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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
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1：40 IU/kg monoclonal antibody - Monotherapy Study | Experimental | 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). |
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| Group 2: 80 IU/kg monoclonal antibody - Monotherapy Study | Experimental | 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). |
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| Group 3: HRIG (20 IU/kg) group - Monotherapy Study | Experimental | 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). |
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| Group 4：40 IU/kg monoclonal antibody plus vaccine - Combined Administration Study | Experimental | 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). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Recombinant Human Rabies Virus Monoclonal Antibody Injection | Drug | On Day 0, administer via intramuscular injection into the lateral thigh. It is strictly prohibited to use the same syringe as the rabies vaccine or to co-administer at the same injection site. |
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of any local and systemic adverse events (AEs) within at least 30 minutes after administration of the investigational product/vaccine. | Local and systemic adverse events (AEs) | At least 30 minutes after administration |
| 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. | Local AEs, systemic AEs, and serious adverse events (SAEs) | 0-105 days |
| Vital signs changes from baseline at different observation time points following the administration of the investigational product/vaccine. | Tympanic temperature（℃） | 0-105 Days |
| Vital signs changes from baseline at different observation time points following the administration of the investigational product/vaccine. | Systolic Pressure and Diastolic Pressure (Sitting Position) （mmHg） | 0-105 Days |
| Vital signs changes from baseline at different observation time points following the administration of the investigational product/vaccine. | Pulse（bpm） | 0-105 Days |
| Changes in 12-lead electrocardiogram findings from baseline at different observation time points following administration of the investigational product/vaccine. | 12-lead electrocardiogram（Heart Rate，bpm） | 0-105 Days |
| Changes in 12-lead electrocardiogram findings from baseline at different observation time points following administration of the investigational product/vaccine. |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic Endpoints | The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 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. The following pharmacokinetic (PK) endpoints were calculated: Cmax. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jijun Chen | Contact | +86 13919275320 | chenjijun@sinopharm.com |
| Name | Affiliation | Role |
|---|---|---|
| Chaolin Huang | Wuhan Jinyintan Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lanzhou Institute of Biological Products Co., Ltd. | Lanzhou | Gansu | 730000 | China |
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| Group 5：80 IU/kg monoclonal antibody plus vaccine - Combined Administration Study | Experimental | 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). |
|
| Group 6: HRIG (20 IU/kg) plus vaccine - Combined Administration Study | Experimental | 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). |
|
| Group 7: placebo plus vaccine - Combined Administration Study | Experimental | 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). |
|
| Human Rabies Immunoglobulin (HRIG) | Drug | On Day 0, administration shall be performed via intramuscular injection into the lateral aspect of the thigh. It is strictly prohibited to use the same syringe as the rabies vaccine or to administer both agents at the same injection site. |
|
| Placebo | Drug | On Day 0, administration shall be performed via intramuscular injection into the lateral aspect of the thigh. It is strictly prohibited to use the same syringe as the rabies vaccine or to administer both agents at the same injection site. |
|
| Rabies Vaccine | Biological | On Days 0, 3, 7, 14, and 28, administer via intramuscular injection into the deltoid muscle of the upper arm. Injection into the gluteal region is prohibited. The injection on Day 0 should be administered as soon as possible after the administration of the investigational product. |
|
12-lead electrocardiogram（ Heart Rhythm） |
| 0-105 Days |
| Changes in 12-lead electrocardiogram findings from baseline at different observation time points following administration of the investigational product/vaccine. | 12-lead electrocardiogram（ST Segment，mV） | 0-105 Days |
| Changes in 12-lead electrocardiogram findings from baseline at different observation time points following administration of the investigational product/vaccine. | 12-lead electrocardiogram（Abnormal Q Wave，ms） | 0-105 Days |
| Changes in chest X-ray findings from baseline at different observation time points following administration of the investigational product/vaccine. | Chest X-ray（Cardiothoracic Ratio，>0.5） | 0-105 Days |
| Changes in chest X-ray findings from baseline at different observation time points following administration of the investigational product/vaccine. | Chest X-ray（Pulmonary Nodule Size，mm） | 0-105 Days |
| Changes in chest X-ray findings from baseline at different observation time points following administration of the investigational product/vaccine. | Chest X-ray（Costophrenic Angle，cm） | 0-105 Days |
| Changes in chest X-ray findings from baseline at different observation time points following administration of the investigational product/vaccine. | Chest X-ray（Tracheal Position，cm） | 0-105 Days |
| Changes in complete blood count (CBC) results from baseline at different observation time points following administration of the investigational product/vaccine. | White Blood Cell Count（×10⁹/L） | 0-105 Days |
