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

NCT ID: NCT03961555

Last Updated: 2026-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 448 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-03
• Study Completion Date: 2021-12-23

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: EXPERIMENTAL

SYN023

Intervention Type: BIOLOGICAL

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

Rabies vaccine

Intervention Type: BIOLOGICAL

it should be administered in deltoid muscle

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)

Group Type: ACTIVE_COMPARATOR

HRIG (HyperRab)

Intervention Type: BIOLOGICAL

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

Rabies vaccine

Intervention Type: BIOLOGICAL

it should be administered in deltoid muscle

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

Group Type: EXPERIMENTAL

SYN023

Intervention Type: BIOLOGICAL

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

Rabies vaccine

Intervention Type: BIOLOGICAL

it should be administered in deltoid muscle

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

Group Type: ACTIVE_COMPARATOR

HRIG (HyperRab)

Intervention Type: BIOLOGICAL

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

Rabies vaccine

Intervention Type: BIOLOGICAL

it should be administered in deltoid muscle

Interventions

SYN023

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

Intervention Type: BIOLOGICAL

HRIG (HyperRab)

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

Intervention Type: BIOLOGICAL

Rabies vaccine

it should be administered in deltoid muscle

Intervention Type: BIOLOGICAL

Other Intervention Names

RabAvert; Rabipur

Eligibility Criteria

Inclusion Criteria

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

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Synermore Biologics USA Limited

UNKNOWN

Sponsor Role: collaborator

Synermore Biologics Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Florida

Gainesville, Florida, United States

University of Iowa

Iowa City, Iowa, United States

Clinical Research Solutions PC -Milan

Milan, Tennessee, United States

University of Virginia

Charlottesville, Virginia, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Baguio General Hospital and Medical Center

Baguio City, Benguet, Philippines

De La Salle Health Sciences Institute Independent Ethics Committee

Cavite City, Calabarzon, Philippines

Southern Philippines Medical Center

Davao City, Davao (Region XI), Philippines

Manila Doctors Hospital Institutional Review Board

Manila, National Capital Region, Philippines

Asian Hospital and Medical Center

Muntinlupa, National Capital Region, Philippines

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

Muntinlupa, National Capital Region, Philippines

Research Institute For Tropical Medicine

Muntinlupa, National Capital Region, Philippines

Far Eastern University Hospital Nicanor Reyes Medical Foundation

Quezon City, National Capital Region, Philippines

Mary Johnston Hospital

Manila, , Philippines

Countries

United States; Philippines

References

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.

Reference Type: DERIVED

PMID: 38834432 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SYN023-004

Identifier Type: -

Identifier Source: org_study_id