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PMZ-1620 (Sovateltide) in Acute Ischemic Stroke Patients

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ClinicalTrials.gov Identifier: NCT04046484
Recruitment Status : Completed
First Posted : August 6, 2019
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
Pharmazz, Inc.

Tracking Information
First Submitted Date  ICMJE July 31, 2019
First Posted Date  ICMJE August 6, 2019
Last Update Posted Date August 14, 2019
Actual Study Start Date  ICMJE January 19, 2018
Actual Primary Completion Date April 12, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 5, 2019)
  • Incidence of PMZ-1620 related adverse events [ Time Frame: 90 days ]
    The primary objective of the study is to determine incidence of drug (PMZ-1620) related adverse events.
  • Number of patients not receiving full treatment [ Time Frame: 90 days ]
    Tolerability will be determined by the number of patients that do not receive all the 9 doses of PMZ-1620.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04046484 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2019)
  • Change in National Institute of Health Stroke Scale (NIHSS) [ Time Frame: 90 days ]
    To determine whether PMZ-1620 therapy over and above standard of care increases the proportion of ischemic stroke subjects with National Institute of Health Stroke Scale (NIHSS) score ≥ 6 score at 3 months. NIHSS is 42 point scale where 0 is the best o and 42 is the worst outcome.
  • Change in modified Rankin Scale (mRS) [ Time Frame: 90 days ]
    Neurological outcome as assessed by modified Rankin Scale (mRS) score ≤ 2 at 3 months 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] [ 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.
  • Change in EuroQol [ Time Frame: 90 days ]
    Quality-of-life (QoL) as assessed by EuroQol at 3 months post randomization. European quality of life 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) [ Time Frame: 90 days ]
    Stroke-Specific Quality of Life (SSQOL) at 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 [ 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 (QVSFS)
  • Incidence of mortality [ Time Frame: 90 days ]
    Incidence of mortality within 3 months post randomization
  • Incidence of Intra-Cerebral Hemorrhage (ICH) [ Time Frame: 30 hours ]
    Incidence of symptomatic Intra Cerebral Hemorrhage (ICH) within 24 (± 6) hours of randomization
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PMZ-1620 (Sovateltide) in Acute Ischemic Stroke Patients
Official Title  ICMJE 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
Brief Summary This was a prospective, multicentric, randomized, double blind, parallel, saline controlled Phase II clinical study to compare the safety and efficacy of PMZ-1620 (INN: Sovateltide) therapy along with standard supportive care in patients of acute ischemic stroke.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • Acute Stroke
  • Cerebral Ischemia
Intervention  ICMJE
  • Drug: Normal Saline along with standard treatment
    The arm is for active comparison for PMZ-1620 (sovateltide), 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. Normal saline (vehicle) with standard treatment will be provided.
    Other Name: Vehicle
  • Drug: PMZ-1620 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: Sovateltide (IRL-1620) along with standard treatment
Study Arms  ICMJE
  • Active Comparator: Normal Saline (Dose: Equal volume) + 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.
    Intervention: Drug: Normal Saline along with standard treatment
  • Experimental: PMZ-1620 + 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).
    Intervention: Drug: PMZ-1620 along with standard treatment
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 5, 2019)
40
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 30, 2019
Actual Primary Completion Date April 12, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  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 upto 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:

    • Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) or,
    • 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

Exclusion Criteria:

  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, neuroprotecti-ve 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE India
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04046484
Other Study ID Numbers  ICMJE PMZ-01 Version 2.0/18
CTRI/2017/11/010654 ( Registry Identifier: Clinical Trials Registry - India )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Results will be communicated and published as manuscript
Responsible Party Pharmazz, Inc.
Study Sponsor  ICMJE Pharmazz, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Anil Gulati Pharmazz, Inc.
PRS Account Pharmazz, Inc.
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP