Comparison of SYN023 to Human Rabies Immune Globulin in Post Exposure Prophylaxis of Rabies

NCT03961555 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: SYN023-004
• Study Type: interventional
• Target: 448
• Locations: 2 countries
• Sites: 14

Brief Summary

This is a Phase 2b, double blinded, randomized study of SYN023 compared to HyperRab® (a licensed Rabies immune globulin from human sources, HRIG) for the prevention of rabies as part of post-exposure prophylaxis (PEP). The trial will enroll sequentially two different risk substrata of WHO Category 3 rabies exposure which are Low Risk Group (LRG) and Normal Risk Group (NRG). The enrollment will be stepwise while subject's data will be reviewed by data and safety monitoring board (DSMB) to confirm the safety and permit for next enrollment. Besides, rabies vaccine would be administered within 75 minutes 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 the United States.

Conditions

Rabies

Keywords

Post-exposure prophylaxis of Rabies

Outcome Measures

Primary Outcomes (4)

• 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

• Rabies Virus Neutralizing Activity (RVNA) of Geometric Mean Concentration (GMC) at Study Day 99

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

  Day 99

• Percentage of Participants With Rabies Virus Neutralizing Activity (RVNA) ≥0.5 IU/mL at Study Day 99

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

  Day 99

• Number of Probable or Confirmed Rabies Cases

  Case Classification Human Rabies * Suspected: A case that is compatible with the clinical case definition * Probable: A suspected case (above) plus history of contact with a suspected rabid animal. * Confirmed: A suspected case that is laboratory-confirmed.

  Day 1 to Day 365

Secondary Outcomes (4)

• Rabies Virus Neutralizing Activity (RVNA) of Geometric Mean Concentration (GMC) at Study Day 4

  Day 4

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

  Day 1 to Day 15

• Maximum Observed Serum Concentration (Cmax)

  Day 1 to Day 99

• Time of Maximum Observed Serum Concentration (Tmax)

  Day 1 to Day 99

Study Arms (4)

Low Risk Group: SYN023+Rabies vaccine

EXPERIMENTAL

The subjects were enrolled in the study sequentially into 2 different risk substrata of WHO Category 3 rabies exposure, which included Low Risk Group (LRG) and Normal Risk Group (NRG). Bites to the head, neck, genitalia arm or hand are not included in the LRG. The initial 20 subjects in the LRG were to be randomized on a 3:1 (SYN023 to Human Rabies Immune Globulin (HRIG)) ratio. The general 60 subjects in the LRG were to be allocated with a 1:1 randomization to either SYN023 or HRIG treatment arms. SYN023: * Interventions: are administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible * Dosage: 0.3 mg/kg of SYN023 * Frequency/duration: at Day 1 Rabies vaccine: * Interventions: should be administered in deltoid muscle * Dosage: 1 mL after reconstitution * Frequency/duration: Initial LRG subjects received 4 vaccine doses (Days 1, 4, 8,15); General LRG subjects received 5 vaccine doses (Days 1, 4, 8, 15, and 29).

Biological: SYN023; Biological: Rabies vaccine

Low Risk Group: Human Rabies Immune Globulin (HRIG)+Rabies vaccine

ACTIVE COMPARATOR

The subjects were enrolled in the study sequentially into 2 different risk substrata of WHO Category 3 rabies exposure, which included Low Risk Group (LRG) and Normal Risk Group (NRG). Bites to the head, neck, genitalia arm or hand are not included in the LRG. The initial 20 subjects in the LRG were to be randomized on a 3:1 (SYN023 to Human Rabies Immune Globulin (HRIG)) ratio. The general 60 subjects in the LRG were to be allocated with a 1:1 randomization to either SYN023 or HRIG treatment. HRIG: * Interventions: are administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible * Dosage: 20 IU/kg * Frequency/duration: at Day 1 Rabies vaccine : * Interventions: should be administered in deltoid muscle * Dosage: 1 mL after reconstitution * Frequency/duration: Initial LRG subjects received 4 vaccine doses (Days 1, 4, 8,15); General LRG subjects received 5 vaccine doses (Days 1, 4, 8, 15, and 29)

Biological: HRIG (HyperRab); Biological: Rabies vaccine

Normal Risk Group: SYN023+Rabies vaccine

EXPERIMENTAL

The subjects were enrolled in the study sequentially into 2 different risk substrata of WHO Category 3 rabies exposure, which included Low Risk Group (LRG) and Normal Risk Group (NRG). The NRG were consisted of all WHO Category 3 exposure. Subjects were to be allocated with a 1:1 randomization to either SYN023 or Human Rabies Immune Globulin (HRIG) treatment arms. SYN023: * Interventions: are administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible * Dosage: 0.3 mg/kg of SYN023 * Frequency/duration: at Day 1 Rabies vaccine: * Interventions: should be administered in deltoid muscle * Dosage: 1 mL after reconstitution * Frequency/duration: at Day 1, 4, 8, 15, 29

Biological: SYN023; Biological: Rabies vaccine

Normal Risk Group: Human Rabies Immune Globulin (HRIG)+Rabies vaccine

ACTIVE COMPARATOR

The subjects were enrolled in the study sequentially into 2 different risk substrata of WHO Category 3 rabies exposure, which included Low Risk Group (LRG) and Normal Risk Group (NRG). The NRG were consisted of all WHO Category 3 exposure. Subjects were to be allocated with a 1:1 randomization to either SYN023 or Human Rabies Immune Globulin (HRIG) treatment arms. HRIG: * Interventions: are administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible * Dosage: 20 IU/kg * Frequency/duration: at Day 1 Rabies vaccine (RabAvert/Rabipur): * Interventions: should be administered in deltoid muscle * Dosage: 1 mL after reconstitution * Frequency/duration: at Day 1, 4, 8, 15, 29

