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

October 19, 2022 updated by: aptaTargets S.L.

A Double-Blind, Placebo-Controlled, Randomized, Phase Ib/IIa Clinical Study of ApTOLL for the Treatment of Acute Ischemic Stroke

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
151

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lille, France
        • Centre Hospitalier Régional Universitaire de Lille
      • Paris, France
        • Foundation Adolphe de Rothschild
      • Toulouse, France
        • Centre Hospitalier Universitaire de Toulouse
  • Germany
      • Essen, Germany
        • Universitätsklinikum Essen
  • Spain
      • Asturias, Spain
        • Hospital Universitario Central de Asturias
      • Barcelona, Spain
        • Hospital Universitario Vall d´Hebron
      • Barcelona, Spain
        • Hospital Germans Trias i Pujol
      • Barcelona, Spain
        • Hospital Bellvitge
      • Coruña, Spain
        • Hospital Universitario A Coruña
      • Gerona, Spain
        • Hospital Universitario de Gerona Dr. Josep Trueta
      • Madrid, Spain
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain
        • Hospital Universitario Ramón y Cajal
      • Madrid, Spain
        • Hospital Universitario La Princesa
      • Sevilla, Spain
        • Hospital Virgen Del Rocio
      • Valencia, Spain
        • Hospital Universitario y Politécnico La Fe
      • Valladolid, Spain
        • Hospital Clínico Valladolid

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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:

  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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
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 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
White freeze-dried powder which is indistinguishable to ApTOLL for taste, color, texture and size.
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
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 Comparator: Phase IIa Placebo
Placebo is administered intravenously in one arm which includes 49 patients.
Other: Placebo
White freeze-dried powder which is indistinguishable to ApTOLL for taste, color, texture and size.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety of ApTOLL
Time Frame: From dosing to follow-up (day 90 after dosing)

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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean infarct volume
Time Frame: 72 hours
Magnetic Resonance Image
72 hours
Effect in inflammatory response
Time Frame: Predose and up to 72 hours post-dose
Proinflammatory markers in blood between study groups
Predose and up to 72 hours post-dose
Early clinical course
Time Frame: 72 hours post-dose
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)
72 hours post-dose
Long-term outcome
Time Frame: Day 90 post-dose
mRS (modified Ranking Score). Coded from 0 (no symptoms at all) through 5 (severe disability) 6 (death).
Day 90 post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
aptaTargets S.L.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Science and Innovation Spanish Ministry
Anagram

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Macarena Hernández, PhD, aptaTargets S.L.
  • Study Director: Marc Ribó, MD, PhD, aptaTargets S.L.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 28, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 25, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 7, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 28, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 28, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 2, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 21, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 19, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • APRIL

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

All results obtained in this study will be published.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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