A Study of the Safety, Imaging and Clinical Outcomes of THR-18 in Acute Stroke Subjects Treated With tPA
A Study of the Safety, Imaging and Clinical Outcomes of THR-18 in Acute Stroke Subjects Treated With tPA
This study will test the experimental drug "THR-18" given together with the drug "tissue
 plasminogen activator" for the treatment of stroke. Tissue plasminogen activator is also
 called "tPA".

 Strokes often result from blockade of blood supply caused by blood clots forming within the
 blood vessel feeding the brain. Such strokes are called "Ischemic strokes". Treatment of
 these strokes is aimed at breaking up the blood clot(s) and renewing the blood flow before
 further parts of the brain die. Breaking up the blood clot is possible with the drug tPA when
 it is injected into a vein shortly after the stroke starts. However, along with breaking up
 the blood clot, tPA sometimes causes adverse effects, for example, it may cause bleeding.
 THR-18, the drug tested in this study, is meant to reduce tPA's adverse effects without
 stopping tPA's breaking up of the blocking blood clot.

 The aims of this study are to evaluate the safety of THR-18 in acute ischemic stroke patients
 who are treated in parallel with tPA, to measure tPA's effect on blood clot dissolution when
 this drug is given with and without THR-18, and to study the effects THR-18 may have on
 signals of brain damage as seen on brain computerized tomography (a type of brain x-ray)
 after treatment with tPA with and without THR-18. Patients will also be evaluated for their
 ability to perform daily activities after the stroke following tPA treatment with and without
 THR-18.

 The evaluation of THR-18 in this study will be done in comparison to placebo. Placebo is a
 drug that looks exactly like THR-18 but has no activity. One dose of THR-18 will be tested,
 in 20 patients. In parallel, 20 other patients will receive placebo. In total, 40 patients
 are planned to participate in this study. The decision whether a patient will receive THR-18
 or placebo will be based on chance (this procedure is called "randomization"). This clinical
 study will be conducted only at one hospital, in the Republic of Moldova. The patients will
 be in the hospital for at least 3 days after receiving the study treatment. Then, about 1
 month later, they will be invited for a last follow-up visit.
Inclusion Criteria:

 -  Age 18 to 80 years, both inclusive.

 -  Acute ischemic stroke, defined as an acute, focal, neurological deficit(s), secondary
 to an ischemic vascular event, which must include at baseline at least 1 of the
 following components as reflected by at least 1 point on items 9, 3 and 11 of the
 National Institutes of Health Stroke Scale (NIHSS), i.e. language dysfunction (aphasic
 disorder, excluding dysarthria), visual field defect (excluding monocular blindness),
 extinction and inattention.

 -  NIHSS above 5 and below 18 for left and right hemisphere strokes.

 -  Indication for the administration of intravenous tPA for acute stroke in accordance
 with tPA's authorized label for acute stroke.

 -  Pre-stroke modified Rankin Scale score lower or equal to 2.

 -  Ability to understand the requirements of the study and willing to provide written
 informed consent. In the event of incapacitated subjects, informed consent will be
 sought from a legally acceptable representative or by any other means as approved by
 the Ethics Committee.

 -  No contraindication to i.v. administration of iodinated contrast agent

 Exclusion Criteria:

 -  Contraindications for tPA administration because of an increased risk of bleeding

 -  Known hypersensitivity to tPA or to iodinated contrast agents.

 -  Neurological deficit that has led to stupor or coma (NIHSS level of consciousness
 score above or equal to 2).

 -  Stroke 90 days before screening/baseline assessments that is either confirmed or
 assumed to be in the same cerebral territory as is the current acute stroke.

 -  Seizure any time between stroke symptoms onset and randomization.

 -  Life expectancy below 1 month.

 -  Serious illness, e.g. heart failure grade III or IV according to the New York Heart -
 Association functional classification, severe hepatic or renal failure.

 -  Neurological or non-neurological disease that in the investigator's opinion may
 confound the assessment of the treatment's safety or biological effects.

 -  Estimated creatinine clearance equal to or lower than 45 mL/min or dependency on renal
 dialysis.

 -  Treatment of the qualifying stroke with intravenous heparin unless activated partial
 thromboplastin time prolongation is not more than 2 seconds above the upper limit of
 normal for local laboratory prior to study drug initiation.

 -  Treatment of the qualifying stroke with a low molecular weight heparin or heparinoid.

 -  Female of childbearing potential who is not willing to use adequate and effective
 birth control measures for the duration of the trial.

 -  Positive urine pregnancy test at screening/baseline or lactating female.

 -  Body weight (measured or estimated) above 100 kg.

 -  Current drug or alcohol abuse.