A Prospective, Multicentric, Randomized, Double Blind, Parallel, Saline ControlledPhase II Clinical Study to Compare the Safety and Efficacy of PMZ-1620 Therapy alongwith Standard Supportive Care in Subjects of Acute Ischemic Stroke.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 7
- 主要终点
- Proportion of subjects with adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 70.00 Year(s)（—）
- 性别
- All
入选标准
- •Adult males or females Aged 18 years through 70 years (have not had their 71st birthday)
- •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.
- •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).
- •No hemorrhage as proved by cerebral CT/MRI scan.
- •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.
- •Subjects receiving thrombolytic therapy.
- •Reasonable expectation that subject will receive standard post stroke physical, occupational, speech, and cognitive therapy as indicated.
- •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.
排除标准
- •Subjects receiving endovascular therapy
- •Subjects presenting with lacunar, hemorrhagic and/or brain stem stroke.
- •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).
- •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).
- •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.
- •Known valvular heart disease with CHF in the last 6 months.
- •Known (or in the Investigator’s clinical judgment) existence of severe aortic stenosis or mitral stenosis.
- •Cardiac surgery involving thoracotomy (e.g., coronary artery bypass graft, (CABG), valve replacement surgery) in the last 6 months.
- •Subject is a candidate for any surgical intervention for treatment of stroke which may include but not limited to endovascular techniques.
- •Subjects who are obese, body mass index (BMI) > 30 and/or on hormonal contraceptives.
- •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.
- •Patient has systolic BP < 90 mmHg or > 220 mmHg or diastolic BP < 40 mmHg or > 130 mmHg.
- •Acute myocardial infarction in the last 6 months.
- •Signs or symptoms of acute myocardial infarction, including electrocardiogram findings, on admission.
- •Concomitant treatment with neuroprotective or nootropic drugs (e.g. piracetam, citicoline, investigational, neuroprotective substances).
- •Qualitative estimation of troponin on admission.
- •Suspicion of aortic dissection on admission.
- •Acute arrhythmia (including any tachy- or bradycardia) with hemodynamic instability on admission (systolic BP < 100 mmHg).
- •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.
- •Current acute or chronic lung disease requiring supplemental chronic or intermittent oxygen therapy.
- •Serum creatinine > 2.0 mg/dL or 180 μmol/L.
- •Severe chronic anemia (hemoglobin < 7.5 g/dL).
- •Pregnancy, breastfeeding or positive pregnancy test.
- •(Women of childbearing age must have a negative pregnancy test prior to study drug administration).
- •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 subject.
结局指标
主要结局
Proportion of subjects with adverse events (AEs) and serious adverse events (SAEs)
时间窗: 3 Months
次要结局
- 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.)
- 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.)