CTRI/2019/09/021373 [Registered on: 23/09/2019] Trial Registered Prospectively
Last Modified On:
27/08/2022
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group Trial
Public Title of Study
PMZ-1620 for the treatment of stroke.
Scientific Title of Study
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.
Department of
Neurology,
Neurosciences
Centre, Room No.:
707, 7th Floor,
Ansari Nagar, New
Delhi-110029 New Delhi DELHI
9968859848 01126593491 deeptivibha@gmail.com
Dr Ummer Karadan
Baby Memorial Hospital
Kozhikode, Kerala State Indira Gandhi Road Puthiyara Post Kozhikode Kozhikode Kerala - 673004 India Kozhikode KERALA
9447843954
ummerneuro@yahoo.co.in
Dr Alak Pandit
Bangur Institute of Neurosciences, IPGME&R/SSKM Hospital
Department of Neurology
Bangur Institute of Neurosciences, IPGME&R/SSKM Hospital
8, Sambhunath Pandit Street Bhowanipore
West Bengal, Kolkata-700020, India.
Kolkata WEST BENGAL
9831237725
dralakpandit@gmail.com
Dr Mohit Goel
Batra Hospital and Medical Research Centre
Department of Neurology, Batra Neuro Sciences Centre, Batra Hospital and Medical Research Centre,l Tughlakabad Institutional Area Mehrauli Badarpur Road, New Delhi-110062 South West DELHI
Department of
Neurology,Room No. - 195, Ground Floor, Christian Medical College and Hospital, Brown Road, Ludhiana -141008 Ludhiana PUNJAB
9915784750 01612220850 jeyarajpandian@hotmail.com
Dr Birinder Singh Paul
Dayanand Medical College & Hospital
Department of Neurology,Third Floor,
Dayanand Medical College & Hospital,
Civil Lines, Tagore Nagar, Ludhiana-141001, Punjab Ludhiana PUNJAB
9878045330
drbirinder06@yahoo.co.in
Dr Sanjay Ramteke
Government Medical College - Nagpur
Hanuman Nagar, Medical Square, Ajni
Nagpur-440008, Maharashtra Nagpur MAHARASHTRA
9890332286
ssrt95@yahoo.co.in
Dr Vijay Sardana
Government Medical College and Attached Hospitals, Kota
Government Medical College and Attached Hospitals,Rangbari Road, Sector - A, Rangbari, Kota, Rajasthan - 324002 Kota RAJASTHAN
9829086690
vsard13@gmail.com
Dr NV Sundarachary
Guntur Medical College & Government General Hospital
Department of Neurology
Guntur Medical College & Government General Hospital, Podila Prasad Super Specialty Block III rd Floor,
Guntur - 522 001
Andhra Pradesh, India. Guntur ANDHRA PRADESH
Institute of Medical Sciences, Banaras Hindu University
Department of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi - Uttar Pradesh, 221005 Varanasi UTTAR PRADESH
9918978666
drdeepikajoshi73@gmail.com
Dr Sidharth Shankar Anand
Institute of Neurosciences Kolkata
185/1 AJC Bose Road, West Bangal,
9th Floor Research Room,
Kolkata- 700017 Kolkata WEST BENGAL
9641469587
drsidharthsa@gmail.com
Dr Harsha S
JSS Hospital
Department of Super Specialty – Neurology , JSS Hospital, MG Road, Mysuru-570004, Karnataka Mysore KARNATAKA
9343524478
drharshaneur@gmail.com
Dr TCR Ramakrishnan
KG Hospital and Post Graduate Medical Institute
Door No 5 Arts College Road Coimbatore 641018 Tamil Nadu Coimbatore TAMIL NADU
9443365792
kgneuro@gmail.com
Dr Sulekha Saxena
King Georges Medical University
Department of Critical Care Medicine, King George’s Medical University, Trauma Center, Shah Mina Rd, Chowk, Lucknow, Uttar Pradesh 226003 Lucknow UTTAR PRADESH
Drug Trial Ethics Committee (DTEC), Dayanand Medical College & Hospital, 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, Guntur Medical College & Government General Hospital, Kannavari Thota, Kothapeta, Guntur-522004, Andhra Pradesh, India
Approved
ETHICS COMMITTEE, ST. THERESAS HOSPITAL, St. Theresas Hospital Sanath Nagar Opp Erragadda Raitu Bazar Hyderabad, Telangana - 500018 India
Approved
Institute Ethics Committee, Heritage Institute of Medical Science, NH-2, Bypass Road, Varanasi-221311, Uttar Pradesh, India
Approved
Institutional Ethics Committee, Baby Memorial Hospital, Indira Gandhi Road Puthiyara Post Kozhikode, Kozhikode,Kerala- 673004
Approved
Institutional Ethics Committee, C/O Principal Office, Christian Medical College and Hospital, Brown Road, Ludhiana -141008, Punjab, India
Approved
Institutional Ethics Committee, Governement Medical College and Attached Hospitals. Rangbari Road, Kota, Rajasthan - 324005
Approved
Institutional Ethics Committee, Government Medical College and Hospital, Nagpur Government Medical College, Medical Square Hanuman Nagar, Nagpur, Maharashtra - 440003 India
Approved
Institutional Ethics Committee, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, UP
Approved
Institutional Ethics Committee, Institute of Neurosciences Kolkata, AJC Bose Road, Kolkata, West Bengal – 700017, India
Approved
Institutional Ethics Committee, JSS Medical College and Hospital, Sri Shivarathreeshwara Nagar, Mysore, Karnataka - 570015
Approved
Institutional Ethics Committee, KG Hospital K. Govindaswamy Naidu Medical Trust, No 5, Government Arts College Road, Coimbatore, Tamil Nadu - 641018 India
Approved
Institutional Ethics Committee, KLE University KLE University KLE Dr.PK Hospital and MRC Nehru Nagar, Belagavi (Belgaum) Karnataka - 590010 India
Approved
Institutional Ethics Committee, PGIMS UHS Rohtak, Pt. BD Sharma, Post Graduate Institute of Sciences, Rohtak-124001, Haryana
Approved
Institutional Review Board of Sidhu Educational Research Institute & Hospital, G.T. Road, Doraha, Dist. Ludhiana-141421
Approved
IPGMEandR Resaerch Oversight Committee, IPGME and R, 244 Acharya J. C. Bose Road, Kolkata, West Bengal – 700020, India
Approved
Lalitha Super Specialities Hospital Ethics Committee, Kothapet, Guntur -522001. A.P.
Approved
Medanta Institutional Ethics Committee (MIEC), Medanta - The Medicity, Regulatory Office, 2nd Floor, Opposite Medical Library, Training Block, Sector-38, Gurgaon, Hariyana -122001
Approved
NewEra Hospital Ethics Committee, Central Avenue Road, Nera Telephone Exchange Chowk, Queta Colony, Near Jalaram Mandir, Nagpur - 440008
Approved
Nirmal Hospital Institutional Ethics committee Nirmal Hospital , Jhansi Opposite Gate No. 3 MLB Medical College Jhansi Jhansi Uttar Pradesh - 284128 India
Approved
Nirmal Hospital Institutional Ethics committee Nirmal Hospital , Jhansi Opposite Gate No. 3 MLB Medical College Jhansi Jhansi Uttar Pradesh - 284128 India
Approved
Postgraduate Institute of Medical Education and Research, Chandigarh, Institutional Ethics Committee, Room No- 6006, Sixth Floor, Research Block B, PGIMER, Chandigarh
Approved
Pushpanjali Hospital Ethics Committee, Pushpanjali Hospital & Research Center Pvt. ltd, Pushpanjali Palace, Delhi Gate, Agra -282002 U.P.
Scientific Research and Ethical Review Committee, Batra Hospital and Medical Research Centre, 1, Tughlakabad Institutional Area Mehrauli, Badarpur Road, New Delhi, 110062
(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) containing 30 mcg of Sovateltide
PMZ-1620 + Standard of care: Three doses of PMZ-1620 (Sovateltide), at 0.3 mcg/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 mcg/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
78.00 Year(s)
Gender
Both
Details
1. Adult males or females Aged 18 years through 78 years (have not had their 79th birthday).
2. Patient or Legally Acceptable Representative (LAR) 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
ExclusionCriteria
Details
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 more than or equal to 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
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
1. Proportion of patients with NIHSS score (more than and equal to 6), mRS score (more than and equal to 2) and BI score (Less than and equal to 60)
2. Proportion of patients with change in NIHSS score (more than and equal to 6), mRS score (more than and equal to 2) and BI score (more than and equal to 40) from baseline
3. Proportion of patients with overall clinical outcome as assessed by the global statistical test of NIHSS, mRS, and BI scores
1. On day 6, day 12, 1 month and 3 months post randomization
2. On day 6, day 12, 1 month and 3 months post randomization
3. On day 6, 1 month and 3 months post randomization
Secondary Outcome
Outcome
TimePoints
Change in Quality-of-life as assessed by EuroQol-EQ-5D.
At base line, 1 month, 2 months and 3 months post randomization
Proportion of patients with incidence in recurrent ischemic stroke
within 1 month and 3 months
Number of deaths occurs
within 3 months of post-randomization
Proportion of patients with radiographic or symptomatic Intra-Cerebral Hemorrhage (ICH)
within 24 (± 6) hours of randomization.
Change in MoCA score of patients
At 1 month and 3 months post-randomization
Proportion of patients with adverse events (AEs) and serious adverse events (SAEs)
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. PMID: 33428177; PMCID: PMC7872992.
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, Phase III efficacy study of PMZ-1620 therapy along with standard treatment in patients with acute ischemic stroke. A minimum of 132 patients (66 in each treatment arm) are to be evaluated as per the protocol, considering a discontinuation rate of about 20 %, a total of 158 patients (79 in each treatment arm) will be enrolled in the study. The enrolment period of the study will be approximately 15 months and the total duration of the study will be approximately 18 months. For an individual patient, the 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 + 2), visit 3 (Day 30 + 5), visit 4/telephonic visit (Day 60 ± 7), and visit 5/End of Study (Day 90 ± 7). At visit 1, a total of 158 patients will be randomized 1:1 into 2 treatment groups after meeting the eligibility criteria:
Group 1: PMZ-1620 + Standard treatment
Group 2: Normal Saline (Dose: Equal volume) + Standard treatment
PMZ-1620 or Normal Saline will be administered as an intravenous (IV) bolus over one minute within the window of 24 hours after the onset of stroke. In the PMZ group, three doses of PMZ-1620 (each dose of 0.3 μg/kg body weight) will be administered as an IV bolus over one minute at an interval of 3 hours ± 1 hour on day 1, day 3, and day 6 (total dose/day: 0.9 µg/kg body weight). In the control group, three doses of an equal volume of normal saline will be administered as an IV bolus over one minute at an interval of 3 hours ± 1 hour on day 1, day 3, and day 6 post-randomization. In both treatment groups, patients will be provided the standard treatment for stroke. Standard treatment to be provided to the patients shall be the one used in the particular hospital setup. Each patient will be monitored closely throughout his/her hospitalization for the qualifying stroke and will be followed for 3 months from randomization. Each patient will be assessed for efficacy parameters over 3 months from randomization.