A Phase III Clinical Study to Evaluate SYN023's Efficacy and Safety

NCT04644484 | Completed Phase 3 Results FDA Drug

• 1 other identifier: SYN023-006
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 3, blinded, randomized study of SYN023 compared to a China licensed Human Rabies Immunoglobulin (a Rabies immune globulin from human sources, HRIG) for the prevention of rabies as part of post-exposure prophylaxis (PEP). The trial will enroll the World Health Organization (WHO) Category III rabies exposure subjects. The subject's death and rabies data will be reviewed by Data and safety monitoring board (DSMB) to confirm the safety. Besides, rabies vaccine would be administered after Study Drug in each group. This trial is proposed to further the licensure of SYN023 to provide an effective PEP alternative available to those exposed persons who need such a product. A placebo-controlled rabies trial is unethical thus HRIG is selected as the control group. Rabies immune globulin from equine and human sources (HRIG) have been evaluated in many trials and HRIG is the standard of care in China.

Conditions

Rabies; Communicable Disease; Virus Diseases; Rhabdoviridae Infections; Mononegavirales Infections; RNA Virus Infections

Keywords

Post-exposure prophylaxis of Rabies

Outcome Measures

Primary Outcomes (2)

• Rabies Virus Neutralizing Activity (RVNA) of Geometric Mean Concentration (GMC) at Study Day 8

  Rabies Virus Neutralizing Activity (RVNA) was assessed using Rapid Fluorescent Focus Inhibition Test (RFFIT).

  Day 8

• Number of Probable or Confirmed Rabies Cases

  WHO's Classification of Rabies Cases: 1. Suspected case: refers to a case that satisfies the definition of clinical case; 2. Probable case: refers to a suspected case with a reliable medical history of contact with any suspected animal infected with the rabies virus; 3. Confirmed case: refers to a suspected or probable case that is proved to be infected based on the lab test result.

  Day 1 to Day 365

Secondary Outcomes (3)

• Rabies Virus Neutralizing Activity (RVNA) of Geometric Mean Concentration (GMC)

  Days 4, 15, 43, 99, 183 and 365

• Percentage of Participants With Rabies Virus Neutralizing Activity (RVNA) ≥0.5 IU/mL

  Days 4, 8, 15, 43, 99, 183 and 365

• Area Under the Efficacy Curve for the Geometric Mean Concentration (GMC) of Rabies Virus Neutralizing Activity (RVNA)

  Day 1 to Day 15

Study Arms (2)

Experimental Group: SYN023+Rabies Vaccine

EXPERIMENTAL

SYN023: Interventions: are administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible SYN023 is an equal mass mixture of CTB011 and CTB012, two monoclonal antibodies that exhibit a wide spectrum of activity against various wild-type rabies strains in vitro. Dosage form: 6mg/2mL, liquid; Dosage: 0.3 mg/kg of SYN023; Frequency/duration: at Day 1 Rabies vaccine : Interventions: should be administered in deltoid muscle Dosage form: \>=2.5 IU, freeze-dried vaccine, reconstitute into 0.5 mL before use Dosage: 0.5 mL after reconstitution Frequency/duration: at Day 1, 4, 8, 15, 29

Biological: SYN023; Biological: Rabies Vaccine

Control Group: Human Rabies Immune Globulin (HRIG)+Rabies Vaccine

ACTIVE COMPARATOR

Human Rabies Immune Globulin (HRIG): Interventions: are administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible Dosage form: 100 IU/mL, liquid; Dosage: 20 IU/kg; Frequency/duration: at Day 1 Rabies vaccine : Interventions: should be administered in deltoid muscle Dosage form: \>=2.5 IU, freeze-dried vaccine, reconstitute into 0.5 mL before use; Dosage: 0.5 milliliters (mL) after reconstitution; Frequency/duration: at Day 1, 4, 8, 15, 29

