First in Human Clinical Trial of ApTOLL in Healthy Volunteers

March 16, 2022 updated by: aptaTargets S.L.

First in Human Dose Ascending, Randomized, Placebo-Controlled Clinical Trial to Assess Tolerability and Pharmacokinetics of ApTOLL in Healthy Volunteers

This is a Phase I, first-in-human, dose ascending, randomized, placebo-controlled clinical study to assess the tolerability and pharmacokinetics of ApTOLL in healthy volunteers. ApTOLL is an aptamer able to antagonize TLR4 receptor and, therefore, to reduce the inflammatory response.

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 Phase I clinical trial is divided in two parts: the first part (part A) is a single dose escalation study and the second (part B) is a multiple dose study. Both are performed in healthy volunteers.

  • First part: a single dose, i.v. administration (slow infusion), dose escalation with a maximum of 7 single dose levels, randomized, double-blind, placebo-controlled (saline solution), in healthy subjects.
  • Second part: a multiple dose, i.v. administration (slow infusion), randomized, double-blind, placebo-controlled (saline solution), in healthy subjects.

The main objectives of this study are:

  1. To evaluate the tolerability and pharmacokinetic characteristics of ApTOLL in healthy volunteers, after single dose administration in fasting conditions, following an ascending dosing scheme.
  2. To evaluate the tolerability and pharmacokinetic characteristics of ApTOLL in healthy volunteers, after multiple dose administration in fasting conditions.

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.
46

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 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

  • Spain
      • Madrid, Spain, 28006
        • Clinical Pharmacology Department. Hospital Universitario de La Princesa

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

14 years to 51 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female subjects (women without possibility of becoming pregnant) willing and able to give their written consent to participate in the trial.
  2. Healthy subjects aged within: 18 to 55 years (limits included).
  3. Clinical history and physical examination results within normality.
  4. Vital signs and electrocardiogram without clinically significant pathologic abnormalities and with QTc (Corrected QT space) values lower than 450 ms.
  5. Body weight between 65 and 85 kg, inclusive.
  6. BMI (Body Mass Index) between 19.0 and 30.0 kg/m2.
  7. No clinically significant abnormalities in haematology, biochemistry, serology (Ag HBV (Hepatitis B Virus), HCV (Hepatitis C Virus) antibodies, HIV (Human Immunodeficiency Virus) antibodies) and urine tests.

Exclusion Criteria:

  1. Any chronic medical condition (such as type 1 diabetes) requiring chronic treatment.
  2. Evidence of active infection requiring antibiotic therapy within 14 days prior to screening.
  3. Medical history of vasculitis or any autoimmune disease excluding seasonal allergic rhinitis and childhood history of atopic dermatitis.
  4. Subject having at screening examination a sitting blood pressure more than or equal to 140/90 mm Hg or lower than or equal to 90/50 mmHg.
  5. Subject having at screening examination a pulse more than 100 beats per minute or a body temperature more than 37.7 °C. or a respiratory rate outside the normal range of (14-20 breath per minute).
  6. History of any treatment for cancer within the past 2 years, other than basal cell or squamous cell carcinoma of the skin.
  7. Clinically significant abnormalities in screening laboratory tests.
  8. Any prescription, over-the-counter and herbal medications within 10 days prior to study dosing.
  9. Use of an investigational drug within 3 months prior to dosing in this study.
  10. Psychiatric history of current or past psychosis, bipolar disorder, clinical depression, or anxiety disorder requiring chronic medication within the past 5 years.
  11. Pregnant or breastfeeding women.
  12. History of substance abuse, including alcohol.
  13. Smokers.
  14. History of substance or drug dependence, or positive urine drug screen at screening visit.
  15. History of head injury.
  16. History of sensitivity to any drug.
  17. Having donated blood in the last month before start of the study.
  18. Any reason or opinion of the investigator that would prevent the subject from participation in the study.
  19. Inability to follow the instructions or an unwillingness to collaborate during the study.

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: Triple

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: ApTOLL single dose
ApTOLL is administered intravenously in a single ascending dose pattern in seven dose levels (0.7mg - 70mg). Levels 1 - 3 include one subject per level and levels 4 - 7 include six subjects per level (1 sentinel + 5 subjects).
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 inflammatoryy 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: Placebo single dose
Placebo is administered intravenously during seven dose levels. Levels 1 - 3 include one subject per level and levels 4 - 7 include two subjects per level (1 sentinel + 1 subject).
Other: Placebo
100 mL 0.9% Sodium Chloride solution
Active Comparator: ApTOLL multiple dose
ApTOLL is administered intravenously every eight hours during 24h (21mg). This arm includes six subjects (1 sentinel + 5 subjects).
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 inflammatoryy 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: Placebo multiple dose
Placebo is administered intravenously every eight hours during 24h. This arm includes twosubjects (1 sentinel + 1 subject).
Other: Placebo
100 mL 0.9% Sodium Chloride solution

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
Incidence of Adverse Events as assessed by CTCAE v4.0
Time Frame: From dosing to follow-up (day 15 after dosing)
Adverse Events that occur during the study
From dosing to follow-up (day 15 after dosing)
Peak Plasma Concentration
Time Frame: Predose and at different times up to 72 hours post-dose
Peak Plasma Concentration (Cmax)
Predose and at different times up to 72 hours post-dose
Area under the plasma concentration
Time Frame: Predose and at different times up to 72 hours post-dose
Area under the plasma concentration versus time curve (AUC)
Predose and at different times up to 72 hours post-dose

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
Vital signs
Time Frame: From screening to follow-up (day 15 after dosing)
Heart Rate
From screening to follow-up (day 15 after dosing)
Vital signs
Time Frame: From screening to follow-up (day 15 after dosing)
Blood Presure
From screening to follow-up (day 15 after dosing)
Vital signs
Time Frame: From screening to follow-up (day 15 after dosing)
Respiratory Rate
From screening to follow-up (day 15 after dosing)
Vital signs
Time Frame: From screening to follow-up (day 15 after dosing)
Body Temperature
From screening to follow-up (day 15 after dosing)
Laboratory determinations
Time Frame: From screening to follow-up (day 15 after dosing)
Number of patients with treatment-related alterations coagulation parameters (Protrombine Time (PT) and activated Partial Tromboplastine Time (aPTT))
From screening to follow-up (day 15 after dosing)
Laboratory determinations
Time Frame: From screening to follow-up (day 15 after dosing)
Number of patients with treatment-related alterations Complement Factors activation determined in blood
From screening to follow-up (day 15 after dosing)

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.
  • Principal Investigator: Dolores Ochoa, MD, PhD, Clinical Trials Unit. Hospital Universitario La Princesa

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.
July 18, 2019

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.
February 27, 2020

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.
March 20, 2020

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 26, 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.
February 4, 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 5, 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.
March 17, 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.
March 16, 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.
January 1, 2021

More Information

Terms related to this study

Keywords

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.
  • ApTOLL-FIH-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

All the data from this study are going to 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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