Study of Safety and Biomarker Efficacy of TS23 in Healthy Volunteer

Study Overview
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Brief Summary
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This study is designed to determine the safety, pharmacokinetics and pharmacodynamics of a single intravenous dose of TS23 in healthy adults.

Detailed Description
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This is a first-in-human, Phase 1 study of the safety, pharmacokinetics and pharmacodynamics of TS23 in healthy male volunteers.TS23 is a monoclonal antibody that inactivates alpha 2-antiplasmin. Four dose cohorts of six subjects will be studied in a single ascending dose trial at one clinical center.

Official Title
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Phase 1 Single-ascending Dose-escalation Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Anti-alpha2-antiplasmin (α2AP) Monoclonal Antibody TS23 in Healthy Human Volunteers

Conditions
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Thrombosis, Cerebral Ischemia, Venous Thrombosis, Pulmonary Embolism, Myocardial Infarction

Intervention / Treatment
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* Biological: TS23


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide written informed consent Healthy males age 18 years to 60 years of age Body mass index ≥ 20 and ≤ 33 kg/m squared Exclusion Criteria: Known allergies or hypersensitivities to blood products or derivatives or therapeutic proteins or product excipients or components of CHO cells Current alcohol or drug abuse or history of alcohol or drug abuse Participation in any trial with an investigational drug within 90 days prior to dosing Blood donation of more than 500 mL of blood within 90 days prior to dosing Any history of a bleeding or thrombotic disorder Any history of significant cardiac, pulmonary, renal, hepatic, neurologic, or immunologic disorder Over-the-counter medications, dietary supplements and herbal products (except a daily vitamin) within 14 days of drug administration or during the study No prescription medication for at least 14 days or 5-half-lives, whichever is longer, prior to study drug administration. Use of anticoagulants, fibrinolytic agents or non-steroidal anti-inflammatory medicines (except aspirin doses of 82 mg per day or less) for 2 weeks prior to and during the study Known hereditary fructosemia (due to sorbitol in the formulation) Any previous or current monoclonal antibody therapy History of trauma or surgery within the past 60 days or planned surgery within 30 days Abnormal baseline laboratory values or any laboratory values deemed clinically significant by the Investigator Recent history of head trauma in last 30 days prior to receiving TS23 Unwillingness or inability to avoid contact sports or other activities with more than a small risk of head or facial trauma within 30 days of receiving TS23 History of or risk of falls (e.g., due to dementia, frailty, etc.) Sexually active subjects must agree to use a reliable method of birth control (abstinence, condoms, vasectomy) and to not donate sperm for 3 months after receiving TS23

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Ascending Dose Cohort<br>TS23 | Biological: TS23<br>* comparison of different doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and severity of adverse events post-dose | To count the number and assess the severity of treatment emergent adverse events within 10 weeks post dose | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coagulation (fibrinogen, PT, aPTT) |  | 10 weeks | 
| Anti-drug antibody |  | 16 weeks | 
| alpha2-antiplasmin activity |  | 10 weeks | 
| D-dimer |  | 10 weeks | 
| Pharmacokinetic parameter, maximum concentration of TS23 | Pharmacokinetic parameter Cmax of TS23 in plasma | 10 weeks | 
| Pharmacokinetic parameter, half-life of TS23 | Pharmacokinetic parameter, time required for TS23 concentrations to fall by half | 10 weeks |