First in Human Clinical Trial of ApTOLL in Healthy Volunteers

Stroke Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04742062
• Other study ID #: ApTOLL-FIH-01
• Status: Completed
• Phase: Phase 1
• Start date: July 18, 2019
• Est. completion date: March 20, 2020

Study information

• Verified date: January 2021
• Source: aptaTargets S.L.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: March 20, 2020
• Est. primary completion date: February 27, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Stroke

Intervention

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.

Other:
• Placebo
100 mL 0.9% Sodium Chloride solution

Locations

Country	Name	City	State
Spain	Clinical Pharmacology Department. Hospital Universitario de La Princesa	Madrid

Sponsors (3)

Lead Sponsor	Collaborator
aptaTargets S.L.	Anagram, Science and Innovation Spanish Ministry

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Peak Plasma Concentration	Peak Plasma Concentration (Cmax)	Predose and at different times up to 72 hours post-dose
Primary	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	Vital signs	Heart Rate	From screening to follow-up (day 15 after dosing)
Secondary	Vital signs	Blood Presure	From screening to follow-up (day 15 after dosing)
Secondary	Vital signs	Respiratory Rate	From screening to follow-up (day 15 after dosing)
Secondary	Vital signs	Body Temperature	From screening to follow-up (day 15 after dosing)
Secondary	Laboratory determinations	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)
Secondary	Laboratory determinations	Number of patients with treatment-related alterations Complement Factors activation determined in blood	From screening to follow-up (day 15 after dosing)

External Links

•   Biotechnology company specialized in therapeutic aptamers