| Changes in complete blood count (CBC) results from baseline at different observation time points following administration of the investigational product/vaccine. | Hemoglobin（g/L） | 0-105 Days |
| Changes in complete blood count (CBC) results from baseline at different observation time points following administration of the investigational product/vaccine. | Platelet Count（×10⁹/L） | 0-105 Days |
| Changes in complete blood count (CBC) results from baseline at different observation time points following administration of the investigational product/vaccine. | Neutrophil Percentage（%） | 0-105 Days |
| Changes in urinalysis results from baseline at different observation time points following administration of the investigational product/vaccine. | Protein（g/L） | 0-105 Days |
| Changes in urinalysis results from baseline at different observation time points following administration of the investigational product/vaccine. | Glucose（mmol/L） | 0-105 Days |
| Changes in urinalysis results from baseline at different observation time points following administration of the investigational product/vaccine. | White Blood Cells in Urine（/μL） | 0-105 Days |
| Changes in urinalysis results from baseline at different observation time points following administration of the investigational product/vaccine. | Urine Erythrocytes （/μL） | 0-105 Days |
| Changes in blood biochemistry results from baseline at different observation time points following administration of the investigational product/vaccine. | Blood Glucose （mmol/L） | 0-105 Days |
| Changes in blood biochemistry results from baseline at different observation time points following administration of the investigational product/vaccine. | Potassium （mmol/L） | 0-105 Days |
| Changes in blood biochemistry results from baseline at different observation time points following administration of the investigational product/vaccine. | Creatinine （µmol/L） | 0-105 Days |
| Changes in blood biochemistry results from baseline at different observation time points following administration of the investigational product/vaccine. | Alanine Aminotransferase（U/L） | 0-105 Days |
| Changes in blood biochemistry results from baseline at different observation time points following administration of the investigational product/vaccine. | Sodium（mmol/L） | 0-105 Days |
| Changes in blood biochemistry results from baseline at different observation time points following administration of the investigational product/vaccine. | estimated Glomerular Filtration Rate（mL/min/1.73m²） | 0-105 Days |
| Changes in routine coagulation test results from baseline at different observation time points following administration of the investigational product/vaccine. | Prothrombin Time（s） | 0-105 days |
| Pharmacodynamic Endpoints | 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. | 0-105 Days |
| Pharmacodynamic Endpoints | The geometric mean concentration (GMC) 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. | 0-105 Days |
| 105 Days |
| Pharmacokinetic Endpoints | The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 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. The following pharmacokinetic (PK) endpoints were calculated: AUC0-t. | 105 Days |
| Pharmacokinetic Endpoints | The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 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. The following pharmacokinetic (PK) endpoints were calculated: AUC0-∞. | 105 Days |
| Pharmacokinetic Endpoints | The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 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. The following pharmacokinetic (PK) endpoints were calculated: Tmax. | 105 Days |
| Pharmacokinetic Endpoints | The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 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. The following pharmacokinetic (PK) endpoints were calculated: t1/2. | 105 Days |
| Pharmacokinetic Endpoints | The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 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. The following pharmacokinetic (PK) endpoints were calculated: Vd/F. | 105 Days |
| Pharmacokinetic Endpoints | The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 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. The following pharmacokinetic (PK) endpoints were calculated: Kel. | 105 Days |
| Pharmacokinetic Endpoints | The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 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. The following pharmacokinetic (PK) endpoints were calculated: MRT. | 105 Days |
| Pharmacokinetic Endpoints | The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 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. The following pharmacokinetic (PK) endpoints were calculated: CL/F. | 105 Days |
| Anti-drug Antibodies (ADA) | The positive rate of serum anti-drug antibodies (ADA) against LZR08/LZR07 were assessed within 1 hour before the administration of the investigational product on Day 0 and at 7 days, 28 days, 56 days, 84 days, and 105 days after the administration of the investigational product/vaccine. For trial participants who tested positive for ADA, further evaluation was conducted to determine whether these were neutralizing antibodies against LZR08/LZR07. | 105 Days |
| Anti-drug Antibodies (ADA) | The titer of serum anti-drug antibodies (ADA) against LZR08/LZR07 were assessed within 1 hour before the administration of the investigational product on Day 0 and at 7 days, 28 days, 56 days, 84 days, and 105 days after the administration of the investigational product/vaccine. For trial participants who tested positive for ADA, further evaluation was conducted to determine whether these were neutralizing antibodies against LZR08/LZR07. | 105 Days |
| ID | Term |
|---|---|
| D011818 | Rabies |
| ID | Term |
|---|---|
| D018353 | Rhabdoviridae Infections |
| D018701 | Mononegavirales Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D011819 | Rabies Vaccines |
| ID | Term |
|---|---|
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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