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Study of TU7710 in Warfarin Anti-coagulated Healthy Male Subjects

Primary Purpose

Hemophilia A, Hemophilia B, Blood Coagulation Disorders

Status
Recruiting
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
TU7710
Normal saline
Sponsored by
TiumBio Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophilia A

Eligibility Criteria

19 Years - 45 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria: Age ≥19 and ≤45 BMI of ≥18.0 kg/m2 and ≤30.0 kg/m2 Body weight of ≥55.0 kg and ≤90.0 kg Provide informed consent and willing to comply with study requirements. Exclusion Criteria: History or at risk of developing diseases related to venous thromboembolic events or has family history of such disease History of major bleeding/traumatic event or major surgery within 6 month History of any other clinically relevant coagulation disorder (such as gastrointestinal bleeding, hemorrhoid hemorrhage) Abnormal coagulation related laboratory abnormal test results, including protein C, protein S, PT, aPTT history or current symptoms of gastrointestinal, liver, or renal disease that may affect the pharmacokinetics of the IP History of or are currently with hepatitis B or C (active or carrier state) or human immunodeficiency virus (HIV) or syphilis infection. Currently smoking or have smoked within 1 month before IP or positive cotinine results History of alcohol abuse or positive alcohol breath test Excessive caffeine intake within 7 days before IP INR results not between 2.0~3.0 range after warfarin treatment History of hypersensitivity to medicinal product similar to TU7710 active ingredient or excipient Laboratory abnormal test results, such as QTcF <340msec or >450msec (or family history of long QT syndrome), LDL >190mg/dl , Total cholesterol >300mg/dl, triglycerides > 350mg/dl, ALT >1.5*ULN, AST >1.5*ULN, bilirubin >1.5*ULN Abnormal vital sign SBP >140mmHG, DBP <90mmHg, heart rate <40bpm or >85bpm Any medical history that may increase the risk or affect the evaluation of study objectives by participating in this study at the discretion of the investigator. (e.g., neurology or psychiatric history)

Sites / Locations

  • Seoul National University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

TU7710

Normal Saline (placebo of TU7710)

Arm Description

TU7710 of escalating 5 doses

Placebo of TU7710 at corresponding TU7710 dose level

Outcomes

Primary Outcome Measures

Number and proportion of participants with adverse events
Number and proportion of participants with adverse events/ adverse reaction /SAE overall and by treatment group
Number of subjects with significant abnormal laboratory values
Mean with standard deviation, median, maximum, minimum results of laboratory values in each treatment group. The laboratory parameters that will be assessed are clinical chemistry, hematology and urinalysis.
ADA and Neutralizing antibody results
Incidence of subjects with ADA and Nab positive results
Number of subjects with significant abnormal Electrocardiography (ECG) findings
Mean with standard deviation, median, maximum, minimum results of ECG results in each treatment group. The ECG parameters that will be assessed are heart rate, PR interval, QRS interval, QT interval, and QTcF interval.
Number of subjects With Significant Abnormal vital sign findings
Mean with standard deviation, median, maximum, minimum results of vital sign values in each treatment group. The vital signs that will be assessed are body temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.

Secondary Outcome Measures

Pharmacokinetics assessment_Maximum concentration
Maximum plasma VIIa activity level in each dose level
Pharmacokinetics assessment_AUC last
Area under plasma activity-time curve after TU7710 single administration from time zero to last quantifiable concentration
Pharmacokinetics assessment_AUC inf
Area Under the Plasma activity-time curve after TU7710 single administration From Time Zero Extrapolated to Infinity
Pharmacokinetics assessment_Clearance
Clearance after TU7710 single administration
Pharmacokinetics assessment_Volume of distribution
Volume of distribution after TU7710 single administration
Pharmacokinetics assessment_Dose proportionality
Regression analysis using the power model between the log-converted Cmax, AUClast, and the log-converted dose can be performed, and each parameter adjusted by dose can be calculated and compared between the dose groups
Pharmacokinetics assessment_Tmax
Time from administration to maximum plasma VIIa level in each dose level
Pharmacodynamic assessment_INR change from baseline
INR measurement change from baseline to day 5 in each treatment group and dose level
Pharmacodynamic assessment_PT change from baseline
PT measurement change from baseline to day 5 in each treatment group and dose level
Pharmacodynamic assessment_aPTT change from baseline
aPTT measurement change from baseline to day 5 in each treatment group and dose level
Pharmacokinetics assessment_incremental recovery
Incremental recovery after TU7710 single administration expressed as the ratio of measured peak level against dose per bodyweight

