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CompletedNCT04734548Updated Oct 21, 2022

Phase Ib/IIa Clinical Study of ApTOLL for the Treatment of Acute Ischemic Stroke

A Phase 1/2 interventional study of ApTOLL and Placebo in Stroke, Acute Stroke and Ischemic Stroke, sponsored by aptaTargets S.L.. Completed at 16 sites in 3 countries. Open to participants aged 18 Years to 90 Years. Per ClinicalTrials.gov, last updated 2022-10-21.

Sponsored by aptaTargets S.L. · Phase 1/2, Interventional, and Treatment

From the registry’s dates

  • Registered 3 months after the study started (first participant enrolled Oct 2020, registered Jan 2021).
Phase
Phase 1/2
Study type
Interventional
Enrollment
151
Allocation
Randomized
Ages
18 Years to 90 Years
Sex
All
01

Study summary

This is a prospective, multicenter, double-blind, randomized, placebo-controlled, Phase Ib/IIa clinical study to assess the administration of ApTOLL together with endovascular therapy in acute ischemic stroke patients who are candidates to receive reperfusion therapies.

Read the detailed description

This is a prospective, multicenter, double-blind, randomized, placebo-controlled, Phase Ib/IIa clinical study to assess the administration of ApTOLL together with endovascular therapy in acute ischemic stroke (AIS) patients with confirmed Large Vessel Occlusion (LVO) who are candidates to receive reperfusion therapies including endovascular treatment with or without i.v. rt-PA (recombinant tissue Plasminogen Activator).

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.

02

Conditions studied

  • Stroke
  • Acute Stroke
  • Ischemic Stroke
03

In context

Stroke

7,286 studies on the registry are indexed under Stroke; 2,007 are open to participants now.

This study's enrollment of 151 is above the median of 50 across 5,369 interventional studies indexed under Stroke.

Browse Stroke studies →

Lead sponsor

aptaTargets S.L. is the lead sponsor of 3 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 90 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Age ≥18 and ≤90 years.
  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

Exclusion Criteria:

  1. Subject has suffered a stroke in the past 1 year.
  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.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Sequential assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
151 participants (actual)

Study arms

  • Active comparator
    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.

    Drug: ApTOLL

  • Placebo comparator
    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.

    Other: Placebo

  • Active comparator
    Phase IIa ApTOLL

    ApTOLL is administered intravenously (two doses selected in Phase Ib). The two dose levels include 35 patients each one.

    Drug: ApTOLL

  • Placebo comparator
    Phase IIa Placebo

    Placebo is administered intravenously in one arm which includes 49 patients.

    Other: Placebo

Interventions

  • DrugApTOLL

    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.

  • OtherPlacebo

    White freeze-dried powder which is indistinguishable to ApTOLL for taste, color, texture and size.

06

What researchers measure

Primary outcomes

  1. Safety of ApTOLL

    To assess if ApTOLL is safe when combined with EVT therapy as determined by: 1. Death. 2. Adverse events that occur during the study. 3. Physical examination. 4. Laboratory tests. 5. Recurrent stroke. 6. Symptomatic intracranial hemorrhage (sICH).

    Time frame: From dosing to follow-up (day 90 after dosing)

Secondary outcomes

  1. Mean infarct volume

    Magnetic Resonance Image

    Time frame: 72 hours

  2. Effect in inflammatory response

    Proinflammatory markers in blood between study groups

    Time frame: Predose and up to 72 hours post-dose

  3. Early clinical course

    NIHSS (National institute of Health Stroke Scale). The maximum possible score is 42, with the minimum score being a 0 (the higher the score, the more impaired a stroke patient is)

    Time frame: 72 hours post-dose

  4. Long-term outcome

    mRS (modified Ranking Score). Coded from 0 (no symptoms at all) through 5 (severe disability) 6 (death).

    Time frame: Day 90 post-dose

07

Study locations

16 sites
  • 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 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 A Coruña
    Coruña, Spain
  • Hospital Universitario de Gerona Dr. Josep Trueta
    Gerona, 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
    Sevilla, Spain
  • Hospital Universitario y Politécnico La Fe
    Valencia, Spain
  • Hospital Clínico Valladolid
    Valladolid, Spain
08

References and documents

Publications

  • 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. PubMed 35402075 ↗
  • 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. PubMed 34174279 ↗

Individual participant data

Plan to share: No — All results obtained in this study will be published.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 21, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04734548
Lead sponsor
aptaTargets S.L.
Collaborators
Ministry of Science and Innovation, Spain, Anagram
Responsible party
Sponsor
First posted
Feb 2, 2021
Start date
Oct 28, 2020
Primary completion
Jul 25, 2022
Completion
Sep 7, 2022
Last update
Oct 21, 2022

Study contacts

Marc Ribó, MD, PhD
study director · aptaTargets S.L.
Macarena Hernández, PhD
study director · aptaTargets S.L.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Oct 2022. You cannot join it, but the record below documents what was studied.

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