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Study to Evaluate GR1801's Efficacy and Safety

Primary Purpose

Rabies Post-exposure Prophylaxis

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
GR1801
Human Rabies Immunoglobulin(HRIG)
Rabies Vaccine
Sponsored by
Genrix (Shanghai) Biopharmaceutical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Rabies Post-exposure Prophylaxis focused on measuring Rabies, Rabies virus neutralizing antibodies, Post-exposure prophylaxis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Chinese males or females aged 18 years or above on Study Day 0 with legal identification documents and plan to live in the local area during the study; WHO Category III rabies exposure; Those who have an armpit temperature ≤ 37.0 °C; Completed written informed consent process, signed the informed consent forms and Agreed to complete all follow-ups. Exclusion Criteria: WHO Category III rabies exposure but received wound suture treatment; WHO Category III rabies exposure over 72 hours; Previous receipt of rabies vaccination or rabies passive immunization; History of bitten by animals such as dogs, cats, bats etc. within the 6 months before the Study Day 0; History of any severe allergy for vaccination; Had fever (armpit temperature ≥ 38.5 °C) or received any antipyretic, analgesic or anti-allergic drug within 3 days before Study Day 0; History of severe autoimmune diseases; History of any severe neurological disease; History of receiving any immunoglobulin or vaccine within 30 days before Study Day 0, or plan to use any such product during the study; History of addiction to any narcotic, alcohol or drugs; Previous receipt of any study product (drug, vaccine, biological product or device) within 6 months before Study Day 0, or plan to participate in any other clinical study during this study period; Females who are pregnant or with urine pregnancy test positive.

Sites / Locations

  • Center for Disease Control and Prevention (CDC)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Experimental Group: GR1801+Rabies vaccine(CHENGDA PHARMACEUTICALS)

Control Group:HRIG(BOYA-BIO)+Rabies vaccine(CHENGDA PHARMACEUTICALS)

Arm Description

GR1801 injections are administered by wound infiltration injection or by intramuscular injection.GR1801 injections are a bispecific monoclonal antibody that exhibit a wide spectrum of activity against various wild-type rabies strains in vitro. Dosage form:2mg/1mL/vial, liquid, Dosage: 0.05mg/kg of GR1801 Frequency/duration: at Day 0. Rabies vaccine should be administered in deltoid muscle Dosage form: >=2.5 IU, freeze-dried vaccine, 0.5 mL after reconstitution, Frequency/duration: at Day 0, 3, 7, 14, 28.

HRIG is administered by wound infiltration injection or by intramuscular injection. Dosage form: 200 IU/2mL/vial, liquid, Dosage: 20 IU/kg, Frequency/duration: at Day 0. Rabies vaccine should be administered in deltoid muscle Dosage form: >=2.5 IU, freeze-dried vaccine, 0.5 mL after reconstitution, Frequency/duration: at Day 0, 3, 7, 14, 28.

Outcomes

Primary Outcome Measures

To evaluate the Geometric mean RVNA Concentration (accessd by Rapid Fluorescent Foci Inhibition Test(RIFFIT)) for GR1801 recipients is non-inferior to the Geometric mean RVNA Concentration for HRIG recipients on Study Day 7.
RVNA(Rabies Virus Neutralizing Antibodies) geometric mean concentration of GR1801 recipients and HRIG recipients in combination with rabies vaccines.
To evaluate the percentage of subjects with RVNA concentration ≥ 0.5 IU/mL on Study Day 14 in GR1801 recipients is non-inferior to the percentage of subjects with RVNA concentration ≥ 0.5 IU/mL for HRIG.
The percentage of subjects with the RVNA geometric mean concentration ≥ 0.5 IU/mL in GR1801 recipients and HRIG recipients in combination with rabies vaccines.
To evaluate the rabies post-exposure protection rate for GR1801 recipients is non-inferior to the protection rate for HRIG recipients on Study Day 365.
The percentage of subjects with no case of rabies death in GR1801 recipients and HRIG recipients in combination with rabies vaccines.

