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

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

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.

Study Overview

• Status: Completed
• Conditions: Tetanus
• Intervention / Treatment: Biological: Placebo; Biological: GR2001; Biological: HTIG; Biological: Tetanus Toxoid

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 Type: Interventional
• Enrollment (Actual): 202
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Huashan Hospital affiliated of Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 GR2001 0.01mg/kg/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).	Biological: Placebo; intramuscular injection; Biological: GR2001; intramuscular injection
Experimental: Cohort 2 GR2001 0.02mg/kg/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).	Biological: Placebo; intramuscular injection; Biological: GR2001; intramuscular injection
Experimental: Cohort 3 GR2001 0.05mg/kg/placebo/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).	Biological: Placebo; intramuscular injection; Biological: GR2001; intramuscular injection; Biological: HTIG; intramuscular injection
Experimental: Cohort 4 GR2001 0.1mg/kg/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).	Biological: Placebo; intramuscular injection; Biological: GR2001; intramuscular injection
Experimental: Cohort 5 GR2001 0.2mg/kg/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).	Biological: Placebo; intramuscular injection; Biological: GR2001; intramuscular injection
Experimental: Cohort 6 GR2001 0.1mg/kg/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.	Biological: Placebo; intramuscular injection; Biological: GR2001; intramuscular injection; Biological: Tetanus Toxoid; intramuscular injection
Experimental: Cohort 7 GR2001 0.2mg/kg/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.	Biological: Placebo; intramuscular injection; Biological: GR2001; intramuscular injection; Biological: Tetanus Toxoid; intramuscular injection
Experimental: Cohort 8 GR2001 0.1mg/kg/ GR2001 0.2mg/kg/ 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.	Biological: GR2001; intramuscular injection; Biological: HTIG; intramuscular injection; Biological: Tetanus Toxoid; intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Genrix (Shanghai) Biopharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Jing Zhang, PHD, Huashan Hospital affiliated of Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2023
• Primary Completion (Actual): November 1, 2023
• Study Completion (Actual): February 19, 2024

Study Registration Dates

• First Submitted: February 28, 2024
• First Submitted That Met QC Criteria: March 4, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Clostridium Infections; Tetanus
• Other Study ID Numbers: GR2001-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No