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

Sponsor

Pharmazz, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT04047563

Collaborator

(none)

158

Enrollment

Locations

Arms

Actual Duration (Months)

14.4

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

158 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.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

Actual Study Start Date :

Nov 10, 2019

Actual Primary Completion Date :

Feb 10, 2022

Actual Study Completion Date :

Feb 10, 2022

Arms and Interventions

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 Names: 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 Names: PMZ-1620

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 Names:

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

Other Names:

PMZ-1620

Outcome Measures

Primary Outcome Measures

Change in National Institute of Health Stroke Scale (NIHSS) [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.
Change in modified Rankin Scale (mRS) [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.
Change in Barthel index [BI] [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.
Change in the proportion of ischemic stroke patients with NIHSS score <6 [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.
Change in the proportion of ischemic stroke patients with mRS score <2 [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.
Change in the proportion of ischemic stroke patients with Barthel index (BI) score >60 [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

Change in Quality-of-life as assessed by EuroQol-EQ-5D [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.
Change in Stroke-Specific Quality of Life (SSQOL) [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.
Incidence in recurrence of ischemic stroke [90 days]
Incidence of recurrent ischemic stroke within 1 month and 3 months post-randomization, as assessed by Questionnaire to Validate Stroke-Free Status
Incidence of mortality [90 days]
Incidence of mortality within 3 months post-randomization
Incidence of Intra-Cerebral Hemorrhage (ICH) [30 hours]
Incidence of symptomatic Intra Cerebral Hemorrhage (ICH) within 24 (± 6) hours of randomization
Alteration in cognition [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.
Incidence of PMZ-1620 related adverse events [90 days]
Another objective of the study is to determine incidence of drug (PMZ-1620) related adverse events.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 78 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pushpanjali Hospital & Research Centre Pvt. Ltd	Agra	Uttar Pradesh	India	282002
2	Radiant Superspeciality Hospital	Amravati		India	444606
3	Post Graduate Institute of Medical Education and Research	Chandigarh		India	160012
4	Lalitha Superspecialities Hospital	Guntur		India	522001
5	Dayanand Medical College & Hospital	Ludhiana		India	141001
6	Department of Neurology, Christian Medical College and Hospital	Ludhiana		India	141008
7	Sidhu Hospital Pvt. Ltd.	Ludhiana		India	141421
8	New Era Hospital & Research Institute	Nagpur		India	440008
9	Chopda Medicare & Research Centre	Nashik		India	422005
10	All India Institute of Medical Sciences	New Delhi		India	110029
11	Indian Spinal Injury Centre	New Delhi		India	110070