Secondary Outcome Measures

To evaluate the rabies post-exposure morbidity of GR1801 compared to HRIG within 90 days and 365 days after administration.
The percentage of subjects with probable or confirmed cases of rabies.
To evaluate the rabies post-exposure mortality of GR1801 compared to HRIG within 90 days and 365 days after administration.
The percentage of subjects with cases of rabies death.
To evaluate the rabies post-exposure survival rate of GR1801 compared to HRIG within 90 days and 365 days after administration.
The percentage of subjects with rabies-free survival.
To evaluate the Geometric mean RVNA Concentration of GR1801 compared to HRIG within 1,3,5,14,42,90 and 365 days after administration.
RVNA geometric mean concentration.
To evaluate the percentage of subjects with RVNA concentration ≥ 0.5 IU/mL of GR1801 compared to HRIG within 1,3,5,7,42,90 and 365 days after administration.
The percentage of subjects with RVNA geometric mean concentration ≥ 0.5 IU/mL.
To evaluate the detection rate of RVNA concentration of GR1801 compared to HRIG within 1,3,5,7,14,42,90 and 365 days after administration.
The percentage of subjects whose RVNA geometric mean concentration are below the quantization limit.
To evaluate the safety of GR1801 compared to HRIG within 365 days.
Number of participants with treatment-related adverse events or serious adverse events as assessed by CTCAE v5.0
To evaluate the peak plasma concentration(Cmax) of GR1801 within 365 days.
The peak plasma concentration of GR1801 will be estimated at D3,D7,D14 and D42,using non compartmental analysis.
To evaluate the Area under the plasma concentration versus time curve (AUC0-last,AUC0-inf) of GR1801 within 365 days.
The Area under the plasma concentration versus time curve (AUC0-last,AUC0-inf) of GR1801 will be estimated at D3,D7,D14 and D42,using non compartmental analysis.
To evaluate the immunogenicity of GR1801 within 365 days.
To assess the anti-drug-antibodies (ADA) and neutralizing antibodies (NAb) of GR1801.

Full Information

First Posted
April 6, 2023
Last Updated
September 17, 2023
Sponsor
Genrix (Shanghai) Biopharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05846568
Brief Title
Study to Evaluate GR1801's Efficacy and Safety
Official Title
A Phase III Clinical Trail to Evaluate the Efficacy,Safety,Pharmacokinetics and Immunogenicity Characteristics of GR1801 Injection for the Post-exposure Prophylaxis (PEP) of WHO Category 3 Rabies Exposure Patients.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 21, 2022 (Actual)
Primary Completion Date
September 6, 2023 (Actual)
Study Completion Date
July 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genrix (Shanghai) Biopharmaceutical Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The goal of this clinical trial is to compare the efficacy and safety of GR1801 injection with Human Rabies Immunoglobulin(HRIG) in patients with WHO Category 3 rabies exposure. Patients will receive GR1801 injection or HRIG. Each group will receive rabies vaccine as the WHO Essen regime after Study Drug.
Detailed Description
This is a randomized, double-blind, Human Rabies Immunoglobulin(HRIG) controlled Phase III clinical trial evaluating the efficacy, safety, pharmacokinetic and immunogenicity of GR1801 injection as a part of post-exposure prophylaxis (PEP) in patients with WHO Category 3 rabies exposure who have met all inclusion/exclusion criteria for their treatment group. 1200 patients aged 18 and above with WHO Category III rabies exposure should be enrolled as planned and randomly assigned to the experimental group and the control group based on a ratio of 3: 1. The random stratification factors include time of exposure (within or beyond 24 hours), bite location (above or below the neck), and number of bites (1 or more). All the patients should receive wound infiltration injection of GR1801 or HRIG on Study Day 0 (wound conditions should be described and recorded both before and post injection by photos, including diameter, depth, expansion treatment, etc.), and should also receive intramuscular injection of one dose of the freeze-dried rabies vaccine for human use (Vero cells) into the deltoid muscle after the infiltration injection. Patients should also be given one dose of the freeze-dried rabies vaccine for human use (Vero cells) on Study Days 3, 7, 14, and 28 respectively according to the WHO Essen regime. Rabies virus neutralizing antibodies (RVNA) should be collected 9 times from each subject prior to administration and on Study Day1, 3, 5, 7, 14, 42, 90, 365 post administration of Study Drug. RVNA should be assayed through rapid fluorescence focus inhibition test (RFFIT). The occurrence of rabies and survival conditions should be collected through every follow-up visit. Adverse events should be classified in accordance with solicited adverse events and unsolicited adverse events. Solicited adverse events include local adverse events (such as injection sites pain, induration, swelling, redness, rash and pruritus) and systemic adverse events (such as fever, hypersensitivity, headache, fatigue, nausea, vomiting, arthralgia and myalgia). Unsolicited adverse events are those except solicited adverse events or solicited adverse events beyond 7 days after the first administration. Solicited adverse events should be collected 7 days after the first administration. Unsolicited adverse events should be collected in 3 months after the first administration and serious adverse events(SAE) should be collected throughout the trial.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rabies Post-exposure Prophylaxis
Keywords
Rabies, Rabies virus neutralizing antibodies, Post-exposure prophylaxis

