Health Stroke Scale (NIHSS)

    Neurological outcome as assessed by National Institute of Health Stroke Scale (NIHSS) score post randomization. NIHSS is 42 point scale where 0 is the best and 42 is the worst outcome.

    Measured: 90 days

  2. Change in modified Rankin Scale (mRS)

    Neurological outcome as assessed by modified Rankin Scale (mRS) score post randomization. mRS is a 7 grade scale from 0 to 6, where 0 is the best and 6 is the worst outcome.

    Measured: 90 days

  3. Change in Barthel index [BI]

    Overall clinical outcome as assessed by Barthel index [BI] scores) at 3 months post randomization. BI is a 10 item scale with scores ranging from 0 to 100, where a score of 100 is the best and 0 is the worst outcome.

    Measured: 90 days

  4. Change in the proportion of ischemic stroke patients with NIHSS score <6

    Change in the proportion of ischemic stroke patients with National Institute of Health Stroke Scale (NIHSS) score <6 at day 6, 1 month and 3 months. NIHSS is 42 point scale where 0 is the best and 42 is the worst outcome.

    Measured: 90 days

  5. Change in the proportion of ischemic stroke patients with mRS score <2

    Change in the proportion of ischemic stroke patients with modified Rankin Scale (mRS) score <2 at day 6, 1 month and 3 months. mRS is a 7 grade scale from 0 to 6, where 0 is the best and 6 is the worst outcome.

    Measured: 90 days

  6. Change in the proportion of ischemic stroke patients with Barthel index (BI) score >60

    Change in the proportion of ischemic stroke patients with Barthel index (BI) score >60 at day 6, 1 month and 3 months. BI is a 10 item scale with scores ranging from 0 to 100, where a score of 100 is the best and 0 is the worst outcome.

    Measured: 90 days

Secondary outcomes (6)

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

    Quality-of-life as assessed by EuroQol-EQ-5D will be determined at 1 month and 3 months post randomization. EuroQol-EQ-5D is a concise, generic instrument that could be used to measure, compare and value health status across disease areas. It is a five dimension instrument with scores ranging from 0 to 100, where a score of 100 is the best and 0 is the worst outcome.

    Measured: 90 days

  2. Change in Stroke-Specific Quality of Life (SSQOL)

    Stroke-Specific Quality of Life (SSQOL) will be assessed at 1 month and 3 months post randomization. SSQOL is composed of 49 items with scores ranging from 49 to 245, where a score of 245 is the best and 49 is the worst outcome.

    Measured: 90 days

  3. Incidence in recurrence of ischemic stroke

    Incidence of recurrent ischemic stroke within 1 month and 3 months post-randomization, as assessed by Questionnaire to Validate Stroke-Free Status

    Measured: 90 days

  4. Incidence of mortality

    Incidence of mortality within 3 months post-randomization

    Measured: 90 days

  5. Incidence of Intra-Cerebral Hemorrhage (ICH)

    Incidence of symptomatic Intra Cerebral Hemorrhage (ICH) within 24 (± 6) hours of randomization

    Measured: 30 hours

  6. Incidence of PMZ-1620 related adverse events

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

    Measured: 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Aug 2019
  2. Study start10 Nov 2019
  3. Primary completion10 Feb 2022
  4. Study completion10 Feb 2022

Resources

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
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
158 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04047563
Sponsor's protocol ID
PMZ-1620/CT-3.1/2019
Status last verified
Oct 2023
First submitted
5 Aug 2019
Last updated
18 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Results will be communicated and published as manuscript

Publications

  • 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.

    PubMed 31320660

  • 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.

    PubMed 30406063

  • 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.

    PubMed 29947531

  • 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.

    PubMed 26398673

  • 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.

    PubMed 23850649

  • 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.

    PubMed 22580085

  • 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.

    PubMed 21959172

  • 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.

    PubMed 32728189

  • 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.

    PubMed 32574518

  • 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.

    PubMed 33428177

  • 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 39542995

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Normal Saline along with standard treatment and PMZ-1620 (sovateltide) along with standard treatment in people with Cerebral Ischemia and Cerebral Infarction, run by Pharmazz, Inc. at 11 sites in India.

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 6 inclusion and 7 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: finished, as of the sponsor's last update on 18 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in India. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in National Institute of Health Stroke Scale (NIHSS) (time frame: 90 days). The study lists 6 primary outcomes in all. 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 NCT04047563, which also lists 11 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 18 Oct 2023.

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