Clinical trial NCT03961555: Comparison of SYN023 to Human Rabies Immune Globulin in Post Exposure Prophylaxis of Rabies
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rabies
Keywords: Post-exposure prophylaxis of Rabies
Lead sponsor: Synermore Biologics Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Synermore Biologics USA Limited
First posted: 2019-05-23
Enrollment: 448
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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 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.


Eligibility 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)

Primary outcomes:
measure: geometric mean RVNA concentration (superiority)
timeFrame: Day 1 and 8
measure: geometric mean RVNA concentrations at D99
timeFrame: Day 1 and 99
measure: cases of probable or confirmed rabie
timeFrame: Day 1, 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365
measure: the percentage of subjects with RVNA concentration ≥0.5 IU/mL
timeFrame: D1 and 99
Secondary outcomes:
measure: geometric mean RVNA concentration on Day 4
timeFrame: Day 1 and 4
measure: The ratio of the geometric mean concentrations of RVNA at each time point in geometric mean RVNA AUEC1-15
timeFrame: Day 1, 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365
measure: geometric mean concentrations of RVNA at each time point
timeFrame: Day 1, 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365
measure: the percentage of RVNA concentration ≥0.5 IU/mL at each time point
timeFrame: Day 1, 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365
measure: PK for Vd of SYN023 using non-compartmental analysis
timeFrame: Day 1, 4, 8, 15, 99
measure: PK for Cmax of SYN023 using non-compartmental analysis
timeFrame: Day 1, 4, 8, 15, 99
measure: PK for Tmax of SYN023 using non-compartmental analysis
timeFrame: Day 1, 4, 8, 15, 99
measure: PK for AUC1-t of SYN023 using non-compartmental analysis
timeFrame: Day 1, 4, 8, 15, 99
measure: PK for AUC1-inf of SYN023 using non-compartmental analysis
timeFrame: Day 1, 4, 8, 15, 99
measure: PK for t½ of SYN023 using non-compartmental analysis
timeFrame: Day 1, 4, 8, 15, 99
measure: PK for Cl of SYN023 using non-compartmental analysis
timeFrame: Day 1, 4, 8, 15, 99
measure: PK for λz of SYN023 using non-compartmental analysis
timeFrame: Day 1, 4, 8, 15, 99
measure: The presence and effects of anti-SYN023 antibodies
timeFrame: Day 1, 15, 29, and 99 for LRG group and Day 1, 15 and 99 for NRG group
measure: the safety (the number and percentage of adverse events) of SYN023 compared to HRIG
timeFrame: Day 1, 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365
measure: effect of increasing BMI
timeFrame: Day 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Milan
country: United States
facility: Clinical Research Solutions PC -Milan
state: Tennessee
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Baguio City
country: Philippines
facility: Baguio General Hospital and Medical Center
state: Benguet
city: Cavite
country: Philippines
facility: De La Salle Health Sciences Institute Independent Ethics Committee
state: Calabarzon
city: Davao City
country: Philippines
facility: Southern Philippines Medical Center
state: Davao (Region XI)
city: Manila
country: Philippines
facility: Manila Doctors Hospital Institutional Review Board
state: Metro Manila
city: Muntinlupa
country: Philippines
facility: Asian Hospital and Medical Center
state: National Capital Region
city: Muntinlupa
country: Philippines
facility: Center of Excellence in Drug Research, Evaluation and Studies, Inc.
state: National Capital Region
city: Muntinlupa
country: Philippines
facility: Research Institute For Tropical Medicine
state: National Capital Region
city: Quezon City
country: Philippines
facility: Far Eastern University Hospital Nicanor Reyes Medical Foundation
state: National Capital Region
city: Manila
country: Philippines
facility: Mary Johnston Hospital
Study officials:
References: