The primary purpose of this study is to evaluate the safety and preliminary efficacy of microplasmin when administered intravenously to patients who have suffered an acute stroke within 12 hours before randomization.
While the primary objective of the trial is safety evaluation, efficacy assessments will also be obtained, including MRI/MRA (including DWI, PWI and T2 imaging) and plasma surrogate biomarkers. Clinical outcome will also be assessed at 7days, 30 days and 90 days post-treatment. At each of these visits, mortality and neurological assessments (NIHSS, Barthel index, mRankin scale) will be performed. In addition, vital status will be assessed vial a telephone contact at 60 days post-treatment.
The trial will investigate three dose regimens of microplasmin, all of which are within the range of doses previously evaluated in a Phase I trial in healthy volunteers; the planned sample size for the trial is approximately 40 patients.
The study will consist of 3 phases - the Baseline, In-hospital Phase and Follow up Phase. Baseline is from study entry through randomisation; the In-hospital phase is from treatment with study drug through hospital discharge or day 7, whichever occurs first. The follow up phase consists of visits to the hospital 30 days (+ 3 days) from the day of study drug administration. Hospital discharge is defined as the end of the discharge from the acute hospital setting. Discharge may be to home, to a rehabilitation setting or to a non-acute hospital setting.
- Microplasmin Drug
Intervention Desc: 1mg/kg bolus of placebo solution followed by 1,2 or 3mg/kg infusion of placebo solution ARM 1: Kind: Experimental Label: 1 ARM 2: Kind: Experimental Label: 2 ARM 3: Kind: Experimental Label: 3 ARM 4: Kind: Experimental Label: 4
- Allocation: Randomized
- Masking: Double Blind (Subject, Investigator)
- Purpose: Treatment
- Endpoint: Safety/Efficacy Study
- Intervention: Parallel Assignment
Trial will be conducted in 3 phases--the Baseline, In-hospital Phase and Follow up Phase. The first phase/Baseline will be from study through randomization, with an MRI at baseline, at 6 hours post-treatment and at 7 days after symptom onset. The In-hospital phase is from treatment with study drug (investigated in three dose regimens of microplasmin) or placebo through hospital discharge or day 7, whichever occurs first. The follow up phase consists of visits to the hospital 30 days (+ 3 days) from the day of study drug administration.
|Type||Measure||Time Frame||Safety Issue|
|Secondary||MR infarct size; recanalization on MRA; reperfusion on PWI; surrogate markers: MMP9, NSE; pharmacokinetics.|
|Primary||Intracranial haemorrhage||24 hours and Day-7||Yes|
|Primary||Change from Baseline in NIHSS||Day7 and Day-90||No|
|Secondary||Barthel Index and modified Rankin scale||Day-90||No|
|Secondary||Markers of systemic lysis||Baseline, end of treatment, 6, 12, 24, 72 and 96 hours||Yes|
- ThromboGenics Lead