First in Human Clinical Trial of ApTOLL in Healthy Volunteers

Phase 1

Completed

• Conditions: Stroke
• Interventions: Other: Placebo; Drug: ApTOLL

• Registration Number: NCT04742062
• Lead Sponsor: aptaTargets S.L.

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.

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 Timeline

• Study Start: 2019-07-18
• Primary Completion: 2020-02-27
• Study Completion: 2020-03-20
• Status Verified: 2021-01
• Study First Submitted: 2021-01-26
• Study First Submitted QC: 2021-02-04
• Study First Posted: 2021-02-05
• Last Update Submitted: 2022-03-16
• Last Update Posted: 2022-03-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo single dose	Placebo	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).
Placebo multiple dose	Placebo	Placebo is administered intravenously every eight hours during 24h. This arm includes twosubjects (1 sentinel + 1 subject).
ApTOLL multiple dose	ApTOLL	ApTOLL is administered intravenously every eight hours during 24h (21mg). This arm includes six subjects (1 sentinel + 5 subjects).
ApTOLL single dose	ApTOLL	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).

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Laboratory determinations	From screening to follow-up (day 15 after dosing)	Number of patients with treatment-related alterations Complement Factors activation determined in blood
Vital signs	From screening to follow-up (day 15 after dosing)	Body Temperature

Trial Locations

Locations (1)

Clinical Pharmacology Department. Hospital Universitario de La Princesa; 🇪🇸 Madrid, Spain