Efficacy and Safety Trial With S 44819 After Recent Ischemic Cerebral Event

Randomized Efficacy and Safety Trial With Oral S 44819 After Recent Ischemic Cerebral Event. International, Multi-centre, Randomized, Doubleblind Placebo-controlled Phase II Study. (RESTORE BRAIN Study)

The purpose of this study is to assess the efficacy and safety of S 44819 in enhancing functional recovery after an ischemic stroke.

Study Overview

• Status: Completed
• Conditions: Post Stroke Recovery
• Intervention / Treatment: Drug: S 44819 150 mg twice a day; Drug: S 44819 300 mg twice a day; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 585
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Royal Adelaide Hospital Department of Neurology
  • Birtinya, Australia, 4575
    • Sunshine Coast hospital
  • Clayton, Australia, 3168
    • Monash Medical Centre Department of Neurology
  • Elizabeth Vale, Australia, 5112
    • Lyell McEwin Hospital Neurology Department
  • Gosford, Australia, 2250
    • Gosford Hospital Neurosciences Department
  • Heidelberg, Australia, VIC 3084
    • Austin Health Neurology Department
  • Herston, Australia, 4029
    • Royal Brisbane & Women's Hospital Department of Neurology
  • Melbourne, Australia, 3004
    • Alfred Health
  • Parkville, Australia, 3050
    • Royal Melbourne Hospital Department of Neurology
  • Southport, Australia, QLD 4215
    • Gold Coast University Hospital
• Belgium
  • Brugge, Belgium, 8000
    • AZ. St. Jan
  • Brugge, Belgium, 8000
    • AZ Sint-Lucas Neurologie
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
  • Hasselt, Belgium, 3500
    • Jessa Ziekenhuis Dienst Neurologie
  • Leuven, Belgium, 3000
    • Uz Leuven Campus Gasthuisberg
  • Liege, Belgium, 4000
    • Les Cliniques Saint-Joseph
  • Tielt, Belgium, 8700
    • Sint Andries Ziekenhuis Dienst Neurologie
• Brazil
  • Botucatu, Brazil, 18618-970
    • Hospital das Clínicas da Faculdade de Medicina de Botucatu
  • Joinville, Brazil, 89202-165
    • Clinica Neurológica e Neurocirúrgica de Joinville
  • Matão, Brazil, 15990-000
    • Hospital Carlos Fernando Malzone Departamento de Neurologia
  • Porto Alegre, Brazil, 90110-270
    • IMV Pesquisa Neurológica Setor de Pesquisa Clinica
  • Porto Alegre, Brazil, 90610-000
    • Hospital Sao Lucas da Pontificia Universidade Catolica RS Setor de Pesquisa Clínica
  • Ribeirao Preto, Brazil, 14015-130
    • Hospital das Clinicas da Fac. de Med. de Ribeirao Preto Unidade de Emergencia - Centro de Estudo
  • Ribeirão Preto, Brazil, 14015-130
    • Hospital das Clinicas da Fac. de med. de Ribeirao Preto Unidade de Emergiancia
  • Rio de Janeiro, Brazil, 20941-150
    • Hospital Quinta D'or Departamento de Neurologia
  • Sao Paulo, Brazil, 01221-020
    • Irmandade Santa Casa de Misericordia de Sao Paulo Ambulatório de Neurologia
  • Sao Paulo, Brazil, 04039-032
    • UNIFESP - Universidade Federal de Sao Paulo Centro de Pesquisa em Neurologia
• Canada
  • Edmonton, Canada, T6G 2G3
    • University of Alberta
  • Greenfield Park, Canada, J4V 2H1
    • Charles LeMoyne Hospital-CISSS de la Monteregie-Centre
  • Montreal, Canada, H3G 1A4
    • Montreal General Hospital
  • Saint John, Canada, E2L 4L2
    • Saint John Regional Hospital
• Czechia
  • Brno, Czechia, 625 00
    • Fakultní nemocnice Brno Neurologická klinika
  • Brno, Czechia, 656 91
    • Fakultni nemocnice u sv. Anny Neurologicka klinika
  • Jihlava, Czechia, 586 33
    • Nemocnice Jihlava
  • Praha, Czechia, 128 08
    • Vseobecna fakultni nemocnice II. interni klinika VFN a 1. LF UK
• France
  • Bordeaux, France, 33076
    • CHU Bdx-Hôpital Pellegrin-Tripode Service de Neurologie
  • Corbeil-essonnes, France, 91106
    • Hôpital Sud-Francilien Unité Neurovasculaire
  • Creteil, France, 94010
