The MaTRISS 2 study is a phase 2 randomized, double-blinded and placebo-controlled trial aimed at recruiting 60 subjects (30 placebo and 30 active) from 15 stroke centers in France. The main objective will be to assess the efficacy of OTR4132-MD in patients with anterior ischemic stroke after endovascular thrombectomy. One dose will be tested (2 mg) against placebo. The main outcomes will be NIHSS (neurological score) at 24 hours, rate of intracranial hemorrhages at 24 hours, MRI lesion volume at 3 months and neurological scores at 3 months.
* The aim of the study is to confirm previous safety and encouraging efficacy data obtained from the MATRISS first-in man study and animal studies. . This is a prospective double-blinded placebo-controlled trial. The trial will recruit 60 subjects (30 per group) with anterior circulation acute ischemic stroke (AIS) re-vascularized (TICI score 2b - 3) by endovascular thrombectomy. Subjects will be followed for 3 months after a single administration of OTR4132-MD or placebo. * The study is double blinded and there is no way to distinguish the active product from the placebo. Neither the treating nor evaluating physicians, nor the patients, will be informed of the allocation of the treatment before database lock and the end of the trial. * The use of a placebo is justified by the absence of any neuroprotector approved in France in this indication so there is no comparator. The administration of OTR4132-MD or Placebo will be done in addition to the best standard of care and does not result in any additional po-tentially harmful procedure. * The study will include 60 patients (30 in the active group and 30 in the placebo group) which is considered sufficient to demonstrate superiority of treatment over placebo with a 5% risk two-sided level (see sample size calculation). * The study will evaluate a single dose of OTR4132-MD (2 mg) over Placebo. This dose has been selected as the highest and safest dose tested in the previous MATRISS dose-escalation study. * A 3 months-follow-up period is estimated sufficient to evaluate the residual disability and is recommended in the guideline "Points to consider on clinical investigation of medicinal products for the treatment of acute stroke" (EMA, 2001, CPMP/EWP/560/98). * A Data Safety Monitoring Board (DSMB) will be set up. It will consist of three medical experts in neurology and stroke trials. Other relevant expertise will be consulted if deemed neces-sary. The members of the committee will review interim blinded safety and efficacy study da-ta. Unblinding procedures will be set up in individual cases if deemed necessary.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
60
OTR4132 is a new ReGeneraTing Agent (RGTA®) which is a polymer of glucose (α-1,6 bounds, i.e. dextran backbone) engineered to mimic heparan sulphate (HS) in all three mechanical functions (extracellular matrix scaffold element, protector of matrix pro-teins and cellular communication peptides storage sites) but differ from HS by their resistance to glycanases. OTR4132 allows a restoration of the matrix architecture which secondarily facilitates cell survival and recovery at the site of injury.
saline solution
Centre Hospitalier Universi-taire de Bordeaux-Hôpital Pellegrin
Bordeaux, France
Centre hospitalier universi-taire de Brest (Cavale Blanche)
Brest, France
CHU Henri-Mondor
Créteil, France
Centre Hospitalier Universitaire de Martinique
Fort de France, France
Centre Hospitalier Universitaire Grenoble Alpes
Grenoble, France
Centre Hospitalier Régional Universitaire de Lille- Hôpital Roger Salengro
Lille, France
Hôpitaux Universitaires De Marseille Timone-AP-HM
Marseille, France
Centre Hospitalier Régional Universitaire de Nancy
Nancy, France
UIC Imagerie et Neurovasculaire CHU de Nantes
Nantes, France
Hôpital de la Pitié Salpêtrière - AP-HP
Paris, France
...and 5 more locations
Baseline-Adjusted 24-Hour NIHSS
The NIH Stroke Scale (NIHSS) is based on the collection of 15 clinical neurological items. It allows for an accurate and rapid assessment of observed deficits. A large number of publications have shown that the NIHSS score at 24 hours is the best prognostic factor for long-term functional disability and is closely correlated with disability scores at 3 months. An NIHSS score between 1 and 4 means a minor stroke, between 5 and 15, a moderate stroke, above 15 points, a severe stroke. The maximum score is 42
Time frame: 24 hours
Change in modified Rankin scale (mRS) at 3 months
The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire. The Modified Rankin Score (mRS) is the most widely used outcome measure in stroke clinical trials. Standardized interviews to obtain a mRS score are recommended at 3 months (90 days) following hospital discharge. The mRS will be used as a continuous endpoint (change in mRS at 3 months and in a responder analysis (mRS 0-2 at 3 months).
Time frame: 3 months
Changes in total lesion volume from baseline to 3 months (MRI)
Follow-up infarct volume is a more direct measure of biological effect of treatment. Infarct volume is less likely to be confounded by intervening comorbid illness, rehabilitation therapy, or non-stroke related pathology. volumetric analyses will be analyzed by an independent core laboratory
Time frame: 3 months
The rate of Intracranial hemorrhage at 24-hour
The rate of Intracranial hemorrhage at 24-hour based on Heidelberg classification is considered an important endpoint to assess the potential performance of OTR4132-MD in the repair of the blood brain barrier
Time frame: 24 hours
Barthel Index at 3-months
Modified Barthel Index (from 0 to 20) is a measure of physical disability used widely to assess behaviour relating to activities of daily living. It measures what patients do in practice. Assessment is made by anyone who knows the patient well. 100: normal \<99 represents slight dependency \<90 represents moderate disability \<60 represents severe disability \>20 represents total dependency
Time frame: 3 months
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