Study of TU7710 in Warfarin Anti-coagulated Healthy Male Subjects

Hemophilia A Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06025552
• Other study ID #: TUB4PI-01
• Status: Recruiting
• Phase: Phase 1
• Start date: August 2, 2023
• Est. completion date: February 2024

Study information

• Verified date: August 2023
• Source: TiumBio Co., Ltd.
• Contact: Heeyeon Jung
• Phone: 031-600-1500
• Email: tiumbio[@]tiumbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: February 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 19 Years to 45 Years

Eligibility

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)

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Hemophilia A
• Hemophilia B
• Hemostatic Disorders

Intervention

Drug:
• TU7710
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.
• Normal saline
Placebo of TU7710 at corresponding TU7710 dose level. In each dose level, 2 subjects will be assigned to placebo group.

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
TiumBio Co., Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and proportion of participants with adverse events	Number and proportion of participants with adverse events/ adverse reaction /SAE overall and by treatment group	30 days post-dose
Primary	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.	30 days post-dose
Primary	ADA and Neutralizing antibody results	Incidence of subjects with ADA and Nab positive results	30 days post-dose
Primary	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.	30 days post-dose
Primary	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.	30 days post-dose
Secondary	Pharmacokinetics assessment_Maximum concentration	Maximum plasma VIIa activity level in each dose level	4 days post-dose
Secondary	Pharmacokinetics assessment_AUC last	Area under plasma activity-time curve after TU7710 single administration from time zero to last quantifiable concentration	4 days post-dose
Secondary	Pharmacokinetics assessment_AUC inf	Area Under the Plasma activity-time curve after TU7710 single administration From Time Zero Extrapolated to Infinity	4 days post-dose
Secondary	Pharmacokinetics assessment_Clearance	Clearance after TU7710 single administration	4 days post-dose
Secondary	Pharmacokinetics assessment_Volume of distribution	Volume of distribution after TU7710 single administration	4 days post-dose
Secondary	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	4 days post-dose
Secondary	Pharmacokinetics assessment_Tmax	Time from administration to maximum plasma VIIa level in each dose level	4 days post-dose
Secondary	Pharmacodynamic assessment_INR change from baseline	INR measurement change from baseline to day 5 in each treatment group and dose level	5 days post-dose
Secondary	Pharmacodynamic assessment_PT change from baseline	PT measurement change from baseline to day 5 in each treatment group and dose level	5 days post-dose
Secondary	Pharmacodynamic assessment_aPTT change from baseline	aPTT measurement change from baseline to day 5 in each treatment group and dose level	5 days post-dose
Secondary	Pharmacokinetics assessment_incremental recovery	Incremental recovery after TU7710 single administration expressed as the ratio of measured peak level against dose per bodyweight	4 days post-dose