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 tPA

Phase 1

Conditions: Acute ischemic stroke
MedDRA version: 14.1Level: PTClassification code 10061256Term: Ischaemic strokeSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2011-005317-37-AT

Lead Sponsor: Thrombotech Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 22

Inclusion Criteria

1) Male or female.
2) Diagnosis of acute ischemic stroke onset less than 3 hours prior to the planned start of intravenous tPA (alteplase).
3) Have suffered an acute hemispheric ischemic stroke, defined as acute, focal, neurological deficit(s), secondary to a presumed vascular event, which must include at least one of the following:
• At least one of the following components (as reflected by at least 1 point on any of the corresponding items of the NIHSS: 9, 3 or 11):
o Language dysfunction (aphasic disorder, excluding dysarthria)
o Visual field defect (excluding monocular blindness)
o Extinction and Inattention (formerly Neglect)
Or
• An indication on routine diffusion-weighted magnetic resonance imaging (DW-MRI) or computed tomography perfusion scan at screening /baseline that the acute stroke involves the cerebral cortex
4) NIHSS larger > 5 and < 18 for left and right hemisphere strokes.
5) Age 18-85 years both inclusive.
6) Signed informed consent from patient or legally authorized representative or an independent witness or an independent physician, if applicable according to the Details about the consent procedure described in country-specific supplements to this protocol.
7) Subjects are indicated for the application of intravenous tPA (alteplase).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

2) Time interval since stroke onset of less than 3 hours is impossible to determine with high degree of confidence.
3) Symptoms suggestive of subarachnoid haemorrhage, even if CT or MRI scan is negative for haemorrhage.
7) Neurological deficit that has led to stupor or coma (NIHSS level of consciousness score greater than or equal to 2).
8) High clinical suspicion of septic embolus.
9) Minor stroke with non-disabling deficit or rapidly improving neurological symptoms in the absence of major vessel occlusion.
10) Baseline NIHSS greater than 18 for left and right hemisphere strokes.
11) Evidence of acute or chronic ICH by head CT or MRI.
14) Persistent hypertension with systolic BP greater than 185 mmHg or diastolic BP greater than 110 mmHg (mean of 3 consecutive arm cuff readings over 20-30 minutes), not controlled by antihypertensive therapy or requiring nitroprusside for control.
15) Blood glucose greater than 200 mg/dl.
18) Have suffered a stroke within 90 days of the screening/baseline assessments that is either diagnostically confirmed or assumed to be in the same cerebral territory as is the current acute stroke.
32) Subjects with disabling congestive heart failure (CHF) or unstable angina.
34) Subjects that suffered a myocardial infarction in the last 90 days.
47) Have a positive urine pregnancy test at screening/baseline or be a lactating female.
48) Any condition that in the investigator’s judgement precludes participation in the study.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: Assess the feasibility of evaluation of the efficacy parameters following intravenous administration of two escalating doses (0.25 and 0.5 mg/kg, 150 ml) of THR-18 or placebo, infused as a 10% bolus over 2 minutes (15 ml) followed by a 60 min infusion of the remaining dose (135 ml), to acute ischemic stroke patients treated with tPA.;Main Objective: Assess the safety of intravenous administration of two escalating doses (0.25 and 0.5 mg/kg, 150 ml) of THR-18 or placebo, infused as a 10% bolus over 2 minutes (15 ml) followed by a 60 min infusion of the remaining dose (135 ml), to acute ischemic stroke patients treated with tPA.;Primary end point(s): The primary study variables will include the evaluation of the safety and elucidation of the PK profile of THR-18 in ischemic stroke subjects treated with tPA.;Timepoint(s) of evaluation of this end point: Throughout the whole study (safety parameters),<br>Day 1 (PK profile). <br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The secondary study variables include evaluation of the feasibility to use the efficacy parameters to detect an initial signal of efficacy.;Timepoint(s) of evaluation of this end point: 96-120 hours post drug administration, <br>day 30, <br>month 3,<br>depending on the endpoint.

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