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

Primary Purpose

Ischemic Stroke

Status

Unknown status

Phase

Phase 2

Locations

Moldova, Republic of

Study Type

Interventional

Intervention

THR-18

Placebo

Tissue Plasminogen Activator (tPA)

About this trial

This is an interventional treatment trial for Ischemic Stroke

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Municipal Emergency HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

THR-18

Placebo

Arm Description

Single administration of intravenous THR-18 solution

Single administration of intravenous THR-18 lookalike solution

Outcomes

Primary Outcome Measures

physical examination

ASPECTS score

ECASS-II bleeding grades

Severity of cerebral edema per computerized tomography according to the IST-3 grades

Final infarct volume per computerized tomography

Neurological deficits per the NIH stroke scale

Functional capacity per the modified Rankin Score

Change in blood levels of matrix metalloproteinase 9

heart rate

blood pressure

electrocardiogram

persons with adverse events

Secondary Outcome Measures

Full Information

NCT ID

NCT02572336

First Posted

October 3, 2015

Last Updated

November 16, 2015

Sponsor

D-Pharm Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT02572336

Brief Title

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

Official Title

Phase II Study to Assess the Safety, Imaging, Pharmacodynamic and Clinical Outcomes of Acute Ischemic Stroke Subjects Treated With tPA and THR-18

Study Type

Interventional

2. Study Status

Record Verification Date

October 2015

Overall Recruitment Status

Unknown status

Study Start Date

October 2015 (undefined)

Primary Completion Date

March 2016 (Anticipated)

Study Completion Date

April 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

D-Pharm Ltd.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ischemic Stroke

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

THR-18

Arm Type

Active Comparator

Arm Description

Single administration of intravenous THR-18 solution

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Single administration of intravenous THR-18 lookalike solution

Intervention Type

Drug

Intervention Name(s)

THR-18

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo is a THR-18 lookalike, to be administered with tPA.

Intervention Type

Drug

Intervention Name(s)

Tissue Plasminogen Activator (tPA)

Intervention Description

tPA is a thrombolytic agent. tPA is not an investigational drug.

Primary Outcome Measure Information:

Title

physical examination

Time Frame

30 days after administration

Title

ASPECTS score

Time Frame

2 days after administration

Title

ECASS-II bleeding grades

Time Frame

2 days after administration

Title

Severity of cerebral edema per computerized tomography according to the IST-3 grades

Time Frame

2 days after administration

Title

Final infarct volume per computerized tomography

Time Frame

30 days after administration

Title

Neurological deficits per the NIH stroke scale

Time Frame

30 days after administration

Title

Functional capacity per the modified Rankin Score

Time Frame

30 days after administration

Title

Change in blood levels of matrix metalloproteinase 9

Time Frame

3 days after administration

Title

heart rate

Time Frame

30 days after administration

Title

blood pressure

Time Frame

30 days after administartion

Title

electrocardiogram

Time Frame

30 days after administration

Title

persons with adverse events

Time Frame

30 days after administration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Gilad Rosenberg, MD

Phone

+972544474409

grosenberg@dpharm.com

Facility Information:

Facility Name

Municipal Emergency Hospital

City

Chisinau

Country

Moldova, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Prof. Stanslav Groppa, MD, PhD

12. IPD Sharing Statement

Learn more about this trial

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

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