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

Rabies Clinical Trial

— ARPEP  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03961555
• Other study ID #: SYN023-004
• Status: Completed
• Phase: Phase 2
• Start date: September 3, 2019
• Est. completion date: December 23, 2021

Study information

• Verified date: September 2022
• Source: Synermore Biologics Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 448
• Est. completion date: December 23, 2021
• Est. primary completion date: December 23, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Rabies

Intervention

Biological:
• SYN023
it is administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible
• HRIG (HyperRab)
it is administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible
• Rabies vaccine
it should be administered in deltoid muscle

Locations

Country	Name	City	State
Philippines	Baguio General Hospital and Medical Center	Baguio City	Benguet
Philippines	De La Salle Health Sciences Institute Independent Ethics Committee	Cavite	Calabarzon
Philippines	Southern Philippines Medical Center	Davao City	Davao (Region XI)
Philippines	Manila Doctors Hospital Institutional Review Board	Manila	Metro Manila
Philippines	Mary Johnston Hospital	Manila
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
United States	University of Virginia	Charlottesville	Virginia
United States	University of Florida	Gainesville	Florida
United States	University of Iowa	Iowa City	Iowa
United States	Clinical Research Solutions PC -Milan	Milan	Tennessee
United States	Medical College of Wisconsin	Milwaukee	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Synermore Biologics Co., Ltd.	Synermore Biologics USA Limited

Countries where clinical trial is conducted

United States,  Philippines, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	geometric mean RVNA concentration (superiority)	To demonstrate that the geometric mean RVNA concentration for SYN023 recipients is superior to the geometric mean RVNA concentration for HRIG recipients on Study Day 8	Day 1 and 8
Primary	geometric mean RVNA concentrations at D99	To demonstrate that the Study Day 99 geometric mean RVNA concentration for SYN023 recipients is not inferior to the geometric mean RVNA concentration for HRIG recipients	Day 1 and 99
Primary	cases of probable or confirmed rabie	There are no cases of probable or confirmed rabies in SYN023 recipients	Day 1, 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365
Primary	the percentage of subjects with RVNA concentration =0.5 IU/mL	To demonstrate that the percentage of subjects with RVNA concentration =0.5 IU/mL on Study Day 99 in SYN023 recipients is not inferior to the percentage of recipients with RVNA concentration =0.5 IU/mL for HRIG	D1 and 99
Secondary	geometric mean RVNA concentration on Day 4	To demonstrate that the geometric mean RVNA concentration for SYN023 is superior to the geometric mean RVNA concentration for HRIG on Study Day 4	Day 1 and 4
Secondary	The ratio of the geometric mean concentrations of RVNA at each time point in geometric mean RVNA AUEC1-15	To demonstrate that the geometric mean RVNA AUEC1-15 for SYN023 is superior to the geometric mean RVNA AUEC1-15 for HRIG	Day 1, 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365
Secondary	geometric mean concentrations of RVNA at each time point	To describe the ratio of the geometric mean concentrations of RVNA at each time point in SYN023 recipients divided by the geometric mean concentrations of RVNA in HRIG recipients for LRG and NRG in the per-protocol and as-treated populations	Day 1, 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365
Secondary	the percentage of RVNA concentration =0.5 IU/mL at each time point	To describe the percentage of RVNA concentration =0.5 IU/mL at each time point for SYN023 and HRIG recipients for LRG and NRG in the per-protocol and as-treated populations.	Day 1, 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365
Secondary	PK for Vd of SYN023 using non-compartmental analysis	To describe the pharmacokinetics of SYN023 Mab using non-compartmental analysis. Vd will be calculated when possible in the LRG and NRG protocol and as treated populations	Day 1, 4, 8, 15, 99
Secondary	PK for Cmax of SYN023 using non-compartmental analysis	To describe the pharmacokinetics of SYN023 Mab using non-compartmental analysis. Cmax will be calculated when possible in the LRG and NRG protocol and as treated populations	Day 1, 4, 8, 15, 99
Secondary	PK for Tmax of SYN023 using non-compartmental analysis	To describe the pharmacokinetics of SYN023 Mab using non-compartmental analysis. Tmax will be calculated when possible in the LRG and NRG protocol and as treated populations	Day 1, 4, 8, 15, 99
Secondary	PK for AUC1-t of SYN023 using non-compartmental analysis	To describe the pharmacokinetics of SYN023 Mab using non-compartmental analysis. AUC1-t will be calculated when possible in the LRG and NRG protocol and as treated populations	Day 1, 4, 8, 15, 99
Secondary	PK for AUC1-inf of SYN023 using non-compartmental analysis	To describe the pharmacokinetics of SYN023 Mab using non-compartmental analysis. AUC1-inf will be calculated when possible in the LRG and NRG protocol and as treated populations	Day 1, 4, 8, 15, 99
Secondary	PK for t½ of SYN023 using non-compartmental analysis	To describe the pharmacokinetics of SYN023 Mab using non-compartmental analysis. t½ will be calculated when possible in the LRG and NRG protocol and as treated populations	Day 1, 4, 8, 15, 99
Secondary	PK for Cl of SYN023 using non-compartmental analysis	To describe the pharmacokinetics of SYN023 Mab using non-compartmental analysis. Cl will be calculated when possible in the LRG and NRG protocol and as treated populations	Day 1, 4, 8, 15, 99
Secondary	PK for ?z of SYN023 using non-compartmental analysis	To describe the pharmacokinetics of SYN023 Mab using non-compartmental analysis. ?z will be calculated when possible in the LRG and NRG protocol and as treated populations	Day 1, 4, 8, 15, 99
Secondary	The presence and effects of anti-SYN023 antibodies	To evaluate presence and effects of anti-SYN023 antibodies (anti-CTB011, anti-CTB012)	Day 1, 15, 29, and 99 for LRG group and Day 1, 15 and 99 for NRG group
Secondary	the safety (the number and percentage of adverse events) of SYN023 compared to HRIG	To evaluate the safety of SYN023 compared to HyperRab® S/D. The safety profile will be the number and percentage of unsolicited and solicited adverse events recorded at all available post-vaccination time points	Day 1, 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365
Secondary	effect of increasing BMI	To describe any effect of increasing BMI on SYN023 and RVNA concentrations	Day 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365