Phase Ib/IIa Clinical Study of ApTOLL for the Treatment of Acute Ischemic Stroke
NCT ID: NCT04734548
Last Updated: 2022-10-21
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1/PHASE2
151 participants
INTERVENTIONAL
2020-10-28
2022-09-07
Brief Summary
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Detailed Description
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The study will be a Phase Ib/IIa trial where 2 doses selected, based on safety criteria, on Phase Ib will be administered in the following Phase IIa.The objective of the study is to evaluate if administration of ApTOLL at different doses is safe and well tolerated compared to placebo when administered with endovascular therapy (EVT), with or without i.v. rt-PA, in the AIS target population.
Conditions
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Study Design
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RANDOMIZED
SEQUENTIAL
TREATMENT
QUADRUPLE
Study Groups
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Phase Ib ApTOLL
ApTOLL is administered intravenously in a single ascending dose pattern in four dose levels (0.025mg/kg - 0.2mg/kg). All levels include six patients.
ApTOLL
ApTOLL is a Toll-like receptor 4 (TLR4) antagonist, a receptor that is involved in innate immune responses but also responds to tissue damage, and therefore it is directly involved in a large number of diseases where the inflammatory response is involved. ApTOLL has demonstrated specific binding to human TLR4 as well as a TLR4 antagonistic effect, reducing inflammation and improving outcome after different disease models.
Phase Ib Placebo
Placebo is administered intravenously in a single ascending dose pattern in four dose levels (0.025mg/kg - 0.2mg/kg). All levels include two patients.
Placebo
White freeze-dried powder which is indistinguishable to ApTOLL for taste, color, texture and size.
Phase IIa ApTOLL
ApTOLL is administered intravenously (two doses selected in Phase Ib). The two dose levels include 35 patients each one.
ApTOLL
ApTOLL is a Toll-like receptor 4 (TLR4) antagonist, a receptor that is involved in innate immune responses but also responds to tissue damage, and therefore it is directly involved in a large number of diseases where the inflammatory response is involved. ApTOLL has demonstrated specific binding to human TLR4 as well as a TLR4 antagonistic effect, reducing inflammation and improving outcome after different disease models.
Phase IIa Placebo
Placebo is administered intravenously in one arm which includes 49 patients.
Placebo
White freeze-dried powder which is indistinguishable to ApTOLL for taste, color, texture and size.
Interventions
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ApTOLL
ApTOLL is a Toll-like receptor 4 (TLR4) antagonist, a receptor that is involved in innate immune responses but also responds to tissue damage, and therefore it is directly involved in a large number of diseases where the inflammatory response is involved. ApTOLL has demonstrated specific binding to human TLR4 as well as a TLR4 antagonistic effect, reducing inflammation and improving outcome after different disease models.
Placebo
White freeze-dried powder which is indistinguishable to ApTOLL for taste, color, texture and size.
Eligibility Criteria
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Inclusion Criteria
2. Informed consent obtained from subject or acceptable subject surrogate (i.e. next of kin, or legal representative).
3. A new focal disabling neurologic deficit consistent with acute cerebral ischemia.
4. Baseline NIHSS obtained prior to randomization ≥ 8 points and ≤ 25 points.
5. Pre-stroke mRS score of 0 - 2.
6. Treatable as soon as possible and at least within 6 hours of symptom onset, defined as point in time when the subject was last seen well (at baseline).
7. Patients should be candidates to receive EVT treatment with or without i.v. rt-PA.
8. Occlusion (TICI 0 or TICI 1 flow), of the terminal internal carotid artery (TICA), M1 or M2 segments of the middle cerebral artery, suitable for mechanical embolectomy, confirmed on Computed Tomography Angiography.
9. The following imaging criteria should also be met on admission neuroimaging:
1. MRI criterion: volume of DWI (Diffusion-weighted Imaging) restriction ≥5 mL and ≤70 mL OR
2. CT criterion: Alberta Stroke program early CT score (ASPECTS) 6 to 10 on baseline CT AND infarct core determined on admission CTPerfusion by Cerebral Blood Flow\<30%: ≥5 mL and ≤70 mL.
10. The subject has an indication and is planned to receive endovascular treatment of stroke according to the European Stroke Organization Guidelines.
Exclusion Criteria
2. Occlusion (TICI 0 or TICI 1 flow) of the basilar or vertebral or posterior or anterior cerebral arteries.
3. Clinical symptoms suggestive of bilateral stroke or stroke in multiple territories.
4. Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR (international normalized ratio)\>3.0.
5. Baseline platelet count \<50,000/μL.
6. Baseline blood glucose of \<50 mg/dL or \>400 mg/dL.
7. Severe, sustained hypertension (systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg).
8. Serious, advanced, or terminal illness with anticipated life expectancy of less than 1 year.
9. Subjects with identifiable intracranial tumors.
10. History of life-threatening allergy (more than rash) to contrast medium.
11. Known renal insufficiency with creatinine ≥3 mg/dL or Glomerular Filtration Rate (GFR) \<30 mL/min.
12. Cerebral vasculitis.
13. Evidence of active systemic infection.
14. Known current use of cocaine at time of treatment.
15. Patient participating in a study involving an investigational drug or device that would impact this study.
16. Patients that are unlikely to be available for a 90-day follow-up (e.g. no fixed home address, visitor from overseas).
