A Randomized, Double-Blind, Placebo-Controlled, Ascending Single and Multiple Dose First in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ANXV Administered as an Intravenous Infusion to Healthy Male Subjects
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Healthy
- Sponsor
- Annexin Pharmaceuticals AB
- Enrollment
- 46
- Locations
- 1
- Primary Endpoint
- Seriousness of adverse events.
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is an adaptive, randomised, double-blind, single-centre, placebo-controlled phase I, First in Human study designed to evaluate the safety, tolerability and pharmacokinetics of single and multiple intravenous dosing of ANXV in healthy male subjects.
Detailed Description
This First in Human study is divided in two parts. Part I, Single Ascending Dose (SAD), will explore safety, tolerability and PK of single intravenous doses of ANXV. Part II, Multiple Ascending Dose (MAD), will explore safety, tolerability and PK of multiple doses (five consecutive daily doses) of intravenous ANXV. The objectives of this study are: Primary objective: - To evaluate the safety and tolerability of single/multiple ascending doses of ANXV in healthy male subjects. Secondary objective: - To determine the PK profile of single/multiple ascending doses of ANXV in healthy male subjects. Exploratory objectives: - To evaluate ADA to ANXV and other relevant parameters.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing and able to give written informed consent for participation in the study.
- •Healthy male subject aged 18-50 years inclusive at screening.
- •BMI ≥ 18.0 and ≤ 30.0 kg/m2 and weight at least 50 kg and no more than 100 kg at screening.
- •Overtly healthy based on medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator.
- •Male subjects must be willing to use condom or be vasectomised or practice sexual abstinence to prevent pregnancy and drug exposure of a partner, and refrain from donating sperm from the date of dosing until 3 months after (last) dosing with the IMP. Their female partner of child-bearing potential are expected to use contraceptive methods with a failure rate of \< 1% to prevent pregnancy (combined \[oestrogen and progestogen containing\] hormonal contraception associated with inhibition of ovulation \[oral, intravaginal, transdermal\], progestogen-only hormonal contraception associated with inhibition of ovulation \[oral, injectable, implantable\], intrauterine device \[IUD\] or intrauterine hormone-releasing system \[IUS\]).
Exclusion Criteria
- •History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
- •Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP.
- •Malignancy within the past 5 years with the exception of in situ removal of basal cell carcinoma.
- •Any planned major surgery within the duration of the study.
- •Any positive result on screening for serum hepatitis B surface antigen (HbsAg), hepatitis C antibody and Human Immunodeficiency Virus (HIV).
- •History of thromboembolic events.
- •History of significant bleeding (gross haematuria, haemoptysis, gastrointestinal tract bleeding).
- •Evidence or history of a hypercoagulable state (e.g. shortened APTT).
- •Prior exposure to recombinant Annexin A5 (for diagnostic purposes).
- •Any history of coronary artery disease or cerebrovascular accident.
Outcomes
Primary Outcomes
Seriousness of adverse events.
Time Frame: From day 1 (inclusion) until day 35
Seriousness of adverse events at single and multiple ascending doses of ANXV.
Intensity of adverse events.
Time Frame: From day 1 (inclusion) until day 35
Intensity of adverse events at single and multiple ascending doses of ANXV.
Frequency of adverse events.
Time Frame: From day 1 (inclusion) until day 35
Frequency of adverse events at single and multiple ascending doses of ANXV.
Secondary Outcomes
- PK profile of single and multiple ascending doses of ANXV: Tmax(0-24hours after IMP administration)
- PK profile of single and multiple ascending doses of ANXV: λz(0-24hours after IMP administration)
- PK profile of single and multiple ascending doses of ANXV: CL(0-24hours after IMP administration)
- PK profile of single and multiple ascending doses of ANXV: Fraction excreted in urine (fe)(0-24hours after IMP administration)
- PK profile of single and multiple ascending doses of ANXV: Cmax(0-24hours after IMP administration)
- PK profile of single and multiple ascending doses of ANXV: AUClast(0-24hours after IMP administration)
- PK profile of single and multiple ascending doses of ANXV: T½(0-24hours after IMP administration)
- PK profile of single and multiple ascending doses of ANXV: Vz(0-24hours after IMP administration)