Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and Immunogenicity characteristics of GR2001 and compare the anti-tetanus neutralizing antibody titers of GR2001 with human tetanus immunoglobulin (HTIG)in healthy adult subjects.
This is a Multicentre, Randomized, Double-Blind, Placebo-Controlled, Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity of GR2001 Injection in Healthy Subjects.
In the phase I part of the study, a total of 94 healthy subjects will be enrolled. The 94 healthy adult subjects will be enrolled into 7 cohorts sequentially. Each participant will receive a single IM dose of GR2001 or placebo or HTIG according to the cohort in which they were enrolled. After injection (Day 0), participants will remain in the study site for observation up to Day 1. The phase I part will last for 105 days following the assessments of safety, PK, PD and ADA.
In the phase II part of the study, a total of 108 healthy subjects will be enrolled. The 108 healthy subjects will be randomly assigned to the experimental group and the control group based on a ratio of 1:1:1:2:2:2.The phase II part will last for 105 days following the assessments of safety, PK, PD and ADA.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 GR2001 0.01mg/kg/placebo | Experimental | Four subjects will be randomly assigned to receive either GR2001 or placebo at a 3:1 ratio (i.e. 3 subjects receive GR2001 and 1 with placebo). |
|
| Cohort 2 GR2001 0.02mg/kg/placebo | Experimental | Ten subjects will be randomly assigned to receive either GR2001 or placebo at a 4:1 ratio (i.e. 8 subjects receive GR2001 and 2 with placebo). |
|
| Cohort 3 GR2001 0.05mg/kg/placebo/HTIG | Experimental | 24 subjects will be randomly assigned to receive GR2001 or placebo or HTIG(250IU) at a 1:1:1 ratio (i.e. 8 subjects receive GR2001, 8 with placebo and 8 with HTIG). |
|
| Cohort 4 GR2001 0.1mg/kg/placebo | Experimental | Ten subjects will be randomly assigned to receive either GR2001 or placebo at a 4:1 ratio (i.e. 8 subjects receive GR2001 and 2 with placebo). |
|
| Cohort 5 GR2001 0.2mg/kg/placebo | Experimental | Ten subjects will be randomly assigned to receive either GR2001 or placebo at a 4:1 ratio (i.e. 8 subjects receive GR2001 and 2 with placebo). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GR2001 | Biological | intramuscular injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of AEs(Phase I) | Number of participants with treatment-related adverse events or serious adverse events. | Up to 105 days |
| Tetanus-antibody titer(Phase II) | Tetanus-antibody titer post administration. | 24 hours post administration |
| Measure | Description | Time Frame |
|---|---|---|
| Tetanus-antibody titer(Phase I/II) | Tetanus-antibody titer post administration. | Up to 105 days |
| Incidence of ADA(Phase I/II) | Incidence of ADA post administration. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Jing Zhang, PHD | Huashan Hospital affiliated of Fudan University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Huashan Hospital affiliated of Fudan University | Shanghai | Shanghai Municipality | 200040 | China |
Not provided
| ID | Term |
|---|---|
| D013742 | Tetanus |
| ID | Term |
|---|---|
| D003015 | Clostridium Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
Not provided
Not provided
| ID | Term |
|---|---|
| D013745 | Tetanus Toxoid |
| ID | Term |
|---|---|
| D014121 | Toxoids |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
Not provided
Not provided
In the phase I part of the study, a total of 94 healthy subjects will be enrolled. The 94 healthy adult subjects will be enrolled into 7 cohorts sequentially. Each participant will receive a single IM dose of GR2001 or placebo or HTIG according to the cohort in which they were enrolled. After injection (Day 0), participants will remain in the study site for observation up to Day 1. The phase I part will last for 105 days following the assessments of safety, PK, PD and ADA.
In the phase II part of the study, a total of 108 healthy subjects will be enrolled. The 108 healthy subjects will be randomly assigned to the experimental group and the control group based on a ratio of 1:1:1:2:2:2.The phase II part will last for 105 days following the assessments of safety, PK, PD and ADA.
Not provided
Not provided
Double Blind
|
| Cohort 6 GR2001 0.1mg/kg/placebo | Experimental | Eighteen subjects will be randomly assigned to receive either GR2001 or placebo at a 2:1 ratio (i.e. 12 subjects receive GR2001 and 6 with placebo) followed by a dose of Tetanus Toxoid（TT） on Day0. |
|
| Cohort 7 GR2001 0.2mg/kg/placebo | Experimental | Eighteen subjects will be randomly assigned to receive either GR2001 or placebo at a 2:1 ratio (i.e. 12 subjects receive GR2001 and 6 with placebo) followed by a dose of Tetanus Toxoid（TT） on Day0. |
|
| Cohort 8 GR2001 0.1mg/kg/ GR2001 0.2mg/kg/ HTIG | Experimental | Thirty six subjects will be randomly assigned to receive GR2001(0.1mg/kg) or GR2001(0.2mg/kg) or HTIG(250IU) at a 1:1:1 ratio (i.e. 12 subjects receive GR2001(0.1mg/kg), 12 with GR2001(0.2mg/kg) and 12 with HTIG). Seventy two subjects will be randomly assigned to receive GR2001(0.1mg/kg) or GR2001(0.2mg/kg) or HTIG(250IU) at a 1:1:1 ratio (i.e. 24 subjects receive GR2001(0.1mg/kg), 24 with GR2001(0.2mg/kg) and 24 with HTIG) followed by one dose of Tetanus Toxoid（TT） on Day0 and Day28. |
|
| Placebo | Biological | intramuscular injection |
|
| HTIG | Biological | intramuscular injection |
|
| Tetanus Toxoid | Biological | intramuscular injection |
|
| Up to 105 days |
| Incidence of AEs(Phase II) | Number of participants with treatment-related adverse events or serious adverse events. | Up to 105 days |
| Peak plasma concentration(Cmax) | Estimated by non-compartmental analysis (NCA) with WinNonlin. | Up to 105 days |
| Area under the plasma concentration versus time curve (AUC) | Estimated by non-compartmental analysis (NCA) with WinNonlin. | Up to 105 days |
| Time of maximum plasma concentration (Tmax) | Estimated by non-compartmental analysis (NCA) with WinNonlin. | Up to 105 days |
| Terminal half-life (T1/2) | Estimated by non-compartmental analysis (NCA) with WinNonlin. | Up to 105 days |
| Apparent total body clearance (CL/F) | Estimated by non-compartmental analysis (NCA) with WinNonlin. | Up to 105 days |
| Apparent volume of distribution (Vd/F) | Estimated by non-compartmental analysis (NCA) with WinNonlin. | Up to 105 days |
| The elimination rate constant (Kel) | Estimated by non-compartmental analysis (NCA) with WinNonlin. | Up to 105 days |
| Mean Residence Time (MRT) | Estimated by non-compartmental analysis (NCA) with WinNonlin. | Up to 105 days |
| D007239 | Infections |