Revacept in Symptomatic Carotid Stenosis

NCT01645306 | Completed Phase 2 Results DMC

• 1 other identifier: Revacept/CS/02
• Study Type: interventional
• Target: 158
• Locations: 2 countries
• Sites: 12

Brief Summary

Patients suffering from symptomatic carotid artery stenosis, transient ischemic attacks (TIAs), amaurosis fugax or stroke receive either Revacept (single dose) plus antiplatelet monotherapy or monotherapy alone. Patients receive a single dose of trial medication by intravenous infusion for 20 minutes. Patients are followed up one and three days after treatment, at 3 months and by a telephone interview at 12 months.

Conditions

Carotid Stenosis; Atherosclerosis; Stroke; Transient-ischaemic Attack; TIA; Amaurosis Fugax

Outcome Measures

Primary Outcomes (1)

• New DWI Lesion(s)

  The number of new diffusion weighted imaging (DWI) lesion(s) reported. (1 day after intervention compared to baseline).

  1 day post intervention

Other Outcomes (5)

• Patients With Any Stroke or Transient Ischemic Attack (TIA)

  90 days after IMP application

• Major Bleedings

  90 days after IMP application

• Any Clinical Event

  365 days after IMP application

Study Arms (3)

Phosphate buffered saline (PBS), 1% sucrose, 4% mannitol

PLACEBO COMPARATOR

Placebo control with PBS, 1% sucrose and 4% mannitol

Drug: Placebo

40 mg Revacept

ACTIVE COMPARATOR

low dose Revacept 40mg in PBS, 1% sucrose, 4% mannitol

Drug: Revacept

120 mg Revacept

ACTIVE COMPARATOR

high dose revacept 120mg in PBS, 1% sucrose, 4% mannitol

Drug: Revacept

Interventions

Revacept DRUG

single intravenous injection

Also known as: 40 mg or 120 mg

120 mg Revacept; 40 mg Revacept

Placebo DRUG

single intravenous injection

Also known as: Control Group

Phosphate buffered saline (PBS), 1% sucrose, 4% mannitol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Target population
• Diagnosis:
• Extracranial carotid artery stenosis (diagnosed by vascular duplex ultrasound peak flow or angiography)
• Lesions with ≥ 50 % stenosis according to the European Carotid Surgery Trial (ECST) criteria
• TIA, amaurosis fugax or stroke within the last 30 days
• Age and sex: Men and women aged \> 18 years Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after receiving investigational product in such a manner that the risk of pregnancy is minimised.

You may not qualify if:

• Sex and reproductive Status:
• WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for up to 4 weeks after receiving investigational product.
• Women who are pregnant or breastfeeding
• Women with a positive pregnancy test on enrollment or prior to investigational product administration.
• Target disease exceptions
• 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/ul), bleeding diathesis or coagulopathy (pathological international normalised ratio (INR) or activated partial thromboplastin time (aPTT))
• Thrombolysis within the last 48 hours
• Relevant haemorrhagic transformation as determined by CT, NMR or anamnesis
• Oral anticoagulation or dual anti-platelet therapy with aspirin or clopidogrel and other P2Y inhibitors at screening (3 days for dipyridamole extended release; 8 hours for tirofiban/Aggrastat)
• Sustained hypertension (systolic BP \> 179 mmHg or diastolic BP \>109 mmHg)

Sponsors & Collaborators

• AdvanceCor GmbH: lead

Study Sites (12)

Site 01: Department of Neurology, TU Munich

Munich, Bavaria, 81675, Germany

Location

Site 08: Universitätsklinikum Essen, Klinik für Neurologie

Essen, 45147, Germany

Location

Site 11: Universitätsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Site 07: Medizinische Hochschule Hannover, Klinik für Neurologie

Hanover, 30625, Germany

Location

Site 12: Universitätsklinikum Leipzig AöR

Leipzig, 04103, Germany

Location

Site 09: Universitätsmedizin Mainz, Klinik und Poliklinik für Neurologie

Mainz, 55131, Germany

Location

Site 04: Universitätsklinikum Tübingen, Klinik für Allgemeine Neurologie

Tübingen, 72076, Germany

Location

Site 06: Universitätsklinikum Ulm, Abteilung für Neurologie

Ulm, 89081, Germany

Location

Site 23 - University Hospital Coventry NHS Trust

Coventry, CV2 2DX, United Kingdom

Location

Site 26 - University College London Hospital

London, NW1 2BU, United Kingdom

Location

Site 28 - King's College London Hospital

London, SE5 8AF, United Kingdom

Location

Site 20: St George's NHS Trust

London, SW17 0QT, United Kingdom

Location

Related Publications (12)

• Bultmann A, Li Z, Wagner S, Peluso M, Schonberger T, Weis C, Konrad I, Stellos K, Massberg S, Nieswandt B, Gawaz M, Ungerer M, Munch G. Impact of glycoprotein VI and platelet adhesion on atherosclerosis--a possible role of fibronectin. J Mol Cell Cardiol. 2010 Sep;49(3):532-42. doi: 10.1016/j.yjmcc.2010.04.009. Epub 2010 Apr 27.

  PMID: 20430036 BACKGROUND

• Goertler M, Baeumer M, Kross R, Blaser T, Lutze G, Jost S, Wallesch CW. Rapid decline of cerebral microemboli of arterial origin after intravenous acetylsalicylic acid. Stroke. 1999 Jan;30(1):66-9. doi: 10.1161/01.str.30.1.66.

  PMID: 9880390 BACKGROUND

• Markus HS, Droste DW, Kaps M, Larrue V, Lees KR, Siebler M, Ringelstein EB. Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using doppler embolic signal detection: the Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) trial. Circulation. 2005 May 3;111(17):2233-40. doi: 10.1161/01.CIR.0000163561.90680.1C. Epub 2005 Apr 25.

