Clinical trial NCT04742062: First in Human Clinical Trial of ApTOLL in Healthy Volunteers
Official title: First in Human Dose Ascending, Randomized, Placebo-Controlled Clinical Trial to Assess Tolerability and Pharmacokinetics of ApTOLL in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Stroke
Keywords: Healthy volunteers
ApTOLL
Lead sponsor: aptaTargets S.L.
Sponsor class: INDUSTRY
Collaborators: name: Ministry of Science and Innovation, Spain
name: Anagram
First posted: 2021-02-05
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Adverse Events as assessed by CTCAE v4.0
timeFrame: From dosing to follow-up (day 15 after dosing)
measure: Peak Plasma Concentration
timeFrame: Predose and at different times up to 72 hours post-dose
measure: Area under the plasma concentration
timeFrame: Predose and at different times up to 72 hours post-dose
Secondary outcomes:
measure: Vital signs
timeFrame: From screening to follow-up (day 15 after dosing)
measure: Vital signs
timeFrame: From screening to follow-up (day 15 after dosing)
measure: Vital signs
timeFrame: From screening to follow-up (day 15 after dosing)
measure: Vital signs
timeFrame: From screening to follow-up (day 15 after dosing)
measure: Laboratory determinations
timeFrame: From screening to follow-up (day 15 after dosing)
measure: Laboratory determinations
timeFrame: From screening to follow-up (day 15 after dosing)
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Clinical Pharmacology Department. Hospital Universitario de La Princesa
Study officials:
affiliation: Clinical Trials Unit. Hospital Universitario La Princesa
name: Dolores Ochoa, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: aptaTargets S.L.
name: Macarena Hernández, PhD
role: STUDY_DIRECTOR
References:
citation: 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.