CTRI/2017/11/010654 [Registered on: 27/11/2017] Trial Registered Prospectively
Last Modified On:
10/02/2023
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group Trial
Public Title of Study
To Study the effect of PMZ-1620 in stroke patients.
Scientific Title of Study
A Prospective, Multicentric, Randomized, Double Blind, Parallel, Saline Controlled
Phase II Clinical Study to Compare the Safety and Efficacy of PMZ-1620 Therapy along
with Standard Supportive Care in Subjects of Acute Ischemic Stroke.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
PMZ-01, Version 2.0, Dated 18 April 2016
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Jeyaraj Durai Pandian
Designation
Principal Investigator
Affiliation
Christian Medical College and Hospital
Address
Department of Neurology, Christian Medical College and Hospital, Brown Road
Ludhiana PUNJAB 141008 India
Phone
9915784750
Fax
01612220850
Email
jeyarajpandian@hotmail.com
Details of Contact Person Scientific Query
Name
Dr Manish S Lavhale
Designation
Associate Director
Affiliation
Pharmazz India Private Limited
Address
Department of Research and Development
H-6, Site-C, Surajpur Industrial Area, Greater Noida
Gautam Buddha Nagar UTTAR PRADESH 201307 India
Phone
9873847397
Fax
Email
manish.lavhale@pharmazz.com
Details of Contact Person Public Query
Name
Mr Sunil Gulati
Designation
Chief Operating Officer
Affiliation
Pharmazz India Private Limited
Address
Department of Research and Development
H-6, Site-C, Surajpur Industrial Area, Greater Noida
Gautam Buddha Nagar UTTAR PRADESH 201307 India
Phone
9811406340
Fax
Email
sunil.gulati@pharmazz.com
Source of Monetary or Material Support
Pharmazz India Private Limited, H-6,
Site-C,
Surajpur Industrial Area, Greater
Noida UP 201307
Drug Trial Ethics Committee, Ethics Committee Office, Room No. 6, Administrative Block, Basement, Hero DMC Heart Institute, Dayanand Medical College and Hospital, Tagore Nagar, Civil Lines, Ludhiana 141001, Punjab
Approved
Ethics Committee, All India Institute of Medical Sciences, Room No. 102, 1st Floor, Old OT Block AIIMS, Ansari Nagar, New Delhi-110029, India
Approved
Ethics Committee, New Era Hospital, Central Avenue Road, Near Telephone Exchange Chowk, Queta Colony, Near Jalaram Mandir, Nagpur-440008, Maharashtra, India
Approved
Institutional Ethics Committee Christian Medical College & Hospital Christian Medical College & Hospital, Brown Road, Ludhiana, Punjab-141008, India.
Approved
Institutional Ethics Committee, Paras Hospital, C-1, Sushant Lok Phase 1, Sector-43, Gurgaon-122002, Haryana, India
Approved
Institutional Ethics Committee, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI) Bioethics Cell, Room No. 205, 1st Floor, Administrative Block, Raebareli Road, Lucknow -226014 Uttar Pradesh, India
Approved
NIMS Institutional Ethics Committee Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad-500082
Acute Ischemic Stroke, (1) ICD-10 Condition: I635||Cerebral infarction due to unspecified occlusion or stenosis of cerebral arteries,
Intervention / Comparator Agent
Type
Name
Details
Intervention
IRL-1620 For Injection (PMZ-1620)
PMZ-1620 + Standard of care: Three 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). PMZ-1620 will be administered as an intravenous bolus dose over 1 minute within 24 hours of the stroke onset.
Comparator Agent
Normal Saline
Normal Saline (Dose: Equal volume) + Standard of care: Three 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. Normal Saline will be administered as an intravenous bolus dose over 1 minute within 24 hours of the stroke onset.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
70.00 Year(s)
Gender
Both
Details
1. Adult males or females Aged 18 years through 70 years (have not had their 71st birthday)
2. Signed and dated informed Consent from Legally Acceptable Representative, if subject is not in the condition to give consent. However, when the subject is stable and is able to give consent, consent would be obtained on a separate informed consent form to confirm his/her willingness to continue in the study.
3.Stroke is ischemic in origin, supratentorial, and radiologically confirmed Computed Tomography (CT) scan or diagnostic magnetic resonance imaging (MRI) prior to enrolment.
4. New (first time) cerebral ischemic strokes subjects presenting up to 24 hours after onset of symptoms (mRS score of 3-4) with
a prestroke mRS score of 0 or 1 and NIHSS score of 5-14).
5. No hemorrhage as proved by cerebral CT/MRI scan.
6. Subject 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 subject was last seen or was self reported to be normal.
7.Reasonable expectation of availability to receive the full PMZ-1620 course of therapy, and to be available for subsequent follow-up visits.
8. Subjects receiving thrombolytic therapy.
9. Reasonable expectation that subject will receive standard post stroke physical, occupational, speech, and cognitive therapy as
indicated.
10. Female subject is either:
a. Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) or,
b. If of childbearing potential, agrees to use any of the following effective separate forms of contraception throughout the study, up to and including the follow-up visits: Condoms, sponge, foams, jellies, diaphragm or intrauterine device, OR A vasectomised partner OR abstinence.
ExclusionCriteria
Details
1. Subjects receiving endovascular therapy
2. Subjects presenting with lacunar, hemorrhagic and/or brain stem stroke.
3. Subjects classified as comatose, defined as a subject who required repeated stimulation to attend, or is obtunded and requires strong or painful stimulation to make movements (NIHSS Level of Consciousness (1A) score must be < 2).
