Clinical Trials Register

Summary
EudraCT Number:	2011-001006-10
Sponsor's Protocol Code Number:	Revacept/CS/02
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-08-15
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2011-001006-10

A.3

Full title of the trial

REVACEPT, AN INHIBITOR OF PLATELET ADHESION IN SYMPTOMATIC CAROTID STENOSIS: A PHASE II, MULTICENTRE; RANDOMISED, DOSE-FINDING, DOUBLE-BLIND AND PLACEBO-CONTROLLED SUPERIORITY STUDY WITH PARALLEL GROUPS

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.3.2

Name or abbreviated title of the trial where available

Revacept/CS/02

A.4.1

Sponsor's protocol code number

Revacept/CS/02

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01645306

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	advanceCOR GmbH
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	advanceCOR GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	advanceCOR GmbH
B.5.2	Functional name of contact point	Münch
B.5.3	Address:
B.5.3.1	Street Address	Fraunhofer Straße 17
B.5.3.2	Town/ city	Martinsried
B.5.3.3	Post code	82152
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4989200020410
B.5.5	Fax number	+4989200020420
B.5.6	E-mail	muench@advancecor.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Revacept
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PR-15
D.3.9.2	Current sponsor code	Revacept
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.4
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients suffering from symptomatic carotid artery stenosis, transient ischemic attacks, amaurosis fugax or stroke and who presenting with microembolic signals.

E.1.1.1

Medical condition in easily understood language

Patients suffering from symptomatic carotid artery stenosis, transient ischemic attacks, amaurosis fugax or stroke and who presenting with microembolic signals.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	PT
E.1.2	Classification code	10007687
E.1.2	Term	Carotid artery stenosis
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Only patients who experienced a neurological event, including stroke, due to a narrowing of the main brain supplying artery, the carotid artery, will be included in the study. The study primarily investigates whether Revacept can reduce small blood clots caused by this narrowing of the carotid artery. These blood clots may cause a stroke or 'mini-strokes' called transient ischaemic attacks (TIAs), which can be early warning signs for a future stroke. These small blood clots are called micro-emboli and will be assessed by ultrasound of the smaller arteries to the brain, a technique in routine clinical practice called transcranial Doppler examination.

E.2.2

Secondary objectives of the trial

The disability or other functional defects after a stroke (NIH Stroke Scale) will be assessed by a clinical investigation or by direct questions. Directly after the treatment, small defects in the brain caused by small blood clots will be investigated by a magnetic resonance (MR) scan of the brain. Important clinical manifestations of the disease such as additional, future long lasting cerebral strokes, or short lasting neurological events (TIAs) will be assessed after 3 months. Additionally other sequelae of the underlying vessel disease will be monitored, including heart attacks, interventional treatment for other cario-vascular disease, or death due to such a disease. Patients will attend a follow up hospital visit at 3 months after treatment and be followed up by telephone interview 12 months after treatment.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Male and female patients aged >18 years
Diagnosis
•Extracranial carotid artery stenosis (diagnosed by vascular duplex ultrasound peak flow or angiography)
-Lesions with ≥ 50 % stenosis according to the European Carotis Surgery Trial (ECST) criteria
•MES detected by TCD (≥ 1 MES per hour)
•TIA, amaurosis fugax or stroke within the last 30 days

E.4

Principal exclusion criteria

Target disease exception

•NIHSS score > 18
•Recent intracerebral haemorrhage by X-ray computed tomography (CT) or nuclear magnetic resonance (NMR)
•Cardiac cause of embolisation (atrial fibrillation or other cardiac source e.g. artificial heart valves)
Medical history and concurrent disease
•History of hypersensitivity, contraindication or serious adverse reaction to inhibitors of platelet aggregation, hypersensitivity to related drugs (cross-allergy) or to any of the excipients in the study drug
•History or evidence of thrombocytopenia (<30.000/µl), bleeding diathesis or coagulopathy (pathological international normalised ratio (INR) or activated partial thrompoplastin time (aPTT))
•Thrombolysis within the last 48 hours
•Relevant haemorrhagic transformation as determined by CT, NMR or anamnesis
•Oral anticoagulation or dual antiplatelet therapy (aspirin combined with clopidogrel or other P2Y inhibitors) at screening; dipyridamole extended release within last 3 days; tirofiban/Aggrastat within the last 8 hours
•Sustained hypertension (systolic BP >179 mmHg or diastolic BP >109 mmHg)
•History of severe systemic disease such as terminal carcinoma, renal failure (or current creatinine >200 µmol/l), cirrhosis, severe dementia, or psychosis
•Current severe liver dysfunction (transaminase level greater than 5-fold over upper normal range limit)
•Active autoimmune disorder such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis or glomerulonephritis
•Known atrial fibrillation or other clinically significant ECG abnormalities (at presentation)

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is to evaluate whether the incidence of microembolic signals (MES) can be reduced in patients with symptomatic carotid artery stenosis who have been treated with Revacept plus antiplatelet monotherapy (aspirin or clopidogrel) versus antiplatelet monotherapy alone (placebo). MES will be assessed by transcranial Doppler (TCD) examination.

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline to 1-2 days after treatment.

E.5.2

Secondary end point(s)

•Rate of MES per hour (before and after treatment)
•Assessment of neurological status (NIH Stroke Scale)
•Cerebral lesion analysis by DWI-NMR and correlation to neurological status (before and after treatment)
•Clinical endpoints will be summarised cumulatively i.e. before treatment, 1 and 3 days after treatment, at 3 months and at 12 months. The following endpoints will be recorded:
oRate of all cause death
oRate of stroke-related death
oAny TIA, amaurosis fugax or stroke including haemorrhagic stroke
•Assessment of cardiovascular outcome including myocardial infarction and re-intervention up to 3 and 12 months

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline to 3 months / 12 months.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1