    • CHU Henri Mondor Service de Neurologie
  • Le Kremlin-Bicêtre, France, 94270
    • CHU de Bicêtre Service de neurologie
  • Lille, France, 59037
    • CHRU-Hôpital Roger Salengro Service de Neurologie
  • Montpellier, France, 34295
    • CHU-Hôpital Gui de Chaulliac Unité de Neuropshysiologie Clinique
  • Paris, France, 75010
    • Hôpital Lariboisière, Fernand-Vidal Service de Neurologie
  • Paris, France, 75674
    • Hôpital Sainte-Anne Service de Neurologie
  • Poitiers, France, 86021
    • CHU-Hôpital de la Milétrie Service de Neurologie
• Germany
  • Altenburg, Germany, 04600
    • Klinikum Altenburger Land GmbH Neurologische Klinik
  • Bad Neustadt An Der Saale, Germany, 97616
    • Neurologische Klinik GmbH, Bad Neustadt
  • Berlin, Germany, 12351
    • Vivantes Klinikum Neukölln Klinik für Neurologie mit Stroke Unit
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen Neurologische Klinik
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen Neurologische Universitätsklinik Essen
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Klinik und Poliklinik für
  • Minden, Germany, 32429
    • Johannes Wesling Klinik Minden Klinik für Neurologie
  • Siegen, Germany, 57076
    • Kreisklinikum Siegen Klinik fuer Neurologie
  • Tübingen, Germany, 72076
    • Universitätsklinik der Eberhard-Karls Universtiät Tübingen Hertie-Institut für Klinische Hirnforschung
  • ULM, Germany, 89081
    • Universitätsklinikum Ulm Neurologische Klinik (RKU)
• Hungary
  • Budapest, Hungary, 1145
    • Országos Idegsebészeti Tudományos Intézet
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem Neurologiai Klinika
  • Budapest, Hungary, 1106
    • Bajcsy-Zsilinszky Korhaz es Rendelointezet Neurologiai Osztaly
  • Budapest, Hungary, 1125
    • Szent Janos Korhaz Neurologiai osztaly
  • Budapest, Hungary, 1134
    • Honved Korhaz Stroke reszleg
  • Gyor, Hungary, 9024
    • Petz Aladar Megyei Oktato Korhaz Neurologiai Osztaly
  • Kaposvár, Hungary, 7400
    • Somogy Megyei Kaposi Mor Oktato Korhaz Neurologiai Osztaly
  • Kistarcsa, Hungary, 2143
    • Flor Ferenc Korhaz Neurologia
  • Miskolc, Hungary, 3526
    • B-A-Z Megyei Korhaz es Egyetemi Oktato Korhaz Stroke, Er- es Neurologiai, Toxikologiai Osztaly
  • Nagykanizsa, Hungary, 8800
    • Kanizsai Dorottya Korhaz Neurologiai Osztaly
  • Nyiregyhaza, Hungary, 4400
    • Josa Andras Oktatokorhaz Neurologiai Osztaly
  • Pecs, Hungary, 7623
    • Pecsi Tudomanyegyetem Klinikai Kozpont Neurologiai Klinika
  • Sopron, Hungary, 9400
    • Soproni Erzsebet Oktato Korhaz Neurologiai Osztaly
  • Szeged, Hungary, 6725
    • Szegedi Tudomanyegyetem Szent-Gyorgy Albert Klinikai Kozpont
• Italy
  • Lecce, Italy, 73100
    • Vito FAZZI U.O. semplice Stroke Unit
  • Milano, Italy, 20132
    • Ospedale San Raffaele
  • Milano, Italy, 20123
    • Ospedale San Giuseppe UOC di Neurologia e Stroke Unit
  • Negrar, Italy, 37020
    • Ospedale Sacro Cuore Don Calabria Negrar NEUROLOGY DEPT
  • Pozzilli, Italy, 86077
    • Istituto Neurologico mediterraneo NEUROMED Dipartimento di Medicina Riabilitativa e Specialistica Repar
  • Rome, Italy, 00161
    • Policlinico Umberto I Emergency Department Stroke Unit
• Korea, Republic of
  • Busan, Korea, Republic of, 47392
    • Inje University Busan Paik Hospital
  • Busan, Korea, Republic of, 49201
    • Dong-A University Medical Center Department of Neurology
  • Daegu, Korea, Republic of, 41944
    • Kyungpook National University Hospital Department of Neurology
  • Gwangju, Korea, Republic of, 61469
    • Chonnam National University Hospital Department of Neurology
  • Seongnam, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital Department of Orthopaedic
  • Seoul, Korea, Republic of, 02447
    • Kyung Hee University Hospital
  • Seoul, Korea, Republic of, 05505
