A Study of the Safety, Imaging and Clinical Outcomes of THR-18 in Acute Stroke Subjects Treated With tPA

Recruiting

Phase 2 Results N/A

Trial Description

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.

Conditions

Interventions

  • Placebo Drug
    Intervention Desc: Placebo is a THR-18 lookalike, to be administered with tPA.
    ARM 1: Kind: Experimental
    Label: Placebo
    Description: Single administration of intravenous THR-18 lookalike solution
  • THR-18 Drug
    Intervention Desc: THR-18 is an 18-mer peptide derived from the sequence of human plasminogen activator inhibitor 1 (PAI-1), having the ability to bind to a site of tissue plasminogen activator (tPA) distal to its catalytic site and uncouple the beneficial clot-dissolving properties of tPA from its deleterious non-fibrinolytic effects.
    ARM 1: Kind: Experimental
    Label: THR-18
    Description: Single administration of intravenous THR-18 solution
  • Tissue Plasminogen Activator (tPA) Drug
    Intervention Desc: tPA is a thrombolytic agent. tPA is not an investigational drug.
    ARM 1: Kind: Experimental
    Label: THR-18
    Description: Single administration of intravenous THR-18 solution
    ARM 2: Kind: Experimental
    Label: Placebo
    Description: Single administration of intravenous THR-18 lookalike solution

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
  • Purpose: Treatment
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary physical examination 30 days after administration Yes
Primary ASPECTS score 2 days after administration No
Primary ECASS-II bleeding grades 2 days after administration No
Primary Severity of cerebral edema per computerized tomography according to the IST-3 grades 2 days after administration No
Primary Final infarct volume per computerized tomography 30 days after administration No
Primary Neurological deficits per the NIH stroke scale 30 days after administration No
Primary Functional capacity per the modified Rankin Score 30 days after administration No
Primary Change in blood levels of matrix metalloproteinase 9 3 days after administration No
Primary heart rate 30 days after administration Yes
Primary blood pressure 30 days after administartion Yes
Primary electrocardiogram 30 days after administration Yes
Primary persons with adverse events 30 days after administration Yes

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