A Phase II, Single-Center, Randomized, Blinded, Controlled Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacodynamics of a Recombinant Human Anti-Rabies Virus Monoclonal Antibody Injection in Healthy Subjects
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Occurrence of any local and systemic adverse events (AEs) within at least 30 minutes after administration of the investigational product/vaccine.
研究概览
简要总结
A Phase II, Single-Center, Randomized, Blinded, Controlled Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacodynamics of a Recombinant Human Anti-Rabies Virus Monoclonal Antibody Injection in Healthy Subjects
详细描述
Primary Objective of the study:
（1）To evaluate the safety, tolerability, and Rabies Virus Neutralizing Activity (RVNA) of different doses of a recombinant human anti-rabies virus monoclonal antibody injection (referred to as the anti-rabies mAb), administered alone or in combination with a human rabies vaccine, compared to human rabies immune globulin, in healthy adult participants aged 18-60.
Secondary Objective of the study:
- To evaluate the pharmacokinetics (PK) of the anti-rabies mAb administered alone or in combination with a human rabies vaccine in healthy adult participants aged 18-60.
- To evaluate the incidence of anti-drug antibodies for the anti-rabies mAb compared to human rabies immune globulin, administered alone or in combination with a human rabies vaccine, in healthy adult participants aged 18-60.
- To provide a basis for dose selection for Phase III clinical studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy individuals aged 18-60 years (inclusive), regardless of gender, capable of providing valid legal identification.
- •Participants voluntarily agree to participate in the study and sign an informed consent form.
- •Female participants must have no plans for pregnancy or egg donation from 14 days prior to dosing until 6 months after dosing and must voluntarily adopt effective physical contraceptive measures. Male participants must have no plans for pregnancy or sperm donation within 6 months after dosing and must voluntarily adopt effective physical contraceptive measures.
- •Female participants must weigh ≥45.0 kg and ≤80.0 kg, and male participants must weigh ≥50.0 kg and ≤80.0 kg. Body mass index (BMI) must be between 18.0 and 26.0 kg/m² (inclusive) (BMI = weight in kg / height in m²).
- •Vital signs (reference ranges: systolic blood pressure 90-140 mmHg, diastolic blood pressure 60-90 mmHg, pulse rate 50-100 beats per minute, all inclusive; body temperature assessed by the investigator according to the research center's standards), physical examination, and clinical laboratory and auxiliary tests during the screening period must be normal or judged by the investigator to have no clinical significance if abnormal.
排除标准
- •Known allergy to the investigational product (including excipients or similar drugs), or individuals with a history of severe allergic diseases or considered allergic constitution (e.g., allergies to two or more drugs, foods, or pollen) as judged by the investigator to potentially compromise participant safety.
- •Clear history of allergy to essential substances that may be encountered during the trial (e.g., skin disinfectants).
- •History of clinically severe diseases within the 6 months (180 days) prior to screening that remain unresolved, or current acute or chronic illnesses that may significantly affect the metabolism or safety evaluation of the investigational product.
- •History of autoimmune diseases or chronic hepatitis.
- •History of seizures, epilepsy, psychiatric or neurological disorders, or family history of seizures or epilepsy.
- •Major surgery within the 3 months (90 days) prior to screening, or surgery that may significantly affect the metabolism or safety evaluation of the investigational product.
- •Previous vaccination with human rabies vaccine, or suspected history of rabies exposure (defined as bites, scratches, licks on mucous membranes or broken skin by rabid, suspected rabid, or undetermined rabies status animals, or direct contact of open wounds or mucous membranes with saliva or tissues potentially containing rabies virus), as determined by inquiry.
- •Positive screening for anti-rabies virus antibodies during the screening period.
- •Vaccination with any vaccine other than the rabies vaccine within the 1 month (30 days) prior to screening.
- •Use of other antibody-based drugs or immunoglobulins within the 3 months (90 days) prior to screening.
- •Use of passive immunizing agents, immunosuppressants, or corticosteroids within the 3 months (90 days) prior to screening.
- •Use of medications that may affect the metabolism or safety evaluation of the investigational product within the 14 days prior to screening or ongoing use of such medications.
- •Participation in any clinical trial involving the use of investigational drugs or devices within the 3 months (90 days) prior to screening, or planned participation in other clinical trials during this study.