17. Female who is pregnant or lactating or has a positive pregnancy test at time of admission.
18. CT or MRI evidence of hemorrhage (the presence of microbleeds is allowed).
19. Significant mass effect with midline shift.
20. Suspicion of aortic dissection presumed septic embolus, or suspicion of bacterial endocarditis.
18 Years
90 Years
ALL
No
Sponsors
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Ministry of Science and Innovation, Spain
OTHER_GOV
Anagram
UNKNOWN
aptaTargets S.L.
INDUSTRY
Responsible Party
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Principal Investigators
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Marc Ribó, MD, PhD
Role: STUDY_DIRECTOR
aptaTargets S.L.
Macarena Hernández, PhD
Role: STUDY_DIRECTOR
aptaTargets S.L.
Locations
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Centre Hospitalier Régional Universitaire de Lille
Lille, , France
Foundation Adolphe de Rothschild
Paris, , France
Centre Hospitalier Universitaire de Toulouse
Toulouse, , France
Universitätsklinikum Essen
Essen, , Germany
Hospital Universitario A Coruña
A Coruña, , Spain
Hospital Universitario Central de Asturias
Asturias, , Spain
Hospital Bellvitge
Barcelona, , Spain
Hospital Germans Trias i Pujol
Barcelona, , Spain
Hospital Universitario Vall d´Hebron
Barcelona, , Spain
Hospital Universitario de Gerona Dr. Josep Trueta
Girona, , Spain
Hospital Universitario 12 de Octubre
Madrid, , Spain
Hospital Universitario La Princesa
Madrid, , Spain
Hospital Universitario Ramón y Cajal
Madrid, , Spain
Hospital Virgen del Rocío
Seville, , Spain
Hospital Universitario y Politécnico La Fe
Valencia, , Spain
Hospital Clínico Valladolid
Valladolid, , Spain
Countries
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References
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Hernandez-Jimenez M, Martin-Vilchez S, Ochoa D, Mejia-Abril G, Roman M, Camargo-Mamani P, Luquero-Bueno S, Jilma B, Moro MA, Fernandez G, Pineiro D, Ribo M, Gonzalez VM, Lizasoain I, Abad-Santos F. First-in-human phase I clinical trial of a TLR4-binding DNA aptamer, ApTOLL: Safety and pharmacokinetics in healthy volunteers. Mol Ther Nucleic Acids. 2022 Mar 9;28:124-135. doi: 10.1016/j.omtn.2022.03.005. eCollection 2022 Jun 14.
Hernandez-Jimenez M, Abad-Santos F, Cotgreave I, Gallego J, Jilma B, Flores A, Jovin TG, Vivancos J, Hernandez-Perez M, Molina CA, Montaner J, Casariego J, Dalsgaard M, Liebeskind DS, Cobo E, Castellanos M, Portela PC, Masjuan J, Moniche F, Tembl JI, Terceno Izaga M, Arenillas JF, Callejas P, Olivot JM, Calviere L, Henon H, Mazighi M, Pineiro D, Pugliese M, Gonzalez VM, Moro MA, Garcia-Tornel A, Lizasoain I, Ribo M. Safety and Efficacy of ApTOLL in Patients With Ischemic Stroke Undergoing Endovascular Treatment: A Phase 1/2 Randomized Clinical Trial. JAMA Neurol. 2023 Aug 1;80(8):779-788. doi: 10.1001/jamaneurol.2023.1660.
Hernandez-Jimenez M, Abad-Santos F, Cotgreave I, Gallego J, Jilma B, Flores A, Jovin TG, Vivancos J, Molina CA, Montaner J, Casariego J, Dalsgaard M, Hernandez-Perez M, Liebeskind DS, Cobo E, Ribo M. APRIL: A double-blind, placebo-controlled, randomized, Phase Ib/IIa clinical study of ApTOLL for the treatment of acute ischemic stroke. Front Neurol. 2023 Feb 24;14:1127585. doi: 10.3389/fneur.2023.1127585. eCollection 2023.
Duran-Laforet V, Pena-Martinez C, Garcia-Culebras A, Alzamora L, Moro MA, Lizasoain I. Pathophysiological and pharmacological relevance of TLR4 in peripheral immune cells after stroke. Pharmacol Ther. 2021 Dec;228:107933. doi: 10.1016/j.pharmthera.2021.107933. Epub 2021 Jun 24.
Related Links
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Biotechnology company specialized in therapeutic aptamers
Other Identifiers
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APRIL
Identifier Type: -
Identifier Source: org_study_id
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