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

Synermore Biologics

Status and phase: Completed; Phase 2

Conditions: Rabies

Treatments: Biological: Rabies vaccine; Biological: SYN023; Biological: HRIG (HyperRab)

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT03961555

SYN023-004

Details and patient eligibility

About

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 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.

Enrollment: 448 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria (LRG):

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 (Section 3.9.4 and 3.9.5)
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 (NRG)

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 PEP (Section 3.9.4 and 3.9.5)
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)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

448 participants in 2 patient groups

SYN023+Rabies vaccine

Experimental group

Description:

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

Treatment:

Biological: SYN023

Biological: Rabies vaccine

HRIG+Rabies vaccine

Active Comparator group

Description:

HRIG: * Interventions: are administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible * Dosage form: 150 IU/mL or 300 IU/mL, liquid, * Dosage: 20 IU/kg of HyperRab (HRIG) * Frequency/duration: at Day 1 Rabies vaccine (RabAvert/Rabipur): * Interventions: should be administered in deltoid muscle * Dosage form: \>=2.5 IU, freeze-dried vaccine, reconstitute into 1mL before use * Dosage: 1 mL after reconstitution * Frequency/duration: at Day 1, 4, 8, 15, 29

Treatment:

Biological: HRIG (HyperRab)

Biological: Rabies vaccine