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.

开始日期2015-10-01

申办/合作机构

Univo Pharmaceuticals Ltd.

NCT01957774 / Completed临床2期

Double-blind, Placebo-controlled, Escalating Single-dose, Phase 2a Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of THR-18 in Subjects With Acute Ischemic Stroke and Treated With tPA

The purpose of this study is to 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 bind to tPA and reduce its adverse effects without stopping tPA's breaking up of the blocking blood clot.
The primary purpose of this study is to evaluate the safety of THR-18 in acute ischemic stroke patients who are treated in parallel with tPA. Another purpose of this study is to investigate levels of THR-18 and tPA in the blood stream at different time points after they are injected, at the same time, into a vein. In addition, this study will measure tPA's effect on blood clot dissolution when tPA is given with and without THR-18. The study will also study the effect THR-18 may have on signals of brain damage that can be found in the blood after stroke: these signals of brain damage are small proteins called S100B and matrix metalloproteinase (MMP)-9. These proteins are released into the blood stream when the brain is injured.
The safety 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. Three doses of THR-18 will be tested, one after the other, in three groups of patients. In each group, some patients will receive THR-18 and some will receive placebo. This clinical study will be conducted only at one hospital in the Ukraine. In total, 30 patients are planned to participate in this study. These 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.

开始日期2013-10-01

申办/合作机构

Univo Pharmaceuticals Ltd.

NCT01253512 / Unknown status临床1/2期

Double Blind, Placebo Controlled, Escalating Single-dose, Pilot Study to Assess the Safety of THR-18 When Administered to Patients Suffering Acute Ischemic Stroke and Treated With Tissue Plasminogen Activator (tPA)

This will be a randomized, double-blind, placebo-controlled, multi-center, multi-national, escalating dose, pilot study comparing two doses of THR-18 to placebo when administered to patients suffering acute ischemic stroke and treated with Tissue Plasminogen Activator (tPA).
The study hypothesis is that THR-18 will be safe and well tolerated in subjects suffering acute ischemic stroke and treated with Thrombolysis.

开始日期2011-03-01

申办/合作机构

Thrombotech Ltd.

100 项与 THR-18 相关的临床结果

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100 项与 THR-18 相关的转化医学

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100 项与 THR-18 相关的专利（医药）

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项与 THR-18 相关的文献（医药）

2011-11-01·Neurological research4区 · 医学

THR-18, a 18-mer peptide derived from PAI-1, is neuroprotective and improves thrombolysis by tPA in rat stroke models

4区 · 医学

Article

作者: A Nimrod ; M Krakovsky ; A Higazi ; I Lamensdorf ; V Polianski ; R R Leker

OBJECTIVE:

The thrombolytic treatment of stroke is limited by a narrow therapeutic time window and is associated with significant adverse side effects. To improve this situation, the modulation of tissue-type plasminogen activator (tPA) activity by a synthetic plasminogen activator inhibitor-1-derived 18-mer peptide (THR-18) was examined in two models of stroke in rats.

METHODS:

In the first model (thromboembolic), stroke was induced by intra-carotid injection of micro-clots to rats, and tPA (6 mg/kg) was intravenously infused for 30 minutes with or without THR-18 (1 mg/kg) at 4 hours post-induction. In the second model [transient middle cerebral artery occlusion (tMCAO)], stroke was induced for 2 hours by a transient mechanical occlusion. tPA and/or THR-18 (0.02, 0.1, and 1 mg/kg) were intravenously infused for 60 minutes at the time of reperfusion.

RESULTS:

In the thromboembolic model, cerebral blood flow, measured before and up to 5.5 hours post-induction, revealed that tPA administration caused reperfusion of flow at 30 minutes post-infusion. Later on, an additional increase in reperfusion was seen in the tPA+THR-18 group, and not with tPA alone. In both models, the frequency of intracranial hemorrhage in the tPA-treated group was found to be significantly higher than the control, and this tPA effect was attenuated by THR-18. In the thromboembolic study, infarct size and brain edema were similar in the control and tPA-treated rats. However, the combination of tPA and THR-18 caused a statistically significant reduction in both parameters (infarct size 17.8 versus 25.0%, brain edema 5 versus 8%, tPA+THR-18 versus control, respectively). In the tMCAO mechanical model, infarct size and brain edema were both increased by tPA treatment as compared to the control group, and this increase was markedly diminished by THR-18 co-administration. Neurobehavioral assessment of the tMCAO animals performed at 72 hours post-stroke induction revealed significant improvements (P<0.05-0.01) in neuroscores in all groups of animals treated with peptide-tPA, as compared to the tPA monotherapy group. A significant (P<0.05) improvement in the neurological outcome was also seen in the THR-18 monoterapy group, as compared to the control animals, thus demonstrating a clear neuroprotective effect by the peptide on its own.

DISCUSSION:

The results support the use of THR-18 together with tPA in the thrombolytic therapy of stroke, in order to achieve better patency, less tPA-induced damage, and possibly a widening of tPA therapeutic time window.

100 项与 THR-18 相关的药物交易

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