Biological: Human Rabies Immune Globulin (HRIG); Biological: Rabies Vaccine

Interventions

SYN023 BIOLOGICAL

The finished product of SYN023 is a mixture of 3.0 mg/mL CTB011 and 3.0 mg/mL CTB012 at a ratio of 1:1. SYN023 is a sterile and preservative-free injection, and the excipient contains 25 mM histidine (3.879 mg/mL), 150 mM sodium chloride (8.766 mg/mL) and 0.02% polysorbate 80 (0.2 mg/mL) and pH of 6.0. Each vial contains 2.15 mL of SYN023, or 6.45 mg of monoclonal antibody. The glass bottle was closed with a 13 mm bromobutyl rubber stopper, a 13 mm aluminum crimping cap and a polypropylene flip-open lid.

Also known as: A Humanized Anti-Rabies Molecular antibodies cocktails

Experimental Group: SYN023+Rabies Vaccine

Human Rabies Immune Globulin (HRIG) BIOLOGICAL

The HRIG is a Chinese licensed Human Rabies Immunoglobulin, which are derived from human plasma, and then purified and filled in the injectable vial form. The HRIG is indicated for the Post-exposure Prophylactic (PEP) of Rabies

Control Group: Human Rabies Immune Globulin (HRIG)+Rabies Vaccine

Rabies Vaccine BIOLOGICAL

Interventions: The Chinese licensed rabies vaccine should be administered in deltoid muscle Dosage form: \>=2.5 IU, freeze-dried vaccine, reconstitute into 0.5 milliliters (mL) before use Dosage: 0.5 mL after reconstitution Frequency/duration: at Day 1, 4, 8, 15, 29

Also known as: Freeze-dried Rabies Vaccine for Human Use (Vero Cells)

Control Group: Human Rabies Immune Globulin (HRIG)+Rabies Vaccine; Experimental Group: SYN023+Rabies Vaccine

Eligibility Criteria

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

You may qualify if:

• Is age ≥18 years, on Study Day 1 with legal identification documents, and plan to live in the local administration area during the study;
• Category III rabies exposure within 24 hours before Study Drug receipt ;
• Completed written informed consent process, and signed the informed consent forms;
• Subjects with the ability to understand the study procedure. And agreed to complete all follow-ups;
• Female subjects are not in pregnancy (with negative results of urine pregnancy tests before vaccination) and are not in the period of breast feeding, and agree to avoid pregnancy within 121 days after administration;
• Those who have an armpit temperature ≤ 37.0 °C.

You may not qualify if:

• Previous receipt of equine or human (rabies) globulin or rabies vaccination prior to randomization;
• Clinical evidence of rabies infection;
• Category I and Category II rabies exposure;
• Had fever (armpit temperature ≥ 38.5 °C) within 3 days before Study Day 1, or in the acute episode of any chronic diseases;
• Received immunoglobulin or blood products (except for the anti-tetanus immunoglobulin) within 43 days before Study Day 1, or plan to use any such product (except for the anti-tetanus immunoglobulin) during the study;
• Received systemic immunosuppressant medication such as systemic corticosteroids but not limited to systemic corticosteroids within 43 days before Study Day 1;
• History of any immunodeficiency disease (for example: AIDS, systemic lupus erythematosus, etc.); or Laboratory evidence of previous or current immunodeficiency disease, including, but not limited to, any laboratory evidence of HIV infection;
• History of spleen function deficiency or function injury, such as no spleen caused by any cause (such as splenectomy);
• History of any severe allergy for vaccination, such as systemic urticaria, allergic laryngeal edema, anaphylactoid purpura, local allergic necrosis (Arthus reaction), angioedema, anaphylactic shock, etc., or allergic to any ingredient of the study drug/vaccine;
• Previous receipt of any study product (drug, vaccine, biological product or medical device) within 6 months before Study Day 1, or plan to participate in any other clinical study during this study period;
• History of or clinical evidence of any systemic disease, acute disease or chronic disease (such as convulsions, epilepsy, encephalopathy, nephrotic syndrome, etc.) that the investigator considers to be likely to interfere with safety or efficacy assessment of the study;
• Previous medical history that may compromise the safety of the subject in the study according to the opinion of the principal investigator.

