NCT04734548

Brief 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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
151

participants targeted

Target at P75+ for phase_1 stroke

Timeline
Completed

Started Oct 2020

Geographic Reach
3 countries

16 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 28, 2020

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

January 28, 2021

Completed
5 days until next milestone

First Posted

Study publicly available on registry

February 2, 2021

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 25, 2022

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

September 7, 2022

Completed
Last Updated

October 21, 2022

Status Verified

October 1, 2022

Enrollment Period

1.7 years

First QC Date

January 28, 2021

Last Update Submit

October 19, 2022

Conditions

StrokeAcute StrokeIschemic Stroke

Outcome Measures

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).

    From dosing to follow-up (day 90 after dosing)

Secondary Outcomes (4)

  • Mean infarct volume

    72 hours

  • Effect in inflammatory response

    Predose and up to 72 hours post-dose

  • Early clinical course

    72 hours post-dose

  • Long-term outcome

    Day 90 post-dose

Study Arms (4)

Phase Ib ApTOLL

ACTIVE COMPARATOR

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

Phase Ib Placebo

PLACEBO COMPARATOR

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

Phase IIa ApTOLL

ACTIVE COMPARATOR

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

Drug: ApTOLL

Phase IIa Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

ApTOLLDRUG

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 ApTOLLPhase Ib ApTOLL
PlaceboOTHER

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

Phase IIa PlaceboPhase Ib Placebo

Eligibility Criteria

Age18 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥18 and ≤90 years.
  • Informed consent obtained from subject or acceptable subject surrogate (i.e. next of kin, or legal representative).
  • A new focal disabling neurologic deficit consistent with acute cerebral ischemia.
  • Baseline NIHSS obtained prior to randomization ≥ 8 points and ≤ 25 points.
  • Pre-stroke mRS score of 0 - 2.
  • 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).
  • Patients should be candidates to receive EVT treatment with or without i.v. rt-PA.
  • 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.
  • The following imaging criteria should also be met on admission neuroimaging:
  • MRI criterion: volume of DWI (Diffusion-weighted Imaging) restriction ≥5 mL and ≤70 mL OR
  • 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.
  • The subject has an indication and is planned to receive endovascular treatment of stroke according to the European Stroke Organization Guidelines.

You may not qualify if:

  • Subject has suffered a stroke in the past 1 year.
  • Occlusion (TICI 0 or TICI 1 flow) of the basilar or vertebral or posterior or anterior cerebral arteries.
  • Clinical symptoms suggestive of bilateral stroke or stroke in multiple territories.
  • Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR (international normalized ratio)\>3.0.
  • Baseline platelet count \<50,000/μL.
  • Baseline blood glucose of \<50 mg/dL or \>400 mg/dL.
  • Severe, sustained hypertension (systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg).
  • Serious, advanced, or terminal illness with anticipated life expectancy of less than 1 year.
  • Subjects with identifiable intracranial tumors.
  • History of life-threatening allergy (more than rash) to contrast medium.
  • Known renal insufficiency with creatinine ≥3 mg/dL or Glomerular Filtration Rate (GFR) \<30 mL/min.
  • Cerebral vasculitis.
  • Evidence of active systemic infection.
  • Known current use of cocaine at time of treatment.
  • Patient participating in a study involving an investigational drug or device that would impact this study.
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (16)

Centre Hospitalier Régional Universitaire de Lille

Lille, France

Location

Foundation Adolphe de Rothschild

Paris, France

Location

Centre Hospitalier Universitaire de Toulouse

Toulouse, France

Location

Universitätsklinikum Essen

Essen, Germany

Location

Hospital Universitario A Coruña

A Coruña, Spain

Location

Hospital Universitario Central de Asturias

Asturias, Spain

Location

Hospital Bellvitge

Barcelona, Spain

Location

Hospital Germans Trias i Pujol

Barcelona, Spain

Location

Hospital Universitario Vall d´Hebron

Barcelona, Spain

Location

Hospital Universitario de Gerona Dr. Josep Trueta

Girona, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario La Princesa

Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

Hospital Virgen del Rocío

Seville, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, Spain

Location

Hospital Clínico Valladolid

Valladolid, Spain

Location

Related Publications (4)

  • 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.

    PMID: 35402075BACKGROUND

  • 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.

    PMID: 37338893DERIVED

  • 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.

    PMID: 36908619DERIVED

  • 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.

    PMID: 34174279DERIVED

Related Links

MeSH Terms

Conditions

StrokeIschemic Stroke

Interventions

TLR4 antagonist ApTOLL

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Study Officials

  • Marc Ribó, MD, PhD

    aptaTargets S.L.

    STUDY DIRECTOR

  • Macarena Hernández, PhD

    aptaTargets S.L.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 28, 2021

First Posted

February 2, 2021

Study Start

October 28, 2020

Primary Completion

July 25, 2022

Study Completion

September 7, 2022

Last Updated

October 21, 2022

Record last verified: 2022-10

Data Sharing

IPD Sharing
Will not share

All results obtained in this study will be published.

Locations

FR(3)DE(1)ES(12)