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
1200 patients aged 18 and above with WHO Category III rabies exposure should be enrolled as planned and randomly assigned to the GR1801 injection group and the HRIG group based on a ratio of 3: 1. The random stratification factors include time of exposure (within or beyond 24 hours), bite location (above or below the neck), and number of bites (1 or more).
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
double blind
Allocation
Randomized
Enrollment
1200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental Group: GR1801+Rabies vaccine(CHENGDA PHARMACEUTICALS)
Arm Type
Experimental
Arm Description
GR1801 injections are administered by wound infiltration injection or by intramuscular injection.GR1801 injections are a bispecific monoclonal antibody that exhibit a wide spectrum of activity against various wild-type rabies strains in vitro. Dosage form:2mg/1mL/vial, liquid, Dosage: 0.05mg/kg of GR1801 Frequency/duration: at Day 0. Rabies vaccine should be administered in deltoid muscle Dosage form: >=2.5 IU, freeze-dried vaccine, 0.5 mL after reconstitution, Frequency/duration: at Day 0, 3, 7, 14, 28.
Arm Title
Control Group:HRIG(BOYA-BIO)+Rabies vaccine(CHENGDA PHARMACEUTICALS)
Arm Type
Active Comparator
Arm Description
HRIG is administered by wound infiltration injection or by intramuscular injection. Dosage form: 200 IU/2mL/vial, liquid, Dosage: 20 IU/kg, Frequency/duration: at Day 0. Rabies vaccine should be administered in deltoid muscle Dosage form: >=2.5 IU, freeze-dried vaccine, 0.5 mL after reconstitution, Frequency/duration: at Day 0, 3, 7, 14, 28.
Intervention Type
Biological
Intervention Name(s)
GR1801
Intervention Description
The injection solution GR1801 does not contain preservatives. The excipients include histidine/histidine hydrochloride (20mM), trehalose (90 mg/mL), disodium EDTA (0.372mg/mL) and polysorbate 80 (0.5 mg/mL). The pH value is 5.8 and each bottle contains 2mg of GR1801 protein. The packaging material is a borosilicate glass tube injection bottle (2mL) with a halogenated butyl rubber stopper for injection and an aluminum-plastic composite cap for antibiotic bottles.
Intervention Type
Biological
Intervention Name(s)
Human Rabies Immunoglobulin(HRIG)
Intervention Description
The HRIG is a Chinese licensed Human Rabies Immunoglobulin produced by BOYA-BIO, which are derived from human plasma, and then purified and filled in the injectable vial form.
Intervention Type
Biological
Intervention Name(s)
Rabies Vaccine
Intervention Description
The Chinese licensed freeze-dried rabies vaccine produced by CHENGDA PHARMACEUTICALS for human use (Vero Cells) which is indicated for the rabies Post-exposure Prophylaxis (PEP) .
Primary Outcome Measure Information:
Title
To evaluate the Geometric mean RVNA Concentration (accessd by Rapid Fluorescent Foci Inhibition Test(RIFFIT)) for GR1801 recipients is non-inferior to the Geometric mean RVNA Concentration for HRIG recipients on Study Day 7.
Description
RVNA(Rabies Virus Neutralizing Antibodies) geometric mean concentration of GR1801 recipients and HRIG recipients in combination with rabies vaccines.
Time Frame
7 days
Title
To evaluate the percentage of subjects with RVNA concentration ≥ 0.5 IU/mL on Study Day 14 in GR1801 recipients is non-inferior to the percentage of subjects with RVNA concentration ≥ 0.5 IU/mL for HRIG.
Description
The percentage of subjects with the RVNA geometric mean concentration ≥ 0.5 IU/mL in GR1801 recipients and HRIG recipients in combination with rabies vaccines.
Time Frame
14 days
Title
To evaluate the rabies post-exposure protection rate for GR1801 recipients is non-inferior to the protection rate for HRIG recipients on Study Day 365.
Description
The percentage of subjects with no case of rabies death in GR1801 recipients and HRIG recipients in combination with rabies vaccines.
Time Frame
365 days
Secondary Outcome Measure Information:
Title
To evaluate the rabies post-exposure morbidity of GR1801 compared to HRIG within 90 days and 365 days after administration.
Description
The percentage of subjects with probable or confirmed cases of rabies.
Time Frame
365 days
Title