- •Regular alcohol consumption within the 3 months (90 days) prior to screening, averaging more than 2 alcohol units per day (1 unit = 17.7 mL ethanol, equivalent to 357 mL of 5% beer, 43 mL of 40% spirits, or 147 mL of 12% wine), or inability to abstain from alcohol during the trial period.
- •Smoking habit within the 3 months (90 days) prior to screening (more than 5 cigarettes or equivalent tobacco per day), or inability to abstain from smoking during the trial period.
- •Blood loss/donation exceeding 300 mL (excluding physiological blood loss in females) within the 3 months (90 days) prior to screening, receipt of blood transfusions or blood products, or plans to donate blood within 1 month (30 days) after the trial.
- •Inability to avoid strenuous exercise within 14 days after dosing.
- •History of drug abuse.
- •Pregnant or breastfeeding women.
- •History of needle or blood phobia, poor vascular condition, or intolerance to venipuncture.
- •Participants who may be unable to cooperate in completing the study for other reasons or are deemed unsuitable for inclusion by the investigator.
研究组 & 干预措施
Group 1：40 IU/kg monoclonal antibody - Monotherapy Study
60 trial participants were enrolled and randomly assigned at a 1:1:1 ratio to the 40 IU/kg monoclonal antibody group (20 participants), the HRIG control group (20 participants), and the 80 IU/kg monoclonal antibody group (20 participants).
干预措施: Recombinant Human Rabies Virus Monoclonal Antibody Injection (Drug)
Group 2: 80 IU/kg monoclonal antibody - Monotherapy Study
60 trial participants were enrolled and randomly assigned at a 1:1:1 ratio to the 40 IU/kg monoclonal antibody group (20 participants), the HRIG control group (20 participants), and the 80 IU/kg monoclonal antibody group (20 participants).
干预措施: Recombinant Human Rabies Virus Monoclonal Antibody Injection (Drug)
Group 3: HRIG (20 IU/kg) group - Monotherapy Study
60 trial participants were enrolled and randomly assigned at a 1:1:1 ratio to the 40 IU/kg monoclonal antibody group (20 participants), the HRIG control group (20 participants), and the 80 IU/kg monoclonal antibody group (20 participants).
干预措施: Human Rabies Immunoglobulin (HRIG) (Drug)
Group 4：40 IU/kg monoclonal antibody plus vaccine - Combined Administration Study
A total of 140 trial participants were enrolled and randomly assigned in a 2:2:2:1 ratio to the following groups:
40 IU/kg monoclonal antibody plus vaccine group (40 participants)
HRIG plus vaccine group (40 participants)
80 IU/kg monoclonal antibody plus vaccine group (40 participants)
Placebo plus vaccine group (20 participants).
干预措施: Recombinant Human Rabies Virus Monoclonal Antibody Injection (Drug)
Group 4：40 IU/kg monoclonal antibody plus vaccine - Combined Administration Study
A total of 140 trial participants were enrolled and randomly assigned in a 2:2:2:1 ratio to the following groups:
40 IU/kg monoclonal antibody plus vaccine group (40 participants)
HRIG plus vaccine group (40 participants)
80 IU/kg monoclonal antibody plus vaccine group (40 participants)
Placebo plus vaccine group (20 participants).
干预措施: Rabies Vaccine (Biological)
Group 5：80 IU/kg monoclonal antibody plus vaccine - Combined Administration Study
A total of 140 trial participants were enrolled and randomly assigned in a 2:2:2:1 ratio to the following groups:
40 IU/kg monoclonal antibody plus vaccine group (40 participants)
HRIG plus vaccine group (40 participants)
80 IU/kg monoclonal antibody plus vaccine group (40 participants)
Placebo plus vaccine group (20 participants).
干预措施: Recombinant Human Rabies Virus Monoclonal Antibody Injection (Drug)
Group 5：80 IU/kg monoclonal antibody plus vaccine - Combined Administration Study
A total of 140 trial participants were enrolled and randomly assigned in a 2:2:2:1 ratio to the following groups:
40 IU/kg monoclonal antibody plus vaccine group (40 participants)
HRIG plus vaccine group (40 participants)
80 IU/kg monoclonal antibody plus vaccine group (40 participants)
Placebo plus vaccine group (20 participants).
