Study of Safety and Biomarker Efficacy of TS23 in Healthy Volunteer (TS23Phase1a)

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

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

Study Overview

• Status: Unknown
• Conditions: Myocardial Infarction; Thrombosis; Venous Thrombosis; Pulmonary Embolism; Cerebral Ischemia
• Intervention / Treatment: Biological: TS23

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Ascending Dose Cohort; TS23	Biological: TS23; comparison of different doses

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Translational Sciences, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): June 1, 2016
• Study Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: November 11, 2016
• First Submitted That Met QC Criteria: December 20, 2016
• First Posted (Estimate): December 23, 2016

Study Record Updates

• Last Update Posted (Estimate): December 23, 2016
• Last Update Submitted That Met QC Criteria: December 20, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Stroke; Brain Infarction; Myocardial Infarction; Infarction; Brain Ischemia; Embolism; Ischemia; Thrombosis; Venous Thrombosis; Cerebral Infarction; Pulmonary Embolism
• Other Study ID Numbers: TS CP01-2015