APRIL: A double-blind, placebo-controlled, randomized, Phase Ib/IIa clinical study of ApTOLL for the treatment of acute ischemic stroke

被引：20

作者：

Hernandez-Jimenez, Macarena ^{[1
]}

Abad-Santos, Francisco ^{[2
,3
]}

Cotgreave, Ian ^{[4
]}

Gallego, Jaime ^{[5
]}

Jilma, Bernd ^{[6
]}

Flores, Alan ^{[7
]}

Jovin, Tudor G. ^{[8
]}

Vivancos, Jose ^{[9
]}

Molina, Carlos A. ^{[10
]}

Montaner, Joan ^{[11
]}

Casariego, Joaquin ^{[12
]}

Dalsgaard, Mads ^{[13
]}

Hernandez-Perez, Maria ^{[14
]}

Liebeskind, David S. ^{[15
]}

Cobo, Erik ^{[16
]}

Ribo, Marc ^{[1
,10
]}

机构：

[1] AptaTargets SL, Madrid, Spain

[2] Univ Autonoma Madrid UAM, Hosp Univ La Princesa, Clin Pharmacol Dept, Inst Invest Sanitaria La Princesa IP, Madrid, Spain

[3] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

[4] Res Inst Sweden, Dept Chem & Pharmaceut Safety, Div Bioecon & Hlth, Sodertalje, Sweden

[5] Neurol Ctr Navarra, Navarra, Spain

[6] Med Univ Vienna, Dept Clin Pharmacol, Vienna, Austria

[7] Hosp Joan 23, Stroke Unit, Tarragona, Spain

[8] Cooper Neurol Inst, Camden, AR USA

[9] Hosp La Princesa, Dept Neurol, Stroke Unit, Madrid, Spain

[10] Hosp Valle De Hebron, Dept Neurol, Stroke Unit, Barcelona, Spain

[11] Hosp Macarena, Dept Neurol, Seville, Spain

[12] Aldebaran Hlth Intelligence SL, Madrid, Spain

[13] Cureteq AG, Zug, Switzerland

[14] Hosp Badalona Germans Trias & Pujol, Dept Neurol, Stroke Unit, Barcelona, Spain

[15] UCLA, Dept Neurol, Neurovasc Imaging Res Core, Stroke Ctr, Los Angeles, CA USA

[16] Barcelona Tech UPC, Stat & Operat Res, Barcelona, Spain

来源：

FRONTIERS IN NEUROLOGY | 2023年 / 14卷

关键词：

clinical trial; stroke; aptamer; inflammation; neuroprotection; ApTOLL; TLR4; ENDOVASCULAR TREATMENT; NEUROPROTECTION; THROMBECTOMY; SAFETY;

D O I：

10.3389/fneur.2023.1127585

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

In the reperfusion era, a new paradigm of treating patients with endovascular treatment (EVT) and neuroprotective drugs is emerging as a promising therapeutic option for patients with acute ischemic stroke (AIS). In this context, ApTOLL, a Toll-like receptor 4 (TLR4) antagonist with proven neuroprotective effect in preclinical models of stroke and a very good pharmacokinetic and safety profile in healthy volunteers, is a promising first-in-class aptamer with the potential to address this huge unmet need. This protocol establishes the clinical trial procedures to conduct a Phase Ib/IIa clinical study (APRIL) to assess ApTOLL tolerability, safety, pharmacokinetics, and biological effect in patients with AIS who are eligible for EVT. This will be a multicenter, double-blind, randomized, placebo-controlled, Phase Ib/IIa clinical study to evaluate the administration of ApTOLL together with EVT in patients with AIS. The study population will be composed of men and non-pregnant women with confirmed AIS with a < 6h window from symptoms onset to ApTOLL/placebo administration. The trial is currently being conducted and is divided into two parts: Phase Ib and Phase IIa. In Phase Ib, 32 patients will be allocated to four dose ascending levels to select, based on safety criteria, the best two doses to be administered in the following Phase IIa in which 119 patients will be randomized to three arms of treatment (dose A, dose B, and placebo).

引用

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