First in Human Clinical Trial of ApTOLL in Healthy Volunteers

NCT04742062 | Completed Phase 1 DMC

• 1 other identifier: ApTOLL-FIH-01
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Stroke

Keywords

Healthy volunteers; ApTOLL

Outcome Measures

Primary Outcomes (3)

• Incidence of Adverse Events as assessed by CTCAE v4.0

  Adverse Events that occur during the study

  From dosing to follow-up (day 15 after dosing)

• Peak Plasma Concentration

  Peak Plasma Concentration (Cmax)

  Predose and at different times up to 72 hours post-dose

• Area under the plasma concentration

  Area under the plasma concentration versus time curve (AUC)

  Predose and at different times up to 72 hours post-dose

Secondary Outcomes (6)

• Vital signs

  From screening to follow-up (day 15 after dosing)

• Vital signs

  From screening to follow-up (day 15 after dosing)

• Vital signs

  From screening to follow-up (day 15 after dosing)

• Vital signs

  From screening to follow-up (day 15 after dosing)

• Laboratory determinations

  From screening to follow-up (day 15 after dosing)

Study Arms (4)

ApTOLL single dose

ACTIVE COMPARATOR

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

Placebo single dose

PLACEBO COMPARATOR

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

ApTOLL multiple dose

ACTIVE COMPARATOR

ApTOLL is administered intravenously every eight hours during 24h (21mg). This arm includes six subjects (1 sentinel + 5 subjects).

Drug: ApTOLL

Placebo multiple dose

PLACEBO COMPARATOR

Placebo is administered intravenously every eight hours during 24h. This arm includes twosubjects (1 sentinel + 1 subject).

Other: Placebo

Interventions

ApTOLL DRUG

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.

ApTOLL multiple dose; ApTOLL single dose

Placebo OTHER

100 mL 0.9% Sodium Chloride solution

Placebo multiple dose; Placebo single dose

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female subjects (women without possibility of becoming pregnant) willing and able to give their written consent to participate in the trial.
• Healthy subjects aged within: 18 to 55 years (limits included).
• Clinical history and physical examination results within normality.
• Vital signs and electrocardiogram without clinically significant pathologic abnormalities and with QTc (Corrected QT space) values lower than 450 ms.
• Body weight between 65 and 85 kg, inclusive.
• BMI (Body Mass Index) between 19.0 and 30.0 kg/m2.
• 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.

You may not qualify if:

• Any chronic medical condition (such as type 1 diabetes) requiring chronic treatment.
• Evidence of active infection requiring antibiotic therapy within 14 days prior to screening.
• Medical history of vasculitis or any autoimmune disease excluding seasonal allergic rhinitis and childhood history of atopic dermatitis.
• 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.
• 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).
• History of any treatment for cancer within the past 2 years, other than basal cell or squamous cell carcinoma of the skin.
• Clinically significant abnormalities in screening laboratory tests.
• Any prescription, over-the-counter and herbal medications within 10 days prior to study dosing.
• Use of an investigational drug within 3 months prior to dosing in this study.
• Psychiatric history of current or past psychosis, bipolar disorder, clinical depression, or anxiety disorder requiring chronic medication within the past 5 years.
• Pregnant or breastfeeding women.
• History of substance abuse, including alcohol.
• Smokers.
• History of substance or drug dependence, or positive urine drug screen at screening visit.
• History of head injury.

Sponsors & Collaborators

• aptaTargets S.L.: lead
• Ministry of Science and Innovation, Spain: collaborator
• Anagram: collaborator

Study Sites (1)

Clinical Pharmacology Department. Hospital Universitario de La Princesa

Madrid, 28006, Spain

Location

Related Publications (1)

• 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: 34174279 DERIVED

Related Links

• Biotechnology company specialized in therapeutic aptamers

MeSH Terms

Conditions

Stroke

Interventions

TLR4 antagonist ApTOLL

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Dolores Ochoa, MD, PhD

  Clinical Trials Unit. Hospital Universitario La Princesa

  PRINCIPAL INVESTIGATOR

• Macarena Hernández, PhD

  aptaTargets S.L.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: January 26, 2021
• First Posted: February 5, 2021
• Study Start: July 18, 2019
• Primary Completion: February 27, 2020
• Study Completion: March 20, 2020
• Last Updated: March 17, 2022

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)