Clinical trial NCT06025552: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hemophilia a
Hemophilia B
Blood Coagulation Disorders
Lead sponsor: TiumBio Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-09-06
Enrollment: 40
Sex: MALE
Minimum age (years): 19
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Number and proportion of participants with adverse events
timeFrame: 30 days post-dose
measure: Number of subjects with significant abnormal laboratory values
timeFrame: 30 days post-dose
measure: ADA and Neutralizing antibody results
timeFrame: 30 days post-dose
measure: Number of subjects with significant abnormal Electrocardiography (ECG) findings
timeFrame: 30 days post-dose
measure: Number of subjects With Significant Abnormal vital sign findings
timeFrame: 30 days post-dose
Secondary outcomes:
measure: Pharmacokinetics assessment_Maximum concentration
timeFrame: 4 days post-dose
measure: Pharmacokinetics assessment_AUC last
timeFrame: 4 days post-dose
measure: Pharmacokinetics assessment_AUC inf
timeFrame: 4 days post-dose
measure: Pharmacokinetics assessment_Clearance
timeFrame: 4 days post-dose
measure: Pharmacokinetics assessment_Volume of distribution
timeFrame: 4 days post-dose
measure: Pharmacokinetics assessment_Dose proportionality
timeFrame: 4 days post-dose
measure: Pharmacokinetics assessment_Tmax
timeFrame: 4 days post-dose
measure: Pharmacodynamic assessment_INR change from baseline
timeFrame: 5 days post-dose
measure: Pharmacodynamic assessment_PT change from baseline
timeFrame: 5 days post-dose
measure: Pharmacodynamic assessment_aPTT change from baseline
timeFrame: 5 days post-dose
measure: Pharmacokinetics assessment_incremental recovery
timeFrame: 4 days post-dose
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
References: