Study to Evaluate GR1801's Efficacy and Safety

NCT05846568 | Completed Phase 3 DMC

• 1 other identifier: GR1801-003
• Study Type: interventional
• Target: 1,200
• Locations: 1 country
• Sites: 1

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.

Conditions

Rabies Post-exposure Prophylaxis

Keywords

Rabies; Rabies virus neutralizing antibodies; Post-exposure prophylaxis

Outcome Measures

Primary Outcomes (3)

• 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.

  7 days

• 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.

  14 days

• 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.

  365 days

Secondary Outcomes (10)

• To evaluate the rabies post-exposure morbidity of GR1801 compared to HRIG within 90 days and 365 days after administration.

  365 days

• To evaluate the rabies post-exposure mortality of GR1801 compared to HRIG within 90 days and 365 days after administration.

  365 days

• To evaluate the rabies post-exposure survival rate of GR1801 compared to HRIG within 90 days and 365 days after administration.

  365 days

• To evaluate the Geometric mean RVNA Concentration of GR1801 compared to HRIG within 1,3,5,14,42,90 and 365 days after administration.

  365 days

• 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.

  365 days

Study Arms (2)

Experimental Group: GR1801+Rabies vaccine(CHENGDA PHARMACEUTICALS)

EXPERIMENTAL

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.

Biological: GR1801; Biological: Rabies Vaccine

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

ACTIVE COMPARATOR

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.

Biological: Human Rabies Immunoglobulin(HRIG); Biological: Rabies Vaccine

Interventions

GR1801 BIOLOGICAL

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.

Experimental Group: GR1801+Rabies vaccine(CHENGDA PHARMACEUTICALS)

Human Rabies Immunoglobulin(HRIG) BIOLOGICAL

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.

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

Rabies Vaccine BIOLOGICAL

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) .

Control Group:HRIG（BOYA-BIO）+Rabies vaccine(CHENGDA PHARMACEUTICALS); Experimental Group: GR1801+Rabies vaccine(CHENGDA PHARMACEUTICALS)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genrix (Shanghai) Biopharmaceutical Co., Ltd.: lead

Study Sites (1)

Center for Disease Control and Prevention (CDC)

Kunming, Yunnan, 650000, China

Location

MeSH Terms

Conditions

Rabies

Interventions

Rabies Vaccines

Condition Hierarchy (Ancestors)

Rhabdoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Xiaoqiang Liu, PHD

  Yunnan Province Center for Disease Control and Prevention (CDC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double blind
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: April 6, 2023
• First Posted: May 6, 2023
• Study Start: October 21, 2022
• Primary Completion: September 6, 2023
• Study Completion: September 6, 2024
• Last Updated: September 25, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)