An Exploratory Multicenter, Open-label, Sequential Cohort Study to Evaluate the Preliminary Efficacy, Safety, and Pharmacokinetic Characteristics of LP-98 forInjection in Antiretroviral Therapy-Naive HIV-Infected Individuals
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Plasma HIV RNA levels (log10 copies/mL) and changes from baseline
研究概览
简要总结
An Exploratory Multicenter, Open-label, Sequential Cohort Study to Evaluate the Preliminary Efficacy, Safety, and Pharmacokinetic Characteristics of LP-98 for Injection in Antiretroviral Therapy-Naive HIV-Infected Individuals
详细描述
The study utilizes a sequential cohort design, with three dosage cohorts (20 mg, 40 mg, 80 mg). The cohorts will be enrolled sequentially from low to high doses, with the next dose group initiating subject screening and enrollment after the last subject in the previous cohort has been enrolled.
The study plans to enroll a total of 30 subjects, with 10 subjects in each cohort. Enrolled subjects will receive LP-98 treatment at doses of 20 mg, 40 mg, or 80 mg according to their assigned cohort. The drug will be administered via subcutaneous injection, with an interval of 14 days between doses, for a total of 4 doses.
The study includes a screening phase (D-28 to D-1), a treatment phase (D1 to D57), and a follow-up phase (D58 to D71). The total duration of participation for each subject is approximately 99 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject must voluntarily agree to participate in the study and provide informed consent before undergoing any study-related assessments.
- •At the time of screening, the subject must be between 18 and 65 years of age (inclusive), either male or female.
- •At the time of screening, male subjects must weigh at least 50 kg, and female subjects must weigh at least 45 kg.
- •Plasma HIV RNA levels must be ≥1000 copies/mL, and CD4+ T lymphocyte count must be ≥200 cells/μL.
- •For Female Subjects: Only non-reproductive females will be included, which includes those who have undergone surgical sterilization (documented hysterectomy or bilateral oophorectomy) at least 6 weeks prior to the screening visit, or those who have been postmenopausal for at least 12 months (confirmed by a follicle-stimulating hormone (FSH) level ≥40 IU/L).
- •For Male Subjects with Fertile Female Partners: The subject must agree to use a non-pharmacological contraception method for 14 days prior to dosing, during the study, and for 3 months following the administration of the study drug. Male subjects must not donate sperm during this period.
- •The subject must be willing to adhere to the study protocol, including visits, study treatment, laboratory tests, and other study-related procedures and requirements.
排除标准
- •Known allergy to the study drug or its excipients, or a history of severe allergic reactions (including any food allergies or drug allergies).
- •Has previously received antiviral therapy (ART) or has been vaccinated against HIV.
- •A history of severe disease or the presence of other severe chronic conditions.
- •A history of mental health disorders or a family history of psychiatric diseases.
- •Any of the Following Conditions:
- •1）Persistent unexplained fever above 38°C within 1 month prior to screening or during the screening phase.
- •2）Persistent diarrhea (more than 3 bowel movements per day) within 1 month prior to screening or during the screening phase.
- •3）Severe infections, opportunistic infections, or sepsis within 6 months prior to screening or during the screening phase.
- •6、Positive for hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCV-Ab).
- •7、Abnormal 12-lead electrocardiogram (ECG) findings with clinical significance at screening, such as a male QTcF interval (Fridericia correction formula) > 450 ms, or female QTcF > 470 ms.
- •8、Elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 times the upper limit of normal (ULN), or total bilirubin > 1.5 times ULN at screening.
- •9、Serum creatinine clearance (Ccr) < 60 mL/min at screening (calculated using the Cockcroft-Gault formula).
- •10、Known or suspected history of drug abuse (including morphine, methamphetamine, ketamine, dimethylthioamphetamine, tetrahydrocannabinolic acid, cocaine), or a positive baseline drug screening test.
- •11、A history of alcohol abuse within the past year (defined as consuming more than 14 standard units of alcohol per week, where 1 standard unit is 14 g of alcohol, equivalent to 360 mL of 5% beer, 45 mL of 40% liquor, or 120 mL of 12% wine), or inability to comply with the study's alcohol prohibition during the study.
- •12、Smoking more than 5 cigarettes per day within the last 3 months prior to screening, or inability to comply with the study's smoking prohibition during the study.
- •13、Receiving any vaccine within 3 months prior to screening, or planning to receive any vaccine during the study.
