A Phase 1 Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of TL-003 in Healthy Adult Participants and Open-label Assessments in Participants With Ulcerative Colitis
概览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- TrueLab Biopharmaceutical Co., Ltd
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Incidence and severity of Treatment Emergent Adverse Events adverse events (TEAEs)
概览
简要总结
The goal of this study is to evaluate safety, tolerability, pharmacokinetics (PK)), pharmacodynamics (PD) and immunogenicity of single and multiple ascending dose of TL-003 in healthy adult participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double blind
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female between 18 and 55 years of age.
- •Body mass index (BMI) between 18.0 to 32.0 kg/m2 (inclusive), Body weight ≥ 50 kg for males and ≥ 45 kg for females.
- •Able to participate and comply with all study procedures and restrictions, and willing to provide written informed consent to participate in the study.
- •Female participants who are not pregnant or breastfeeding and meet at least one of the following conditions:
- •Not of childbearing potential
- •Of childbearing potential and agrees to use a highly effective method of contraception plus condom use consistently from 30 days prior to Day 1 until the EOS visit.
- •Should not donate ova from Day 1 until the EOS Visit.
- •Male participants must use condom if sexually active with females of childbearing potential from Day 1 until the EOS visit. The female partner of a male participant who does not meet the definition of postmenopausal or permanently surgically sterile is considered of childbearing potential and is required to use a highly effective method of contraception consistently from 30 days prior to Day 1 until the EOS visit of the male participant. Male participants who are surgically sterilized, performed at least 6 months prior to screening, may be enrolled. Male participants must also agree not to donate sperm from Day 1 until the EOS visit.
- •No clinically significant findings as determined by medical history, and by results of physical examination, vital signs, electrocardiogram (ECG), and clinical laboratory tests obtained within 28 days prior to study treatment administration.
排除标准
- •History or presence of any clinically significant organ system disease that could interfere with the objectives of the study or the safety of the participants.
- •History of immunological abnormality (i.e., primary or secondary immune suppression) that could interfere with the objectives of the study or the safety of the participants.
- •Presence or history of any abnormality or illness, which in the opinion of the Investigator (or designee) may affect absorption, distribution, metabolism or elimination of the study treatment.
- •Any screening laboratory evaluation outside the laboratory reference range that is judged by the Investigator (or designee) to be clinically significant, including but not limited to:
- •Participants with estimated glomerular filtration rate (eGFR) \< 80 mL/min/1.73m2 as determined by the CKD-EPI 2021 formula, at the Screening or Baseline visits.
- •Alanine amino transferase (ALT) or aspartate amino transferase (AST) \>1.5 times upper limit of normal (ULN), which remains similar upon repeat, at the Screening or Baseline visits.
- •Total bilirubin \> 1.5 × ULN at the Screening or Baseline visits. Total bilirubin \> 1.5 × ULN is acceptable if, direct bilirubin \< 40%, normal AST/ALT/ alkaline phosphatase (ALP), and no evidence of hemolysis, according to Investigator (or designee) discretion.
- •White blood cell count \< 3,000 cells/mm3 (\< 3.0×10 9/L) or any abnormal evaluations judged clinically significant by the Investigator (or designee) at the Screening or Baseline visits. Note: If the test results meet the above criteria, a repeat test may be performed to determine eligibility.
- •Blood pressure and heart rate are outside the ranges 90-140 mmHg systolic, 50-90 mmHg diastolic, heart rate 40-100 beats/min.
- •12-lead ECG with any abnormality judged by the Investigator (or designee) to be clinically significant, or QTcF interval of \> 450 msec for men or \> 470 msec for women.
研究组 & 干预措施
SAD Cohort 1
8 participants will receive in a 3:1 ratio of a single dose of SAD Dose Level 1 of TL-003 or placebo.
干预措施: TL-003 (Drug)
SAD Cohort 1
8 participants will receive in a 3:1 ratio of a single dose of SAD Dose Level 1 of TL-003 or placebo.
干预措施: Placebo (Drug)
SAD Cohort 2
8 participants will receive in a 3:1 ratio of a single dose of SAD Dose Level 2 of TL-003 or placebo.
干预措施: TL-003 (Drug)
SAD Cohort 2
8 participants will receive in a 3:1 ratio of a single dose of SAD Dose Level 2 of TL-003 or placebo.
干预措施: Placebo (Drug)
SAD Cohort 3
8 participants will receive in a 3:1 ratio of a single dose of SAD Dose Level 3 of TL-003 or placebo.
干预措施: TL-003 (Drug)
SAD Cohort 3
8 participants will receive in a 3:1 ratio of a single dose of SAD Dose Level 3 of TL-003 or placebo.
干预措施: Placebo (Drug)
SAD Cohort 4
8 participants will receive in a 3:1 ratio of a single dose of SAD Dose Level 4 of TL-003 or placebo.
干预措施: TL-003 (Drug)
SAD Cohort 4
8 participants will receive in a 3:1 ratio of a single dose of SAD Dose Level 4 of TL-003 or placebo.
干预措施: Placebo (Drug)
MAD Cohort 1
8 participants will receive in a 3:1 ratio of a single dose of MAD Dose Level 1 of TL-003 or placebo.
干预措施: TL-003 (Drug)
MAD Cohort 1
8 participants will receive in a 3:1 ratio of a single dose of MAD Dose Level 1 of TL-003 or placebo.
干预措施: Placebo (Drug)
MAD Cohort 2
8 participants will receive in a 3:1 ratio of a single dose of MAD Dose Level 2 of TL-003 or placebo.
干预措施: TL-003 (Drug)
MAD Cohort 2
8 participants will receive in a 3:1 ratio of a single dose of MAD Dose Level 2 of TL-003 or placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence and severity of Treatment Emergent Adverse Events adverse events (TEAEs)
时间窗: Up to 169 Days
Incidence and severity of AEs, including clinical relevant findings from the clinical laboratory tests (hematology, urinalysis, blood chemistry), physical examination, vital signs, 12-lead ECGs.
次要结局
- Time to maximum concentration (Tmax)(Up to 169 Days)
- Maximum concentration (Cmax)(Up to 169 Days)
- Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-t)(Up to 169 Days)
- Area under the concentration-time curve from time 0 to infinity (AUC0-inf)(Up to 169 Days)
- Terminal half-life (t1/2)(Up to 169 Days)
- Apparent clearance (CL)(Up to 169 Days)
- Apparent volume of distribution (Vz)(Up to 169 Days)
- Terminal elimination rate constant (λz)(Up to 169 Days)
- Percentage of AUC0-inf obtained by extrapolation (%AUCex)(Up to 169 Days)
- Accumulation ratio (Rac)(Up to 169 Days)