A Phase III Clinical Study to Evaluate SYN023's Efficacy and Safety
Condition: Rabies; Communicable Disease; Virus Diseases; Rhabdoviridae Infections; Mononegavirales Infections; RNA Virus Infections
MeSH terms: Infections; Communicable Diseases; Virus Diseases; Rabies; RNA Virus Infections; Mononegavirales Infections; Rhabdoviridae Infections
Intervention: SYN023; Human Rabies Immune Globulin (HRIG); Rabies Vaccine
Intervention description: 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.; 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; 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
Intervention MeSH terms: Vaccines; Immunoglobulins; Antibodies; gamma-Globulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: 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.
Enrollment: 1000.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Post-exposure prophylaxis of Rabies

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Is age ≥18 years, on Study Day 1 with legal identification documents, and plan to live
             in the local administration area during the study;

          2. Category III rabies exposure within 24 hours before Study Drug receipt ;

          3. Completed written informed consent process, and signed the informed consent forms;

          4. Subjects with the ability to understand the study procedure. And agreed to complete
             all follow-ups;

          5. 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;

          6. Those who have an armpit temperature ≤ 37.0 °C.

        Exclusion Criteria:

          1. Previous receipt of equine or human (rabies) globulin or rabies vaccination prior to
             randomization;

          2. Clinical evidence of rabies infection;

          3. Category I and Category II rabies exposure;

          4. Had fever (armpit temperature ≥ 38.5 °C) within 3 days before Study Day 1, or in the
             acute episode of any chronic diseases;

          5. 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;

          6. Received systemic immunosuppressant medication such as systemic corticosteroids but
             not limited to systemic corticosteroids within 43 days before Study Day 1;

          7. 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;

          8. History of spleen function deficiency or function injury, such as no spleen caused by
             any cause (such as splenectomy);

          9. 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;

         10. 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;

         11. 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;

         12. Previous medical history that may compromise the safety of the subject in the study
             according to the opinion of the principal investigator.