干预措施: Rabies Vaccine (Biological)
Group 6: HRIG (20 IU/kg) plus vaccine - Combined Administration Study
A total of 140 trial participants were enrolled and randomly assigned in a 2:2:2:1 ratio to the following groups:
40 IU/kg monoclonal antibody plus vaccine group (40 participants)
HRIG plus vaccine group (40 participants)
80 IU/kg monoclonal antibody plus vaccine group (40 participants)
Placebo plus vaccine group (20 participants).
干预措施: Human Rabies Immunoglobulin (HRIG) (Drug)
Group 6: HRIG (20 IU/kg) plus vaccine - Combined Administration Study
A total of 140 trial participants were enrolled and randomly assigned in a 2:2:2:1 ratio to the following groups:
40 IU/kg monoclonal antibody plus vaccine group (40 participants)
HRIG plus vaccine group (40 participants)
80 IU/kg monoclonal antibody plus vaccine group (40 participants)
Placebo plus vaccine group (20 participants).
干预措施: Rabies Vaccine (Biological)
Group 7: placebo plus vaccine - Combined Administration Study
A total of 140 trial participants were enrolled and randomly assigned in a 2:2:2:1 ratio to the following groups:
40 IU/kg monoclonal antibody plus vaccine group (40 participants)
HRIG plus vaccine group (40 participants)
80 IU/kg monoclonal antibody plus vaccine group (40 participants)
Placebo plus vaccine group (20 participants).
干预措施: Placebo (Drug)
Group 7: placebo plus vaccine - Combined Administration Study
A total of 140 trial participants were enrolled and randomly assigned in a 2:2:2:1 ratio to the following groups:
40 IU/kg monoclonal antibody plus vaccine group (40 participants)
HRIG plus vaccine group (40 participants)
80 IU/kg monoclonal antibody plus vaccine group (40 participants)
Placebo plus vaccine group (20 participants).
干预措施: Rabies Vaccine (Biological)
结局指标
主要结局
Occurrence of any local and systemic adverse events (AEs) within at least 30 minutes after administration of the investigational product/vaccine.
时间窗: At least 30 minutes after administration
Local and systemic adverse events (AEs)
Occurrence of any local AEs, systemic AEs, and serious adverse events (SAEs) from the administration of the investigational product on Day 0 until the last visit.
时间窗: 0-105 days
Local AEs, systemic AEs, and serious adverse events (SAEs)
Vital signs changes from baseline at different observation time points following the administration of the investigational product/vaccine.
时间窗: 0-105 Days
Tympanic temperature（℃）
Changes in 12-lead electrocardiogram findings from baseline at different observation time points following administration of the investigational product/vaccine.
时间窗: 0-105 Days
12-lead electrocardiogram（Heart Rate，bpm）
Changes in chest X-ray findings from baseline at different observation time points following administration of the investigational product/vaccine.
时间窗: 0-105 Days
Chest X-ray（Cardiothoracic Ratio，\>0.5）
Changes in complete blood count (CBC) results from baseline at different observation time points following administration of the investigational product/vaccine.
时间窗: 0-105 Days
White Blood Cell Count（×10⁹/L）
Changes in urinalysis results from baseline at different observation time points following administration of the investigational product/vaccine.
时间窗: 0-105 Days
Protein（g/L）
Changes in blood biochemistry results from baseline at different observation time points following administration of the investigational product/vaccine.
时间窗: 0-105 Days
Blood Glucose （mmol/L）
Changes in routine coagulation test results from baseline at different observation time points following administration of the investigational product/vaccine.
时间窗: 0-105 days
Prothrombin Time（s）
Pharmacodynamic Endpoints
时间窗: 0-105 Days
The positive rate (with a positivity threshold of RVNA ≥ 0.5 IU/mL) of serum rabies virus neutralizing antibodies (RVNA) were measured at the following time points: within 1 hour before the administration of the investigational product on Day 0, and at 4 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 5 days, 7 days, 10 days, 14 days, 28 days, 42 days, 56 days, 84 days, and 105 days after the administration of the investigational product/vaccine.
次要结局
- Pharmacokinetic Endpoints(105 Days)
- Anti-drug Antibodies (ADA)(105 Days)