  PMID: 15851601 BACKGROUND

• Massberg S, Konrad I, Bultmann A, Schulz C, Munch G, Peluso M, Lorenz M, Schneider S, Besta F, Muller I, Hu B, Langer H, Kremmer E, Rudelius M, Heinzmann U, Ungerer M, Gawaz M. Soluble glycoprotein VI dimer inhibits platelet adhesion and aggregation to the injured vessel wall in vivo. FASEB J. 2004 Feb;18(2):397-9. doi: 10.1096/fj.03-0464fje. Epub 2003 Dec 4.

  PMID: 14656994 BACKGROUND

• Molloy J, Markus HS. Asymptomatic embolization predicts stroke and TIA risk in patients with carotid artery stenosis. Stroke. 1999 Jul;30(7):1440-3. doi: 10.1161/01.str.30.7.1440.

  PMID: 10390320 BACKGROUND

• Nieswandt B, Watson SP. Platelet-collagen interaction: is GPVI the central receptor? Blood. 2003 Jul 15;102(2):449-61. doi: 10.1182/blood-2002-12-3882. Epub 2003 Mar 20.

  PMID: 12649139 BACKGROUND

• Ringelstein EB, Droste DW, Babikian VL, Evans DH, Grosset DG, Kaps M, Markus HS, Russell D, Siebler M. Consensus on microembolus detection by TCD. International Consensus Group on Microembolus Detection. Stroke. 1998 Mar;29(3):725-9. doi: 10.1161/01.str.29.3.725.

  PMID: 9506619 BACKGROUND

• Schonberger T, Siegel-Axel D, Bussl R, Richter S, Judenhofer MS, Haubner R, Reischl G, Klingel K, Munch G, Seizer P, Pichler BJ, Gawaz M. The immunoadhesin glycoprotein VI-Fc regulates arterial remodelling after mechanical injury in ApoE-/- mice. Cardiovasc Res. 2008 Oct 1;80(1):131-7. doi: 10.1093/cvr/cvn169. Epub 2008 Jun 19.

  PMID: 18566102 BACKGROUND

• Ungerer M, Rosport K, Bultmann A, Piechatzek R, Uhland K, Schlieper P, Gawaz M, Munch G. Novel antiplatelet drug revacept (Dimeric Glycoprotein VI-Fc) specifically and efficiently inhibited collagen-induced platelet aggregation without affecting general hemostasis in humans. Circulation. 2011 May 3;123(17):1891-9. doi: 10.1161/CIRCULATIONAHA.110.980623. Epub 2011 Apr 18.

  PMID: 21502572 BACKGROUND

• Jamasbi J, Megens RT, Bianchini M, Munch G, Ungerer M, Faussner A, Sherman S, Walker A, Goyal P, Jung S, Brandl R, Weber C, Lorenz R, Farndale R, Elia N, Siess W. Differential Inhibition of Human Atherosclerotic Plaque-Induced Platelet Activation by Dimeric GPVI-Fc and Anti-GPVI Antibodies: Functional and Imaging Studies. J Am Coll Cardiol. 2015 Jun 9;65(22):2404-15. doi: 10.1016/j.jacc.2015.03.573.

  PMID: 26046734 BACKGROUND

• Kleiman NS, Kolandaivelu K. Expanding the Roster: Developing New Inhibitors of Intravascular Thrombosis. J Am Coll Cardiol. 2015 Jun 9;65(22):2416-9. doi: 10.1016/j.jacc.2015.03.576. No abstract available.

  PMID: 26046735 BACKGROUND

• Uphaus T, Richards T, Weimar C, Neugebauer H, Poli S, Weissenborn K, Imray C, Michalski D, Rashid H, Loftus I, Rummey C, Ritter M, Hauser TK, Munch G, Groschel K, Poppert H. Revacept, an Inhibitor of Platelet Adhesion in Symptomatic Carotid Stenosis: A Multicenter Randomized Phase II Trial. Stroke. 2022 Sep;53(9):2718-2729. doi: 10.1161/STROKEAHA.121.037006. Epub 2022 Jun 13.

  PMID: 35695006 DERIVED

MeSH Terms

Conditions

Carotid Stenosis; Atherosclerosis; Stroke; Ischemic Attack, Transient; Amaurosis Fugax

Interventions

Revacept; Control Groups

Condition Hierarchy (Ancestors)

Carotid Artery Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Arteriosclerosis; Brain Ischemia; Blindness; Vision Disorders; Sensation Disorders; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Limitations and Caveats

The study was originally planned as primary endpoint study for the evaluation of reduction of micro-embolic signals (MES) by transcranial Doppler (TCD). Therefore MES incidence was a key inclusion criteria at screening. Due to low incidence of MES in this patient population with high screening failure rate the mandatory presence of MES was abandoned during the course of the study. Consecutively the study was changed to an explorative study of the same protocol specified endpoints.

Results Point of Contact

• Title: Prof. Dr. Götz Münch, CRP & CEO
• Organization: advanceCOR GmbH

muench@advancecor.com

+4989200020410

Study Officials

• Holger Poppert, Prof. Dr.

  Department of Neurology, TU Munich

  PRINCIPAL INVESTIGATOR

• Ian M Loftus, MD

  St George's NHS Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2012
• First Posted: July 20, 2012
• Study Start: March 8, 2013
• Primary Completion: October 5, 2018
• Study Completion: September 23, 2019
• Last Updated: January 28, 2021
• Results First Posted: January 28, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (8); GB (4)