Biological: HRIG (HyperRab); Biological: Rabies vaccine

Interventions

SYN023 BIOLOGICAL

it is administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible

Low Risk Group: SYN023+Rabies vaccine; Normal Risk Group: SYN023+Rabies vaccine

HRIG (HyperRab) BIOLOGICAL

it is administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible

Low Risk Group: Human Rabies Immune Globulin (HRIG)+Rabies vaccine; Normal Risk Group: Human Rabies Immune Globulin (HRIG)+Rabies vaccine

Rabies vaccine BIOLOGICAL

it should be administered in deltoid muscle

Also known as: RabAvert, Rabipur

Low Risk Group: Human Rabies Immune Globulin (HRIG)+Rabies vaccine; Low Risk Group: SYN023+Rabies vaccine; Normal Risk Group: Human Rabies Immune Globulin (HRIG)+Rabies vaccine; Normal Risk 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:

• Subjects must meet all of the following criteria at the time of subject ID assignment:
• History of dog, cat, mongoose, fox, ferret, skunk, bat or raccoon bite to trunk, leg, ankle or foot, or lick or scratch with, or of broken skin or mucous membrane saliva or neural tissue contamination, unprotected physical bat contact, scratch or saliva contamination of the head or neck without broken skin all ≤ 54 hours
• Has completed the written informed consent process and signed informed consent document
• Males and females
• Is age equal or more than 18 years on Study Day 1
• Agrees to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study
• Lives within 2 hour journey by available transportation to study center
• For female subjects: agrees to avoid pregnancy from Study Day 1 through Study Day 121. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, intrauterine device (IUD), or the combination of a condom or diaphragm with spermicide
• Subjects must meet all of the following criteria at the time of subject ID assignment:
• History of dog, cat, mongoose, fox, ferret, skunk, bat or raccoon bite to any body part, lick or scratch with, or of broken skin, mucous membrane saliva or neural tissue contamination, or unprotected physical bat contact all ≤ 54 hours from post exposure prophylaxis (PEP)
• Has completed the written informed consent process and signed informed consent document.
• Males and females
• Is age equal or more than 18 years on Study Day 1
• Agrees to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study
• Lives within 2 hour journey by available transportation to study center

You may not qualify if:

• Subjects must have had none of the following at the time of subject ID assignment:
• Clinical evidence of rabies infection
• Category 3 exposure \> 54 hours before Study Drug receipt
• History or serological evidence of previous rabies vaccination
• Previous receipt of equine or human rabies globulin
• History of hypersensitivity reaction to equine or human immunoglobulin.
• Received immunoglobulin or blood products within 42 days before Study Day 1
• Received any investigational drug therapy or investigational vaccine within 60 days before Study Day 1
• Planned participation in any other investigational study during the study period.
• Receiving systemic immunosuppressant medication such as systemic corticosteroids but not limited to systemic corticosteroids
• History or laboratory evidence of any past, present, or possible immunodeficiency state including but not limited to any laboratory indication of HIV infection
• Previous medical history that may compromise the safety of the subject in the study according to the opinion of the principal investigator
• History or evidence on physical examination of any systemic disease or any acute or chronic illness that, in the opinion of the investigator, may interfere with the evaluation of the safety or activity of SYN023
• Pregnancy (results of the urine pregnancy test MUST be known before enrollment)

Sponsors & Collaborators

• Synermore Biologics Co., Ltd.: lead
• Synermore Biologics USA Limited: collaborator

Study Sites (14)

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Clinical Research Solutions PC -Milan

Milan, Tennessee, 38358, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Baguio General Hospital and Medical Center

Baguio City, Benguet, 2600, Philippines

Location

De La Salle Health Sciences Institute Independent Ethics Committee

Cavite City, Calabarzon, 4114, Philippines

Location

Southern Philippines Medical Center

Davao City, Davao (Region XI), 8000, Philippines

Location

Manila Doctors Hospital Institutional Review Board

Manila, National Capital Region, 1000, Philippines

Location

Asian Hospital and Medical Center

Muntinlupa, National Capital Region, 1780, Philippines

Location

Center of Excellence in Drug Research, Evaluation and Studies, Inc.

Muntinlupa, National Capital Region, 1781, Philippines

Location

Research Institute For Tropical Medicine

Muntinlupa, National Capital Region, 1781, Philippines

Location

Far Eastern University Hospital Nicanor Reyes Medical Foundation

Quezon City, National Capital Region, 1118, Philippines

Location

Mary Johnston Hospital

Manila, Philippines

Location

Related Publications (1)

• Quiambao BP, Payumo RA, Roa C, Borja-Tabora CF, Emmeline Montellano M, Reyes MRL, Zoleta-De Jesus L, Capeding MR, Solimen DP, Barez MY, Reid C, Chuang A, Tsao E, McClain JB. A phase 2b, Randomized, double blinded comparison of the safety and efficacy of the monoclonal antibody mixture SYN023 and human rabies immune globulin in patients exposed to rabies. Vaccine. 2024 Sep 17;42(22):126018. doi: 10.1016/j.vaccine.2024.05.066. Epub 2024 Jun 4.

  PMID: 38834432 DERIVED

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

Results Point of Contact

• Title: Ariel Chuang / Director
• Organization: Synermore Biologics Co., Ltd.

achuang@synermore.com

+886 22659 0988

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2019
• First Posted: May 23, 2019
• Study Start: September 3, 2019
• Primary Completion: December 23, 2021
• Study Completion: December 23, 2021
• Last Updated: January 16, 2026
• Results First Posted: January 16, 2026

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); PH (9)