- •14、Received any investigational drug treatment or participated in any drug/device trial (excluding in vitro diagnostic devices) within 3 months prior to dosing.
- •15、Major surgery within 30 days prior to dosing, or planned major surgery during the study.
- •16、Blood donation or loss of ≥ 400 mL within 3 months prior to screening, or receiving a blood transfusion during this period.
- •17、Any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in this study.
研究组 & 干预措施
LP-98 20 mg dose group
A total of 10 subjects are planned to be enrolled in this cohort, and each enrolled subject will receive a 20 mg dose of LP-98 per administration. The drug will be administered via subcutaneous injection at an interval of 14 days, for a total of 4 administrations.
干预措施: LP-98 20 mg (Drug)
LP-98 40 mg dose group
A total of 10 subjects are planned to be enrolled in this cohort, and each enrolled subject will receive a 40 mg dose of LP-98 per administration. The drug will be administered via subcutaneous injection at an interval of 14 days, for a total of 4 administrations.
干预措施: LP-98 40 mg (Drug)
LP-98 80 mg dose group
A total of 10 subjects are planned to be enrolled in this cohort, and each enrolled subject will receive a 80 mg dose of LP-98 per administration. The drug will be administered via subcutaneous injection at an interval of 14 days, for a total of 4 administrations.
干预措施: LP-98 80 mg (Drug)
结局指标
主要结局
Plasma HIV RNA levels (log10 copies/mL) and changes from baseline
时间窗: Within 71 days after the first administration.
Changes of HIV viral load detection will be recorded.
Proportion of subjects with plasma HIV RNA < 50 copies/mL
时间窗: Within 71 days after the first administration.
Changes of HIV viral load detection will be recorded.
Proportion of subjects with plasma HIV RNA < 200 copies/mL
时间窗: Within 71 days after the first administration.
Changes of HIV viral load detection will be recorded.
Absolute CD4+ T lymphocyte count and change from baseline
时间窗: Within 71 days after the first administration.
Changes of CD4+T counts will be recorded.
CD4+/CD8+ T lymphocyte ratio and change from baseline
时间窗: Within 71 days after the first administration.
Changes of CD4+/CD8+ T counts will be recorded.
次要结局
- Changes from baseline in respiration rate of Vital Signs.(Within 71 days after the first administration.)
- Changes from baseline in blood pressure of Vital Signs.(Within 71 days after the first administration.)
- Changes from baseline in Blood lactate of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in body temperature of Vital Signs.(Within 71 days after the first administration.)
- Changes from baseline in red blood cell count of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in white blood cell count of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in neutrophil count of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in lymphocyte count of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in platelet count of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in hemoglobin of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in PT of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in INR of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in APTT of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in total bilirubin of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in direct bilirubin of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in ALT of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in AST of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in total protein of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in albumin of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in urea of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in creatinine of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in uric acid of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in glucose of Laboratory Examination(Within 71 days after the first administration.)
- Changes from baseline in potassium of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in sodium of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in chlorine of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in urine specific gravity of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in urine pH of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in urine glucose of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in urine protein of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in urine ketone body of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in urine white blood cell of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in urine bilirubin of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in urine occult blood of Laboratory Examination.(Within 71 days after the first administration.)
- Changes from baseline in Electrocardiogram.(Within 71 days after the first administration.)
- Changes from baseline in CK of Laboratory Examination(Within 71 days after the first administration.)
- Changes from baseline in CK-MB of Laboratory Examination(Within 71 days after the first administration.)
- Changes from baseline in LDH of Laboratory Examination(Within 71 days after the first administration.)
- Changes from baseline in ALP of Laboratory Examination(Within 71 days after the first administration.)
- Changes from baseline in Triglyceride of Laboratory Examination(Within 71 days after the first administration.)
- Changes from baseline in CHOL of Laboratory Examination(Within 71 days after the first administration.)
- Changes from baseline in TP of Laboratory Examination(Within 71 days after the first administration.)
- Changes from baseline in ALB of Laboratory Examination(Within 71 days after the first administration.)
- Changes from baseline in UA of Laboratory Examination(Within 71 days after the first administration.)
- Pharmacokinetics：Cmax(Within 71 days after the first administration.)
- Pharmacokinetics：AUC0-t(Within 71 days after the first administration.)
- Pharmacokinetics：AUC0-∞(Within 71 days after the first administration.)