Sponsors & Collaborators

• Synermore Biologics (Suzhou) Co., Ltd.: lead
• Simoon Record Pharma Information Consulting Co., Ltd.: collaborator

Study Sites (1)

Yunnan Province Center for Disease Control and Prevention (CDC)

Kunming, 650022, China

Location

Related Publications (4)

• McClain JB, Chuang A, Reid C, Moore SM, Tsao E. Rabies virus neutralizing activity, pharmacokinetics, and safety of the monoclonal antibody mixture SYN023 in combination with rabies vaccination: Results of a phase 2, randomized, blinded, controlled trial. Vaccine. 2021 Sep 24;39(40):5822-5830. doi: 10.1016/j.vaccine.2021.08.066. Epub 2021 Sep 3.

  PMID: 34483020 RESULT

• Ding Y, Wu M, Zhang H, Zhu X, Hu Y, Li X, Liu J, Tsao E, Liu M, Li C. Safety, pharmacokinetics and pharmacodynamics of SYN023 alone or in combination with a rabies vaccine: An open, parallel, single dose, phase 1 bridging study in healthy Chinese subjects. Antiviral Res. 2020 Dec;184:104956. doi: 10.1016/j.antiviral.2020.104956. Epub 2020 Oct 19.

  PMID: 33091433 RESULT

• Liu X, Zha Y, Wang Z, Jiang Y, Zhang X, Guo J, Li J, Zhang Q, Tsao E. The pharmacokinetics and safety comparison of Zamerovimab and Mazorelvimab monoclonal antibodies vs. HRIG in category III rabies post-exposure prophylaxis: a stratified analysis by wound characteristics. Biologicals. 2025 Nov;92:101852. doi: 10.1016/j.biologicals.2025.101852. Epub 2025 Aug 13.

  PMID: 40812204 DERIVED

• Liu X, Li J, Zha Y, Wang Z, Jiang Y, Zhang X, Guo J, Yu J, Li X, Zhang Q, Reid C, McClain JB, Tsao E. The efficacy and safety of SYN023 (Zamerovimab and Mazorelvimab injection), the recombinant humanized anti-rabies virus monoclonal antibody mixture, combined with rabies vaccine in a WHO category III rabies post-exposure population: A randomized, double-blind, positive control, phase III clinical trial. Vaccine. 2025 Aug 13;61:127289. doi: 10.1016/j.vaccine.2025.127289. Epub 2025 Jun 5.

  PMID: 40479926 DERIVED

MeSH Terms

Conditions

Rabies; Communicable Diseases; Virus Diseases; Rhabdoviridae Infections; Mononegavirales Infections; RNA Virus Infections

Interventions

Rabies Vaccines

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Director of Clinical Trials
• Organization: Synermore Biologics Co., Ltd.

xjli@synermore.cn

+86-512-87658266

Study Officials

• Xiaoqiang Liu, MD, PhD

  Yunnan Province CDC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinding for drugs were carried out by the randomization statistician and other personnel who will not be involved in the implementation of the clinical trial. Under the guidance of the randomization statistician, blinding operators attach the printed labels with numbers to the outer packages of the study drug/control drug according to the blind codes and seal the packages with sealing stickers. After the completion of blinding for drugs, the blind codes shall be sealed and kept by the randomization statistician. The entire blinding process must be documented. The personnel responsible for blinding must not participate in other relevant works during this clinical trial, and must not disclose the blind codes to any person participating in this clinical trial.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In this study, 1000 subjects aged 18 and over who had Grade 3 exposure to rabies virus were intended to be enrolled, and randomly assigned to the experimental group and the control group (3:1). Both groups were immunized according to PEP procedures for rabies.

Study Record Dates

• First Submitted: November 16, 2020
• First Posted: November 25, 2020
• Study Start: September 23, 2020
• Primary Completion: June 24, 2022
• Study Completion: December 16, 2022
• Last Updated: April 21, 2023
• Results First Posted: April 21, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)