A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Phase I Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of GB18 Following Single Subcutaneous Injection in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Number of adverse events as assessed by CTCAE v5.0
研究概览
简要总结
This study is a first-in-human, randomized, double-blind, placebo-controlled, dose-escalation trial in healthy adult participants to evaluate the safety, tolerability, PK, PD, and immunogenicity of GB18.
A total of 36 healthy participants will be enrolled, including 5 dose cohorts (A1-A5) of 50 mg, 100 mg, 200 mg, 400 mg and 600 mg, with 4 participants in Cohort A1, and 8 participants per following cohorts (A2-A5). Participants in each cohort will be randomized to receive GB18 or placebo.
The arms of this study include:
To evaluate the safety and tolerability of GB18 following a single subcutaneous (SC) administered dose in healthy adult participants.
To characterize the serum pharmacokinetics (PK) of GB18 following a single SC administered dose in healthy adult participants.
To characterize the pharmacodynamics (PD) of a single SC administration of GB18 on circulating GDF15 concentrations in healthy adult participants.
To evaluate the immunogenicity profile of GB18 in healthy adult participants. To evaluate the effect of GB18 on body weight in healthy adult participants. To preliminary evaluation of the relationship between GB18 serum concentration and QTc interval after a single SC administration in healthy adult participants.
详细描述
This study is a first-in-human, randomized, double-blind, placebo-controlled, dose-escalation trial in healthy adult participants to evaluate the safety, tolerability, PK, PD, and immunogenicity of GB18.
A total of 36 healthy participants will be enrolled, including 5 dose cohorts (A1-A5) of 50 mg, 100 mg, 200 mg, 400 mg and 600 mg, with 4 participants in Cohort A1, and 8 participants per following cohorts (A2-A5). Participants in each cohort will be randomized to receive GB18 or placebo at a ratio of 3:1, with 3 participants receiving GB18 and 1 participant receiving placebo in Cohort A1, and 6 participants receiving GB18 and 2 participants receiving placebo in the remaining cohorts (A2-A5).
Healthy participants will be screened within 28 days prior to dosing. Participants will be admitted to the Clinical Research Unit (CRU) on Day -1 and receive a single subcutaneous dose of GB18 or placebo on Day 1 at the abdomen. Participants will receive safety assessments on Day 8 and can be discharged with the permission of the investigator. Safety assessments and PK/PD/immunogenicity sampling will be carried out at scheduled timepoints.
The participants will return to the CRU on Day 10, 15, 29, 50, 71, 92, 106 and 127 for blood sampling, safety, and other assessments such as vital signs, ECG, and laboratory test etc.
GB18 will be administered to participants at a starting dose of 50 mg and increasing to 100, 200, 400 and 600 mg in sequential dosing cohorts. The Safety Review Committee (SRC) will assess the safety data, PK data and available PD data at least up to Day 15 (Cohort A1-2)/29 (Cohort A3-5) after the dose administration of each cohort, and a decision of whether to escalate to the next higher dose level or adjust the dose or discontinue dosing will be made by the SRC.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double-blind study and thus the Investigator, Sponsor, Sponsor's delegates (if applicable), and participants are all blinded to treatments. No individual participant information that can be potentially unblinded for the Investigator or participant will be reported until the end of the study.
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
- •Participants who have signed the informed consent form (ICF) prior to the study, fully understand the content, procedures, and possible adverse reactions of the study, and are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
- •Male and female participants aged 18-55 years (inclusive), at the time of signing the ICF.
- •Body weight ≥ 50 kg for males and ≥ 45 kg for females, with a body mass index (BMI = weight (kg)/height 2 (m) 2) of 18.5-26 kg/m2 (inclusive).
- •Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, Vital signs, 12-lead ECG, and laboratory tests.
- •Participants (including their partners) who have no plan to become pregnant and voluntarily use effective contraception from screening to 6 months after the last dose.
排除标准
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
- •History of HIV infection, syphilis, hepatitis B, or hepatitis C; positive testing for HIV, syphilis, HBsAg, or HCVAb.
- •History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody or molecules made of components of monoclonal antibodies.
- •History of recurrent infections or active infections.
- •Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior, or other conditions that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- •Smoking more than five cigarettes per day on average, or habitually used nicotine containing products, or unable to refrain from smoking during the trial.
- •Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention.
- •Exposure to live vaccines within 28 days of screening.
- •Previous administration with an investigational drug within 30 days or marketed or investigational monoclonal antibodies within 3 months or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
- •History of drug abuse within the past 5 years or use of drugs in the 3 months prior to screening, or a positive urine drug test at screening.
- •Screening BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
- •Screening 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline QTcF interval >450 msec, or QRS interval >120 msec). If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values should be used to determine the participant's eligibility.
- •Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary:
- •AST or ALT level ≥1.5 × ULN,
- •Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.
- •History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 3 months of Screening. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 360 mL beer, 45 mL of 40% spirit or 150 mL of wine).
- •Blood donation (excluding plasma donations) of approximately 400 mL or more within 60 days prior to dosing.
- •Participants who, in the judgment of the investigator, are not suitable for participation in the study.
- •Skin scar, rash, or ulceration at the injection site (abdomen).
- •History of vasovagal syncope or needle phobia, and inability to tolerate venous indwelling catheter blood collection.
- •Participants who plan to donate sperm or oocytes within 6 months after administration of the investigational drug.
研究组 & 干预措施
A1-50mg-GB18
干预措施: GB18 injection (Drug)
A1-50mg-placebo
干预措施: Placebo (Drug)
A2-100mg-GB18
干预措施: GB18 injection (Drug)
A2-100mg-placebo
干预措施: Placebo (Drug)
A3-200mg-GB18
干预措施: GB18 injection (Drug)
A3-200mg-placebo
干预措施: Placebo (Drug)
A4-400mg-GB18
干预措施: GB18 injection (Drug)
A4-400mg-placebo
干预措施: Placebo (Drug)
A5-600mg-GB18
干预措施: GB18 injection (Drug)
A5-600mg-placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Number of adverse events as assessed by CTCAE v5.0
时间窗: From pre-dosing to the end of follow-up at 18 weeks
The number of AEs (e.g., abnormalities in laboratory tests, vital signs, physical examinations, and 12-lead ECGs) will be recorded and analyzed.
次要结局
- Serum pharmacokinetics parameters (Cmax, Tmax, AUC0-inf, AUC0-t, λz, t1/2, Vz/F, and CL/F).(From pre-dosing to the end of follow-up at 18 weeks)
- Serum concentrations of total and, if feasible, unbound GDF15 specified in the schedule of activities.(From pre-dosing to the end of follow-up at 18 weeks)
- (if applicable) Incidence of ADA and Nab(From pre-dosing to the end of follow-up at 18 weeks)