First in Human Clinical Trial of ApTOLL in Healthy Volunteers

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:

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

Inclusion criteria

• 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.

Exclusion criteria

• 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.
• History of sensitivity to any drug.
• Having donated blood in the last month before start of the study.
• Any reason or opinion of the investigator that would prevent the subject from participation in the study.
• Inability to follow the instructions or an unwillingness to collaborate during the study.