Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity of GR2001 in Chinese Healthy Adults

Phase 1

Completed

• Conditions: Tetanus
• Interventions: Biological: GR2001; Biological: Placebo; Biological: HTIG; Biological: Tetanus Toxoid

• Registration Number: NCT06302374
• Lead Sponsor: Genrix (Shanghai) Biopharmaceutical Co., Ltd.

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2023-03-04
• Primary Completion: 2023-11-01
• Study Completion: 2024-02-19
• Study First Submitted: 2024-02-28
• Status Verified: 2024-03
• Study First Submitted QC: 2024-03-04
• Last Update Submitted: 2024-03-04
• Study First Posted: 2024-03-08
• Last Update Posted: 2024-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 202

Inclusion Criteria

1. Healthy male or female, 18-60 years of age (both inclusive);
2. Body mass index within 18.0-27.0 kg/m2 (both inclusive);
3. Subjects including partners are willing to voluntarily take effective contraceptive measures from screening to 6 months after the last study drug administration.
4. Completed written informed consent process, signed the informed consent forms and Agreed to complete all follow-ups.

Exclusion Criteria

1. History or evidence of severe drug or excipient allergy;
2. History or evidence of tetanus infection;
3. Inoculation of tetanus vaccine within 10 years;
4. History or evidence of any other acute or chronic disease；
5. Known or suspected history of drug abuse；
6. Positive outcome for Tetanus-antibody IgG test;
7. Nursing mothers or pregnant women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 4 GR2001 0.1mg/kg/placebo	Placebo	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 6 GR2001 0.1mg/kg/placebo	GR2001	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 1 GR2001 0.01mg/kg/placebo	Placebo	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	Placebo	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	HTIG	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 6 GR2001 0.1mg/kg/placebo	Placebo	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 4 GR2001 0.1mg/kg/placebo	GR2001	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	GR2001	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	Placebo	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 7 GR2001 0.2mg/kg/placebo	GR2001	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 2 GR2001 0.02mg/kg/placebo	GR2001	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	GR2001	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 7 GR2001 0.2mg/kg/placebo	Placebo	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 1 GR2001 0.01mg/kg/placebo	GR2001	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 5 GR2001 0.2mg/kg/placebo	Placebo	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 6 GR2001 0.1mg/kg/placebo	Tetanus Toxoid	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	Tetanus Toxoid	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	HTIG	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.
Cohort 8 GR2001 0.1mg/kg/ GR2001 0.2mg/kg/ HTIG	GR2001	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.
Cohort 8 GR2001 0.1mg/kg/ GR2001 0.2mg/kg/ HTIG	Tetanus Toxoid	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.

Primary Outcome Measures

Name	Time	Method
Incidence of AEs(Phase I)	Up to 105 days	Number of participants with treatment-related adverse events or serious adverse events.
Tetanus-antibody titer(Phase II)	24 hours post administration	Tetanus-antibody titer post administration.

Secondary Outcome Measures

Name	Time	Method
Mean Residence Time (MRT)	Up to 105 days	Estimated by non-compartmental analysis (NCA) with WinNonlin.
Incidence of ADA(Phase I/II)	Up to 105 days	Incidence of ADA post administration.
Incidence of AEs(Phase II)	Up to 105 days	Number of participants with treatment-related adverse events or serious adverse events.
Peak plasma concentration(Cmax)	Up to 105 days	Estimated by non-compartmental analysis (NCA) with WinNonlin.
Area under the plasma concentration versus time curve (AUC)	Up to 105 days	Estimated by non-compartmental analysis (NCA) with WinNonlin.
Apparent total body clearance (CL/F)	Up to 105 days	Estimated by non-compartmental analysis (NCA) with WinNonlin.
Tetanus-antibody titer(Phase I/II)	Up to 105 days	Tetanus-antibody titer post administration.
Time of maximum plasma concentration (Tmax)	Up to 105 days	Estimated by non-compartmental analysis (NCA) with WinNonlin.
Apparent volume of distribution (Vd/F)	Up to 105 days	Estimated by non-compartmental analysis (NCA) with WinNonlin.
The elimination rate constant (Kel)	Up to 105 days	Estimated by non-compartmental analysis (NCA) with WinNonlin.
Terminal half-life (T1/2)	Up to 105 days	Estimated by non-compartmental analysis (NCA) with WinNonlin.

Trial Locations

Locations (1)

Huashan Hospital affiliated of Fudan University; 🇨🇳 Shanghai, Shanghai, China