    • ASAN Medical Center Department of Neurology
• Netherlands
  • Heerlen, Netherlands, 6419 PC
    • Zuyderland Medisch Centrum Afdeling Neurologie
  • Nijmegen, Netherlands, 6525 GA
    • UMC St Radboud Afdeling Neurologie
  • Nijmegen, Netherlands, 6532 SZ
    • Canisius Wilhelmina Ziekenhuis Afdeling Neurologie
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus MC Afdeling Neurologie
  • Zwolle, Netherlands, 8011 JW
    • Isala Klinieken Afdeling Neurologie
• Poland
  • Chelm, Poland, 22-100
    • Samodzielny Publiczny Wojewodzki Szpital Specjalistyczny Oddzial Neurologiczny i Oddzial Udarowy
  • Gdansk, Poland, 80-803
    • M. Kopernika Provincial Specialist Hospital Dpt of Neurology
  • Katowice, Poland, 40-635
    • Samodzielny Publiczny Szpital Kliniczny nr7 SUM w Katowicach Oddzial Neurologii z Pododdzialem Udarowym
  • Konskie, Poland, 26-200
    • Szpital Specjalistyczny sw. Lukasza Oddzial Neurologii i Oddzial Udarowy
  • Lodz, Poland, 93-113
    • Miejskie Centrum Medyczne Jonscher Szpital Dr K. Jonschera
  • Lublin, Poland, 20-954
    • Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie Oddzial Neurologii
  • Rybnik, Poland, 44-200
    • Wojewodzki Szpital Specjalistyczny SPZOZ nr 3 w Rybniku
  • Sandomierz, Poland, 27-600
    • Szpital Specjalistyczny Ducha Swietego w Sandomierzu Oddzial Neurologii
  • Warszawa, Poland, 02-957
    • Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
• Spain
  • Albacete, Spain, 02006
    • H. General de Albacete Servicio de Neurología
  • Badalona, Spain, 08916
    • H. Germans Trias I Pujol Servicio de Neurología
  • Barcelona, Spain, 08003
    • H. del Mar Neurología
  • Barcelona, Spain, 08035
    • H. Valle de Hebrón Servicio de Neurología
  • Barcelona, Spain, 08036
    • H. Clinic de Barcelona Comprehensive Stroke Center
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge Servicio de Neurología-Unidad de Ictus-Planta 9
  • Girona, Spain, 17007
    • H. Josep Trueta Servicio de Neurología
  • Madrid, Spain, 28006
    • H. Universitario La Princesa Servicio de Neurología
  • Madrid, Spain, 28034
    • H. Ramón y Cajal Servicio de Neurología
  • San Sebastian, Spain, 20080
    • H. Universitario de Donosti Servicio de Neurología
  • Sevilla, Spain, 41013
    • H. Virgen del Rocío Servicio de Neurología
  • Valencia, Spain, 46026
    • Hospital Universitario La Fe Servicio de Neurología
• Sweden
  • Hassleholm, Sweden, 281 25
    • Hassleholms Sjukhus Stroke- och rehabiliteringsavdelningen 9
  • Linkoping, Sweden, 581 85
    • University Hospital Department of Neurology
  • Skovde, Sweden, 541 85
    • Skaraborgs Sjukhus Skovde Strokenheten
  • Stockholm, Sweden, 182 88
    • Danderyds Sjukhus Medicinmottagningen
  • Uppsala, Sweden, 751 85
    • Akademiska Sjukhuset Strokeavdelningen 85B
• United Kingdom
  • Bath, United Kingdom, BA1 3NG
    • Royal United Hospital Older People's Unit
  • Glasgow, United Kingdom
    • Queen Elizabeth University Hospital
  • Harrow, United Kingdom, HA1 3UJ
    • Northwick Park Hospital Neurology
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary Dpt of Neurology
  • London, United Kingdom, SW17 0QT
    • St George's University Hospitals Stroke Research office
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital
  • Poole, United Kingdom, BH15 2JB
    • Poole NHS Foundation Trust Stroke Unit
  • Sheffield, United Kingdom, S10 2JF
    • Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
  • Stoke on Trent, United Kingdom, ST4 6QG
    • Royal Stoke University Hospital Stroke Team Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Patients aged between 18 and 85 years (both inclusive)
• Acute ischemic stroke that occured between 72 hours (3 days) and 192 hours (8 days) (both inclusive) before inclusion

