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

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ClinicalTrials.gov Identifier: NCT04047563
Recruitment Status : Recruiting
First Posted : August 6, 2019
Last Update Posted : October 4, 2019
Sponsor:
Information provided by (Responsible Party):
Pharmazz, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Cerebral Ischemia Cerebral Infarction Stroke, Acute Drug: Normal Saline along with standard treatment Drug: PMZ-1620 (sovateltide) along with standard treatment Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : August 2020

Arm Intervention/treatment
Active Comparator: Normal Saline + Standard of care
Patients will receive the best available standard of care. In control group, 3 doses of equal volume of normal saline will be administered as an IV bolus over 1 minutes every 3 hours ± 1 hour on day 1, 3 and day 6 post randomization.
Drug: Normal Saline along with standard treatment
PMZ-1620 (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.
Other Name: Vehicle

Experimental: PMZ-1620 (sovateltide) + Standard of care
Patients will receive the best available standard of care. In PMZ group, 3 doses of PMZ-1620, at 0.3 μg/kg body weight will be administered as an intravenous bolus over 1 minute every 3 hours ± 1 hour on day 1, 3, and day 6 (total dose/day: 0.9 µg/kg body weight).
Drug: PMZ-1620 (sovateltide) along with standard treatment
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.
Other Name: PMZ-1620




Primary Outcome Measures :
  1. Change in National Institute of Health Stroke Scale (NIHSS) [ Time Frame: 90 days ]
    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.

  2. Change in modified Rankin Scale (mRS) [ Time Frame: 90 days ]
    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.

  3. Change in Barthel index [BI] [ Time Frame: 90 days ]
    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.

  4. Change in the proportion of ischemic stroke patients with NIHSS score <6 [ Time Frame: 90 days ]
    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.

  5. Change in the proportion of ischemic stroke patients with mRS score <2 [ Time Frame: 90 days ]
    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.

  6. Change in the proportion of ischemic stroke patients with Barthel index (BI) score >60 [ Time Frame: 90 days ]
    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.


Secondary Outcome Measures :
  1. Change in Quality-of-life as assessed by EuroQol-EQ-5D [ Time Frame: 90 days ]
    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.

  2. Change in Stroke-Specific Quality of Life (SSQOL) [ Time Frame: 90 days ]
    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.

  3. Incidence in recurrence of ischemic stroke [ Time Frame: 90 days ]
    Incidence of recurrent ischemic stroke within 1 month and 3 months post-randomization, as assessed by Questionnaire to Validate Stroke-Free Status

  4. Incidence of mortality [ Time Frame: 90 days ]
    Incidence of mortality within 3 months post-randomization

  5. Incidence of Intra-Cerebral Hemorrhage (ICH) [ Time Frame: 30 hours ]
    Incidence of symptomatic Intra Cerebral Hemorrhage (ICH) within 24 (± 6) hours of randomization

  6. Alteration in cognition [ Time Frame: 90 days ]
    Cognition will be measured at 1 month and 3 months by Montreal Cognitive Assessment (MoCA) Test. Scores on the MoCA range from zero to 30, with a score of 26 and higher generally considered normal.

  7. Incidence of PMZ-1620 related adverse events [ Time Frame: 90 days ]
    Another objective of the study is to determine incidence of drug (PMZ-1620) related adverse events.



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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 78 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult males or females Aged 18 years through 78 years (have not had their 79th birthday).
  2. Patient or Legally Authorized Representative willing to give informed Consent before study procedure.
  3. 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.
  4. 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.
  5. 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.
  6. Reasonable expectation of availability to receive the full PMZ-1620 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 treatment of stroke which may include but not limited to endovascular techniques.
  2. 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).
  3. Evidence of intracranial hemorrhage (intracerebral hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, epidural hemorrhage, acute or chronic subdural hematoma on the baseline CT or MRI scan.
  4. Known pregnancy.
  5. Confounding pre-existing neurological or psychiatric disease.
  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 PMZ-1620 therapy would be contraindicated or might cause harm to the patient.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04047563


Contacts
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Contact: Manish S Lavhale +91 9873847397 manish.lavhale@pharmazz.com
Contact: Ravi Kant +91 8130786072 ravi.kant@pharmazz.com

Locations
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India
Radiant Superspeciality Hospital Recruiting
Amravati, India, 444606
Contact: Sikandar Adwani       sikandaradwani@yahoo.co.in   
Post Graduate Institute of Medical Education and Research Not yet recruiting
Chandigarh, India, 160012
Contact: Dheeraj Khurana Dheeraj Khurana       dherajk@yahoo.com   
Lalitha Superspecialities Hospital Not yet recruiting
Guntur, India, 522001
Contact: P. Vijaya       vijayapvr@yahoo.com   
Dayanand Medical College & Hospital Not yet recruiting
Ludhiana, India, 141001
Contact: Birinder S Paul       drbirinder06@yahoo.co.in   
Department of Neurology, Christian Medical College and Hospital Not yet recruiting
Ludhiana, India, 141008
Contact: Jeyaraj D Pandian       jeyarajpandian@hotmail.com   
Sidhu Hospital Pvt. Ltd. Not yet recruiting
Ludhiana, India, 141421
Contact: Gursaran K Sidhu       gursaransidhu@gmail.com   
New Era Hospital & Research Institute Not yet recruiting
Nagpur, India, 440008
Contact: Nilesh R Agrawal       anileshr@gmail.com   
Chopda Medicare & Research Centre Not yet recruiting
Nashik, India, 422005
Contact: Amit Yeole       amit_yeole37@rediffmail.com   
All India Institute of Medical Sciences Not yet recruiting
New Delhi, India, 110029
Contact: Deepti Vibha       deeptivibha@gmail.com   
Indian Spinal Injury Centre Not yet recruiting
New Delhi, India, 110070
Contact: A.K. Sahani       neurologist@isiconline.org   
Sponsors and Collaborators
Pharmazz, Inc.
Investigators
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Study Chair: Anil Gulati, MD, PhD Chairman and CEO

Publications:

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Responsible Party: Pharmazz, Inc.
ClinicalTrials.gov Identifier: NCT04047563     History of Changes
Other Study ID Numbers: PMZ-1620/CT-3.1/2019
First Posted: August 6, 2019    Key Record Dates
Last Update Posted: October 4, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Results will be communicated and published as manuscript

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pharmazz, Inc.:
Endothelin
Neurogenesis
Neural progenitor cells
Additional relevant MeSH terms:
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Stroke
Pathologic Processes
Cerebral Infarction
Brain Ischemia
Infarction
Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Necrosis
Brain Infarction