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

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ClinicalTrials.gov Identifier: NCT03961555
Recruitment Status : Active, not recruiting
First Posted : May 23, 2019
Last Update Posted : December 31, 2020
Sponsor:
Information provided by (Responsible Party):
Synermore Biologics Co., Ltd.

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.


Condition or disease Intervention/treatment Phase
Rabies Biological: SYN023 Biological: HRIG (HyperRab) Biological: Rabies vaccine Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 448 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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
Actual Study Start Date : September 3, 2019
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Rabies

Arm Intervention/treatment
Experimental: SYN023+Rabies vaccine

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
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: HRIG+Rabies vaccine

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
Biological: HRIG (HyperRab)
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




Primary Outcome Measures :
  1. geometric mean RVNA concentration (superiority) [ Time Frame: Day 1 and 8 ]
    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

  2. geometric mean RVNA concentrations at D99 [ Time Frame: Day 1 and 99 ]
    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

  3. cases of probable or confirmed rabie [ Time Frame: Day 1, 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365 ]
    There are no cases of probable or confirmed rabies in SYN023 recipients

  4. the percentage of subjects with RVNA concentration ≥0.5 IU/mL [ Time Frame: D1 and 99 ]
    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


Secondary Outcome Measures :
  1. geometric mean RVNA concentration on Day 4 [ Time Frame: Day 1 and 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

  2. The ratio of the geometric mean concentrations of RVNA at each time point in geometric mean RVNA AUEC1-15 [ Time Frame: Day 1, 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365 ]
    To demonstrate that the geometric mean RVNA AUEC1-15 for SYN023 is superior to the geometric mean RVNA AUEC1-15 for HRIG

  3. geometric mean concentrations of RVNA at each time point [ Time Frame: Day 1, 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365 ]
    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

  4. the percentage of RVNA concentration ≥0.5 IU/mL at each time point [ Time Frame: Day 1, 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365 ]
    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.

  5. PK for Vd of SYN023 using non-compartmental analysis [ Time Frame: Day 1, 4, 8, 15, 99 ]
    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

  6. PK for Cmax of SYN023 using non-compartmental analysis [ Time Frame: Day 1, 4, 8, 15, 99 ]
    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

  7. PK for Tmax of SYN023 using non-compartmental analysis [ Time Frame: Day 1, 4, 8, 15, 99 ]
    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

  8. PK for AUC1-t of SYN023 using non-compartmental analysis [ Time Frame: Day 1, 4, 8, 15, 99 ]
    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

  9. PK for AUC1-inf of SYN023 using non-compartmental analysis [ Time Frame: Day 1, 4, 8, 15, 99 ]
    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

  10. PK for t½ of SYN023 using non-compartmental analysis [ Time Frame: Day 1, 4, 8, 15, 99 ]
    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

  11. PK for Cl of SYN023 using non-compartmental analysis [ Time Frame: Day 1, 4, 8, 15, 99 ]
    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

  12. PK for λz of SYN023 using non-compartmental analysis [ Time Frame: Day 1, 4, 8, 15, 99 ]
    To describe the pharmacokinetics of SYN023 Mab using non-compartmental analysis. λz will be calculated when possible in the LRG and NRG protocol and as treated populations

  13. The presence and effects of anti-SYN023 antibodies [ Time Frame: Day 1, 15, 29, and 99 for LRG group and Day 1, 15 and 99 for NRG group ]
    To evaluate presence and effects of anti-SYN023 antibodies (anti-CTB011, anti-CTB012)

  14. the safety (the number and percentage of adverse events) of SYN023 compared to HRIG [ Time Frame: Day 1, 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365 ]
    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

  15. effect of increasing BMI [ Time Frame: Day 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365 ]
    To describe any effect of increasing BMI on SYN023 and RVNA concentrations



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03961555


Locations
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United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Tennessee
Clinical Research Solutions PC -Milan
Milan, Tennessee, United States, 38358
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22903
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Philippines
Baguio General Hospital and Medical Center
Baguio City, Benguet, Philippines, 2600
De La Salle Health Sciences Institute Independent Ethics Committee
Cavite, Calabarzon, Philippines, 4114
Southern Philippines Medical Center
Davao City, Davao (Region XI), Philippines, 8000
Manila Doctors Hospital Institutional Review Board
Manila, Metro Manila, Philippines, 1000
Asian Hospital and Medical Center
Muntinlupa, National Capital Region, Philippines, 1780
Center of Excellence in Drug Research, Evaluation and Studies, Inc.
Muntinlupa, National Capital Region, Philippines, 1781
Research Institute For Tropical Medicine
Muntinlupa, National Capital Region, Philippines, 1781
Far Eastern University Hospital Nicanor Reyes Medical Foundation
Quezon City, National Capital Region, Philippines, 1118
Mary Johnston Hospital
Manila, Philippines
Sponsors and Collaborators
Synermore Biologics Co., Ltd.
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Responsible Party: Synermore Biologics Co., Ltd.
ClinicalTrials.gov Identifier: NCT03961555    
Other Study ID Numbers: SYN023-004
First Posted: May 23, 2019    Key Record Dates
Last Update Posted: December 31, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Synermore Biologics Co., Ltd.:
Post-exposure prophylaxis of Rabies
Additional relevant MeSH terms:
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Rabies
Rhabdoviridae Infections
Mononegavirales Infections
RNA Virus Infections
Virus Diseases