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

A Phase 2b Randomized Blinded Study to Evaluate SYN023 Compared to Human Rabies Immune Globulin in Post Exposure Prophylaxis of Rabies in Adults With Different Rabies Exposure Risks

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.

Study Overview

• Status: Completed
• Conditions: Rabies
• Intervention / Treatment: Biological: SYN023; Biological: Rabies vaccine; Biological: HRIG (HyperRab)

• Study Type: Interventional
• Enrollment (Actual): 448
• Phase: Phase 2

Contacts and Locations

Study Locations

• Philippines
  • Manila, Philippines
    • Mary Johnston Hospital
  • Benguet
    • Baguio City, Benguet, Philippines, 2600
      • Baguio General Hospital and Medical Center
  • Calabarzon
    • Cavite City, Calabarzon, Philippines, 4114
      • De La Salle Health Sciences Institute Independent Ethics Committee
  • Davao (Region XI)
    • Davao City, Davao (Region XI), Philippines, 8000
      • Southern Philippines Medical Center
  • National Capital Region
    • Manila, National Capital Region, Philippines, 1000
      • Manila Doctors Hospital Institutional Review Board
    • Muntinlupa, National Capital Region, Philippines, 1780
      • Asian Hospital and Medical Center
    • Muntinlupa, National Capital Region, Philippines, 1781
      • Center of Excellence in Drug Research, Evaluation and Studies, Inc.
    • Muntinlupa, National Capital Region, Philippines, 1781
      • Research Institute For Tropical Medicine
    • Quezon City, National Capital Region, Philippines, 1118
      • Far Eastern University Hospital Nicanor Reyes Medical Foundation
• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Tennessee
    • Milan, Tennessee, United States, 38358
      • Clinical Research Solutions PC -Milan
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (Low Risk Group):

Subjects must meet all of the following criteria at the time of subject ID assignment:

1. 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
2. Has completed the written informed consent process and signed informed consent document
3. Males and females
4. Is age equal or more than 18 years on Study Day 1
5. 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
6. Lives within 2 hour journey by available transportation to study center
7. 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

Inclusion Criteria (Normal Risk Group)

Subjects must meet all of the following criteria at the time of subject ID assignment:

1. 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)
2. Has completed the written informed consent process and signed informed consent document.
3. Males and females
4. Is age equal or more than 18 years on Study Day 1
5. 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
6. Lives within 2 hour journey by available transportation to study center
7. For female subjects: agrees to avoid pregnancy from 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

Exclusion Criteria:

Subjects must have had none of the following at the time of subject ID assignment:

1. Clinical evidence of rabies infection
2. Category 3 exposure > 54 hours before Study Drug receipt
3. History or serological evidence of previous rabies vaccination
4. Previous receipt of equine or human rabies globulin
5. History of hypersensitivity reaction to equine or human immunoglobulin.
6. Received immunoglobulin or blood products within 42 days before Study Day 1
7. Received any investigational drug therapy or investigational vaccine within 60 days before Study Day 1
8. Planned participation in any other investigational study during the study period.
9. Receiving systemic immunosuppressant medication such as systemic corticosteroids but not limited to systemic corticosteroids
10. History or laboratory evidence of any past, present, or possible immunodeficiency state including but not limited to any laboratory indication of HIV infection
11. Previous medical history that may compromise the safety of the subject in the study according to the opinion of the principal investigator
12. 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
13. Pregnancy (results of the urine pregnancy test MUST be known before enrollment)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Risk Group: SYN023+Rabies vaccine; 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; it is administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible; Biological: Rabies vaccine; it should be administered in deltoid muscle; Other Names: RabAvert; Rabipur
Active Comparator: Low Risk Group: Human Rabies Immune Globulin (HRIG)+Rabies vaccine; 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: Rabies vaccine; it should be administered in deltoid muscle; Other Names: RabAvert; Rabipur; Biological: HRIG (HyperRab); it is administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible
Experimental: Normal Risk Group: SYN023+Rabies vaccine; 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; it is administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible; Biological: Rabies vaccine; it should be administered in deltoid muscle; Other Names: RabAvert; Rabipur
Active Comparator: Normal Risk Group: Human Rabies Immune Globulin (HRIG)+Rabies vaccine; 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: Rabies vaccine; it should be administered in deltoid muscle; Other Names: RabAvert; Rabipur; Biological: HRIG (HyperRab); it is administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Efficacy Curve for the Geometric Mean Concentration (GMC) of Rabies Virus Neutralizing Activity (RVNA)	Rabies Virus Neutralizing Activity (RVNA) was assessed using Rapid Fluorescent Focus Inhibition Test (RFFIT). Area Under the Efficacy Curve for the GMC of RVNA from Study Day 1 to Day 15 after administration (AUEC1-15)	Day 1 to Day 15
Rabies Virus Neutralizing Activity (RVNA) of Geometric Mean Concentration (GMC) at Study Day 4	Rabies Virus Neutralizing Activity (RVNA) was assessed using Rapid Fluorescent Focus Inhibition Test (RFFIT).	Day 4
Maximum Observed Serum Concentration (Cmax)	The Cmax of CTB011 and CTB012 derived from non-compartmental analysis.	Day 1 to Day 99
Time of Maximum Observed Serum Concentration (Tmax)	The Tmax of CTB011 and CTB012 derived from non-compartmental analysis.	Day 1 to Day 99

Collaborators and Investigators

• Sponsor: Synermore Biologics Co., Ltd.
• Collaborators: Synermore Biologics USA Limited

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2019
• Primary Completion (Actual): December 23, 2021
• Study Completion (Actual): December 23, 2021

Study Registration Dates

• First Submitted: May 16, 2019
• First Submitted That Met QC Criteria: May 21, 2019
• First Posted (Actual): May 23, 2019

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: December 26, 2025
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Post-exposure prophylaxis of Rabies
• Additional Relevant MeSH Terms: Infections; RNA Virus Infections; Virus Diseases; Mononegavirales Infections; Rhabdoviridae Infections; Rabies; Biological Products; Complex Mixtures; Vaccines; Viral Vaccines; Rabies Vaccines
• Other Study ID Numbers: SYN023-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No