To evaluate the rabies post-exposure mortality of GR1801 compared to HRIG within 90 days and 365 days after administration.
Description
The percentage of subjects with cases of rabies death.
Time Frame
365 days
Title
To evaluate the rabies post-exposure survival rate of GR1801 compared to HRIG within 90 days and 365 days after administration.
Description
The percentage of subjects with rabies-free survival.
Time Frame
365 days
Title
To evaluate the Geometric mean RVNA Concentration of GR1801 compared to HRIG within 1,3,5,14,42,90 and 365 days after administration.
Description
RVNA geometric mean concentration.
Time Frame
365 days
Title
To evaluate the percentage of subjects with RVNA concentration ≥ 0.5 IU/mL of GR1801 compared to HRIG within 1,3,5,7,42,90 and 365 days after administration.
Description
The percentage of subjects with RVNA geometric mean concentration ≥ 0.5 IU/mL.
Time Frame
365 days
Title
To evaluate the detection rate of RVNA concentration of GR1801 compared to HRIG within 1,3,5,7,14,42,90 and 365 days after administration.
Description
The percentage of subjects whose RVNA geometric mean concentration are below the quantization limit.
Time Frame
365 days
Title
To evaluate the safety of GR1801 compared to HRIG within 365 days.
Description
Number of participants with treatment-related adverse events or serious adverse events as assessed by CTCAE v5.0
Time Frame
365 days
Title
To evaluate the peak plasma concentration(Cmax) of GR1801 within 365 days.
Description
The peak plasma concentration of GR1801 will be estimated at D3,D7,D14 and D42,using non compartmental analysis.
Time Frame
365 days
Title
To evaluate the Area under the plasma concentration versus time curve (AUC0-last,AUC0-inf) of GR1801 within 365 days.
Description
The Area under the plasma concentration versus time curve (AUC0-last,AUC0-inf) of GR1801 will be estimated at D3,D7,D14 and D42,using non compartmental analysis.
Time Frame
365 days
Title
To evaluate the immunogenicity of GR1801 within 365 days.
Description
To assess the anti-drug-antibodies (ADA) and neutralizing antibodies (NAb) of GR1801.
Time Frame
365 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Chinese males or females aged 18 years or above on Study Day 0 with legal identification documents and plan to live in the local area during the study; WHO Category III rabies exposure; Those who have an armpit temperature ≤ 37.0 °C; Completed written informed consent process, signed the informed consent forms and Agreed to complete all follow-ups. Exclusion Criteria: WHO Category III rabies exposure but received wound suture treatment; WHO Category III rabies exposure over 72 hours; Previous receipt of rabies vaccination or rabies passive immunization; History of bitten by animals such as dogs, cats, bats etc. within the 6 months before the Study Day 0; History of any severe allergy for vaccination; Had fever (armpit temperature ≥ 38.5 °C) or received any antipyretic, analgesic or anti-allergic drug within 3 days before Study Day 0; History of severe autoimmune diseases; History of any severe neurological disease; History of receiving any immunoglobulin or vaccine within 30 days before Study Day 0, or plan to use any such product during the study; History of addiction to any narcotic, alcohol or drugs; Previous receipt of any study product (drug, vaccine, biological product or device) within 6 months before Study Day 0, or plan to participate in any other clinical study during this study period; Females who are pregnant or with urine pregnancy test positive.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaoqiang Liu, PHD
Phone
0871-63627796
Email
lxq7611@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaoqiang Liu, PHD
Organizational Affiliation
Yunnan Province Center for Disease Control and Prevention (CDC)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Disease Control and Prevention (CDC)
City
Kunming
State/Province
Yunnan
ZIP/Postal Code
650000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaoqiang Liu, PHD
Phone
0871-63627796
Email
lxq7611@126.com
First Name & Middle Initial & Last Name & Degree
Xiaoqiang Liu, PHD

12. IPD Sharing Statement

Learn more about this trial

Study to Evaluate GR1801's Efficacy and Safety

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