4. Episode/exacerbation of congestive heart failure (CHF) from any cause in the last 6 months. (An episode of CHF is any heart
failure that required a change in medication, change in diet or hospitalization).
5. 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.
6. Known valvular heart disease with CHF in the last 6 months.
7. Known (or in the Investigator’s clinical judgment) existence of severe aortic stenosis or mitral stenosis.
8. Cardiac surgery involving thoracotomy (e.g., coronary artery bypass graft, (CABG), valve replacement surgery) in the last 6 months.
9. Subject is a candidate for any surgical intervention for treatment of stroke which may include but not limited to endovascular techniques.
10. Subjects who are obese, body mass index (BMI) > 30 and/or on hormonal contraceptives.
11. Hypo- or hyperglycemia sufficient to account for the neurological symptoms; patient should be excluded if their blood glucose is < 3.0 or > 20.0 mmol/L.
12. Patient has systolic BP < 90 mmHg or > 220 mmHg or diastolic BP < 40 mmHg or > 130 mmHg.
13. Acute myocardial infarction in the last 6 months.
14. Signs or symptoms of acute myocardial infarction, including electrocardiogram findings, on admission.
15. Concomitant treatment with neuroprotective or nootropic drugs (e.g. piracetam, citicoline, investigational, neuroprotective substances).
16. Qualitative estimation of troponin on admission.
17. Suspicion of aortic dissection on admission.
18. Acute arrhythmia (including any tachy- or bradycardia) with hemodynamic instability on admission (systolic BP < 100 mmHg).
19. Findings on physical examination of any of the following:
(1) jugular venous distention (JVP > 4 cm above the sternal angle);
(2) 3rd heart sound;
(3) resting tachycardia (heart rate > 100/min) attributable to CHF;
(4) lower extremity pitting edema attributable to CHF;
(5) bilateral rales; and/or
(6) if a chest x-ray is performed, definite evidence of pulmonary edema, bilateral pleural effusion, or pulmonary vascular redistribution.
20. Current acute or chronic lung disease requiring supplemental chronic or intermittent oxygen therapy.
21. Serum creatinine > 2.0 mg/dL or 180 μmol/L.
22. Severe chronic anemia (hemoglobin < 7.5 g/dL).
23. Pregnancy, breastfeeding or positive pregnancy test. (Women of childbearing age must have a negative pregnancy test prior to study drug administration).
24. Concurrent participation in any other therapeutic clinical trial.
25. 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 subject.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Proportion of subjects with adverse events (AEs) and serious adverse events (SAEs)
3 Months
Secondary Outcome
Outcome
TimePoints
Change in proportion of subjects with NIHSS score ≥ 6.
From baseline to 3 months post randomization.
Change in proportion of subjects with drop in mRS score ≤ 2 or a score of 0.
From baseline to day 6, day 12, 1 month, and 3 month post randomization.
Proportion of subjects with overall clinical outcome as assessed by the global
statistical test of NIHSS, mRS, and BI scores.
At 3 months post randomization.
Change in proportion of subjects with mRS score ≤ 2.
From baseline to day 6 and 1 month post randomization.
Change in proportion of subjects with mRS score ≤ 2 and BI ≥ 60.
From baseline to day 6, 1 month, and 3 months post randomization
Change in QoL score.
From baseline to 2 and 3 months post randomization.
Proportion of subjects with recurrent ischemic stroke.
Within 1 month and 3 months.
Number of deaths.
Within 3 months post-randomization.
Proportion of subjects with symptomatic ICH.
within 24 (± 6) hours of randomization.
Average amount of time taken to complete the task in TMTs A and B.
At 3 months post-randomization.
Target Sample Size
Total Sample Size="40" Sample Size from India="40" Final Enrollment numbers achieved (Total)= "40" Final Enrollment numbers achieved (India)="40"
1. 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.
2. 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.
3. 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.
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
This is a prospective, multicentric, randomized, double blind, parallel, saline controlled Phase II clinical study to compare the safety and efficacy of PMZ-1620 therapy along with standard supportive care in subjects of acute ischemic stroke. Total 40 subjects will be enrolled in the study. The enrolment period of the study will be approximately 12 months and total duration of the study will be approximately 15 months. For an individual subject, duration of the study will be 3 months (90 days), including 5 study visits: visit 1/Day 1 (screening/baseline/treatment visit), visit 2/Day 12, visit 3 (Day 30 ± 5), visit 4/telephonic visit (Day 60 ± 5), and visit 5/End of Study (Day 90 ± 5). At visit 1, approximately 40 subjects will be randomized 1:1 into 2 treatment groups after meeting the eligibility criteria:
Group 1: PMZ-1620 + Standard of care
Group 2: Normal Saline (Dose: Equal volume) + Standard of care
PMZ-1620 or saline will be administered as an intravenous (IV) bolus dose over 1 minute within the window of 24 hours after the onset of stroke. In PMZ group, 3 doses of PMZ-1620, at 0.3 μg/kg body weight will be administered as an (IV) 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 saline group, 3 doses of equal volume of normal saline will be administered as a IV bolus over 1 minute every 3 hours ± 1 hour on day 1, 3 and day 6 post randomization. In both treatment groups, subjects will be provided the standard of care. Standard of care to be provided to the patients shall be the one used in the particular hospital setup. Each subject will be monitored closely throughout his/her hospitalization for the qualifying stroke and will be followed for 3 months from randomization. Each subject will be assessed for efficacy and safety parameters over 3 months from randomization at a clinic visit. Each subject will be contacted by telephone for brief (< 30 minutes) clinical and QoL assessments at 2 months ± 5 days (visit 4) from randomization.