Exclusion criteria :

• Any non-selection criteria, which could have occurred after the selection visit
• Positive urinary or blood pregnancy test (for female patients of child bearing potential)
• Any clinically significant findings from the local laboratory test likely to interfere with the ability to participate in the study and / or with the study outcome
• Severe renal impairment detected in the local laboratory test
• Severe hepatic impairment or liver enzymes abnormalities found in the local laboratory test
• Stroke due to cerebral venous thrombosis
• Brain MRI showing a severe microangiopathy
• Brain imaging showing an acute haemorrhagic stroke or a symptomatic haemorrhagic transformation of the brain infarct
• Qualifying ischemic cerebral event older than 192 hours at inclusion
• Any clinically relevant abnormalities detected during the examinations likely to interfere with study procedures or study outcome,
• Repeated prolongation of ECG QTcF
• Patient or authorised representative refusing to attend study visits or to take part in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Two sachets of placebo twice a day
Experimental: S 44819 150 mg twice a day	Drug: S 44819 150 mg twice a day; One sachet of S 44819 150 mg and one sachet of placebo twice a day
Experimental: S 44819 300 mg twice a day	Drug: S 44819 300 mg twice a day; Two sachets of S 44819 150 mg twice a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Modified Rankin Scale (mRS)	Up to 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
National Institutes of Health Stroke Scale (NIHSS) total score	Efficacy criterion	Selection visit Day 0 Day 5 Day 30 Day 60 Day 90 Day 105
Barthel Index (BI) total score	Efficacy criterion	Day 30 Day 60 Day 90 Day 105
Montreal Cognitive Assessment scale (Moca) total score	Efficacy criterion	Day 30 Day 90
Trail Making Test (TMT) time for part A	Efficacy criterion	Day 30 Day 90
Adverse events	Safety criterion	Through study completion, an average of 3 months
Suicidal ideation and suicidal behavior using the Columbia-Suicide Severity Rating Scale (C-SSRS)	Safety criterion	Day 5 Day 30 Day 60 Day 90 Day 105
Body weight	Safety criterion	Selection visit Day 30 Day 60 Day 90 Day 105
Vital signs (supine for Systolic and Diastolic Blood Pressure)	Safety criterion	Selection visit Day 0 Day 5 Day 30 Day 60 Day 90 Day 105
12 lead-ECG	Safety criterion	Day 0 Day 5 Day 30 Day 60 Day 90 Day 105
Trail Making Test (TMT) time for part B	Efficacy criterion	Day 30 Day 90

Collaborators and Investigators

• Sponsor: Institut de Recherches Internationales Servier
• Collaborators: ADIR, a Servier Group company

Publications and helpful links

General Publications

• Chabriat H, Bassetti CL, Marx U, Picarel-Blanchot F, Sors A, Gruget C, Saba B, Wattez M, Audoli ML, Hermann DM. Randomized Efficacy and Safety Trial with Oral S 44819 after Recent ischemic cerebral Event (RESTORE BRAIN study): a placebo controlled phase II study. Trials. 2020 Feb 3;21(1):136. doi: 10.1186/s13063-020-4072-2.
• Chabriat H, Bassetti CL, Marx U, Audoli-Inthavong ML, Sors A, Lambert E, Wattez M, Hermann DM; RESTORE BRAIN study investigators. Safety and efficacy of GABAA alpha5 antagonist S44819 in patients with ischaemic stroke: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2020 Mar;19(3):226-233. doi: 10.1016/S1474-4422(20)30004-1.

Helpful Links

• Results Summary
• Lay Summary
• Scientific publication
• Scientific publication

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2016
• Primary Completion (Actual): March 10, 2019
• Study Completion (Actual): March 10, 2019

Study Registration Dates

• First Submitted: July 20, 2016
• First Submitted That Met QC Criteria: August 19, 2016
• First Posted (Estimate): August 24, 2016

Study Record Updates

• Last Update Posted (Actual): March 11, 2020
• Last Update Submitted That Met QC Criteria: March 9, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; GABA Agents; GABA Antagonists; GABA-A Receptor Antagonists; S44819
• Other Study ID Numbers: CL2-44819-004; 2016-001005-16 (EudraCT Number); UTN number: U1111-1180-8991 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

They can ask all interventional clinical studies:

• submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope.

• IPD Sharing Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• IPD Sharing Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Individual Participant Data Set
2. Study Protocol
3. Statistical Analysis Plan
4. Informed Consent Form
5. Clinical Study Report
6. Study-level clinical trial data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No