Full Information

First Posted
July 31, 2023
Last Updated
September 8, 2023
Sponsor
TiumBio Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT06025552
Brief Title
Study of TU7710 in Warfarin Anti-coagulated Healthy Male Subjects
Official Title
A First-in-Human (FIH), Randomized, Double-Blind, Placebo-controlled, Phase 1a Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Activity of TU7710 Following Single, Ascending, Intravenous, Dose Administration in Warfarin Anti-coagulated Healthy Male Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 2, 2023 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
February 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
TiumBio Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a Phase 1a, double-blind, randomized, placebo- controlled, SAD study to assess safety, tolerability, PK, and PD of TU7710 in warfarin treated healthy male participants.
Detailed Description
The 40 subjects will be divided into 5 cohorts, and the subjects assigned to each cohort will be randomly assigned with 6 persons receiving TU7710 and 2 persons receiving a placebo for TU7710. Each cohort will proceed in sequence and the next cohort study will be decided by the Safety Monitoring Committee (SMC) . Subjects will be participated in the study after warfarin anti-coagulation to maintain the INR between 2.00 and 3.00 as a preventive measure for potential thrombosis prior to the IP administration.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A, Hemophilia B, Blood Coagulation Disorders

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
5 cohorts with 5 dose levels will sequentially be escalated after safety review. 8 subjects in each cohort who will be randomly assigned to placebo or TU7710 group in 2:6 ratio.
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TU7710
Arm Type
Experimental
Arm Description
TU7710 of escalating 5 doses
Arm Title
Normal Saline (placebo of TU7710)
Arm Type
Placebo Comparator
Arm Description
Placebo of TU7710 at corresponding TU7710 dose level
Intervention Type
Drug
Intervention Name(s)
TU7710
Intervention Description
In each dose level, 6 subjects will be assigned to TU7710. Anticipated escalating dose levels are 100mcg/kg, 200mcg/kg, 400mcg/kg, 800mcg/kg and the last dose will be decided after assessing cohort 1~4 PK, PD, safety, and exploratory efficacy data.
Intervention Type
Drug
Intervention Name(s)
Normal saline
Intervention Description
Placebo of TU7710 at corresponding TU7710 dose level. In each dose level, 2 subjects will be assigned to placebo group.
Primary Outcome Measure Information:
Title
Number and proportion of participants with adverse events
Description
Number and proportion of participants with adverse events/ adverse reaction /SAE overall and by treatment group
Time Frame
30 days post-dose
Title
Number of subjects with significant abnormal laboratory values
Description
Mean with standard deviation, median, maximum, minimum results of laboratory values in each treatment group. The laboratory parameters that will be assessed are clinical chemistry, hematology and urinalysis.
Time Frame
30 days post-dose
Title
ADA and Neutralizing antibody results
Description
Incidence of subjects with ADA and Nab positive results
Time Frame
30 days post-dose
Title
Number of subjects with significant abnormal Electrocardiography (ECG) findings
Description
Mean with standard deviation, median, maximum, minimum results of ECG results in each treatment group. The ECG parameters that will be assessed are heart rate, PR interval, QRS interval, QT interval, and QTcF interval.
Time Frame
30 days post-dose
Title
Number of subjects With Significant Abnormal vital sign findings
Description
Mean with standard deviation, median, maximum, minimum results of vital sign values in each treatment group. The vital signs that will be assessed are body temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.
Time Frame
30 days post-dose
Secondary Outcome Measure Information:
Title
Pharmacokinetics assessment_Maximum concentration
Description
Maximum plasma VIIa activity level in each dose level
Time Frame
4 days post-dose
Title
Pharmacokinetics assessment_AUC last
Description
Area under plasma activity-time curve after TU7710 single administration from time zero to last quantifiable concentration
Time Frame
4 days post-dose
Title
Pharmacokinetics assessment_AUC inf
Description
Area Under the Plasma activity-time curve after TU7710 single administration From Time Zero Extrapolated to Infinity
Time Frame
4 days post-dose
Title
Pharmacokinetics assessment_Clearance
Description
Clearance after TU7710 single administration
Time Frame
4 days post-dose
Title
Pharmacokinetics assessment_Volume of distribution
Description
Volume of distribution after TU7710 single administration
Time Frame
4 days post-dose
Title
Pharmacokinetics assessment_Dose proportionality
Description
Regression analysis using the power model between the log-converted Cmax, AUClast, and the log-converted dose can be performed, and each parameter adjusted by dose can be calculated and compared between the dose groups
Time Frame
4 days post-dose
Title
Pharmacokinetics assessment_Tmax
Description
Time from administration to maximum plasma VIIa level in each dose level
Time Frame
4 days post-dose
Title
Pharmacodynamic assessment_INR change from baseline
Description
INR measurement change from baseline to day 5 in each treatment group and dose level
Time Frame
5 days post-dose
Title
Pharmacodynamic assessment_PT change from baseline
Description
PT measurement change from baseline to day 5 in each treatment group and dose level
Time Frame
5 days post-dose
Title
Pharmacodynamic assessment_aPTT change from baseline
Description
aPTT measurement change from baseline to day 5 in each treatment group and dose level
Time Frame
5 days post-dose
Title
Pharmacokinetics assessment_incremental recovery
Description
Incremental recovery after TU7710 single administration expressed as the ratio of measured peak level against dose per bodyweight
Time Frame
4 days post-dose

