According to the results of the APRIL study, in which the Bellvitge University Hospital (HUB) and IDIBELL have participated, ApTOLL has shown good safety in 151 patients with acute ischaemic stroke. The study also highlights that preliminary efficacy results show that the drug significantly reduces mortality and long-term functional disability.
The prestigious scientific journal JAMA Neurology has published the positive results of the aptaTargets Phase 1b/2a APRIL clinical trial, which evaluated the safety and efficacy of the innovative neuroprotective drug ApTOLL in combination with endovascular treatment (EVT) in patients with acute ischaemic stroke.
Study results have shown that administration of 0.2 mg/kg ApTOLL within 6 hours after acute ischaemic stroke in combination with VTE was safe and well tolerated and was also associated with a reduction in mortality from 18% to 5% along with a reduction in functional disability at 90 days versus placebo.
Dr Pere Cardona, director of the Neurovascular Program and the Stroke Unit of the Neurology Service of the HUB and principal investigator of IDIBELL, stressed the relevance of the trial results, since “it is the first neuroprotective drug that shows great efficacy and safety in the hyperacute phase of severe stroke and this makes it a candidate for imminent hospital and pre-hospital studies, in which the HUB and IDIBELL are co-leaders”.
APRIL is a Phase 1b/2a, double-blind, randomised, multicentre, placebo-controlled, double-blind, placebo-controlled clinical trial conducted at 14 leading stroke centres in Spain and France, which started in 2020. In total, the study has included 151 patients: 32 in Phase 1b and 119 in Phase 2a. The study population was men and non-pregnant women aged 18/90 years with a disabling stroke at the time of randomisation.
Patients randomly received intravenous ApTOLL or placebo prior to thrombectomy. The total population analysed was 139 patients, of which 42 patients received 0.05 mg/kg ApTOLL, 42 patients received 0.02 mg/kg ApTOLL and 55 patients received placebo.
The primary endpoint has been safety as determined by death, symptomatic intracranial haemorrhage, malignant stroke and recurrent stroke. Secondary efficacy-related endpoints included mean final infarct volume measured at 72 hours, stroke symptom severity assessed by the US National Institutes of Health (NIH) Stroke Scale at 72 hours, and 90-day disability in terms of the modified Rankin Score (mRS). Stroke affects 1 in 4 adults over the age of 25 in their lifetime. This makes stroke the second leading cause of death and a leading cause of long-term disability.
Acute ischaemic stroke accounts for 85% of the total. Although reperfusion therapies have been shown in recent years to consistently achieve arterial recanalisation in 85-90% of cases, more than 50% of treated patients develop moderate to severe disability. In this context, there is a clear medical need to develop new neuroprotective drugs to improve stroke outcomes in parallel to reperfusion therapies.
Safety and Efficacy of ApTOLL in Patients with Ischemic Stroke Undergoing Endovascular Treatment
Hernández-Jiménez M, Abad-Santos F, Cotgreave I, Gallego J, Jilma B, Flores A, Govin T, Vivancos J, Hernández-Pérez M, Molina C, Montaner J, Casariego J, Dalsgaard M, Liebeskind D, Cobo E, Castellanos M, Cardona Portela P, Masjuán J, Moniche F, Tembl J, Terceño Izaga M, Arenillas J, Callejas P, Olivot J, Calviere L, Henon H, Mazighi M, Piñeiro D, Pugliese M, González V, Moro M, Garcia-Tornel A, Lizasoain I, Ribó M. JAMA Neurology, 2023.