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Age ≥19 and ≤45 BMI of ≥18.0 kg/m2 and ≤30.0 kg/m2 Body weight of ≥55.0 kg and ≤90.0 kg Provide informed consent and willing to comply with study requirements. Exclusion Criteria: History or at risk of developing diseases related to venous thromboembolic events or has family history of such disease History of major bleeding/traumatic event or major surgery within 6 month History of any other clinically relevant coagulation disorder (such as gastrointestinal bleeding, hemorrhoid hemorrhage) Abnormal coagulation related laboratory abnormal test results, including protein C, protein S, PT, aPTT history or current symptoms of gastrointestinal, liver, or renal disease that may affect the pharmacokinetics of the IP History of or are currently with hepatitis B or C (active or carrier state) or human immunodeficiency virus (HIV) or syphilis infection. Currently smoking or have smoked within 1 month before IP or positive cotinine results History of alcohol abuse or positive alcohol breath test Excessive caffeine intake within 7 days before IP INR results not between 2.0~3.0 range after warfarin treatment History of hypersensitivity to medicinal product similar to TU7710 active ingredient or excipient Laboratory abnormal test results, such as QTcF <340msec or >450msec (or family history of long QT syndrome), LDL >190mg/dl , Total cholesterol >300mg/dl, triglycerides > 350mg/dl, ALT >1.5*ULN, AST >1.5*ULN, bilirubin >1.5*ULN Abnormal vital sign SBP >140mmHG, DBP <90mmHg, heart rate <40bpm or >85bpm Any medical history that may increase the risk or affect the evaluation of study objectives by participating in this study at the discretion of the investigator. (e.g., neurology or psychiatric history)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Heeyeon Jung
Phone
031-600-1500
Ext
1513
Email
tiumbio@tiumbio.com
Facility Information:
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kyung Sang Yoo, M.D, Ph.D

12. IPD Sharing Statement

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Study of TU7710 in Warfarin Anti-coagulated Healthy Male Subjects

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