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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 : Not yet recruiting
First Posted : May 23, 2019
Last Update Posted : May 23, 2019
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)
Estimated 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
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : November 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
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
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 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

  2. geometric mean RVNA concentrations at D99 [ Time Frame: Day 1 and 99 ]
    To demonstrate that the geometric mean RVNA concentrations for SYN023 on Study Day 99 is not inferior to the geometric mean RVNA concentration for HRIG

  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


Secondary Outcome Measures :
  1. the proportion of SYN023 recipients with blood RVNA concentrations ≥ 0.5 IU/mL is not inferior to HRIG recipients [ Time Frame: Day 1, 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365 ]
    To demonstrate that the proportion of SYN023 recipients with blood RVNA concentrations that meet the generally accepted as adequate threshold ≥ 0.5 IU/mL, for the duration of the trial in the per-protocol population is not inferior to the same proportion in HRIG recipients

  2. The ratio of the geometric mean concentrations of RVNA at each time point in SYN023 recipients/HRIG recipients [ 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 the per-protocol and as-treated populations

  3. Compare the AUEC1-8 and AUEC1-15 pharmacodynamic intervals for SYN023 recipients to HRIG recipients in PP population [ Time Frame: Day 1, 4, 8, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365 ]
    Compare the AUEC1-8 and AUEC1-15 pharmacodynamic intervals for SYN023 recipients to AUEC1-8 and AUEC1-15 for HRIG recipients in the per-protocol population

  4. PK for Vd of SYN023 using non-compartmental analysis [ Time Frame: 71 days in LRG group ]
    To describe the pharmacokinetics for Vd of SYN023 using non-compartmental analysis when possible in the LRG per-protocol and as treated populations

  5. PK for Cmax of SYN023 using non-compartmental analysis [ Time Frame: 71 days in LRG group ]
    To describe the pharmacokinetics of SYN023 using non-compartmental analysis. Cmax will be calculated when possible in the LRG per-protocol and as treated populations

  6. PK for Tmax of SYN023 using non-compartmental analysis [ Time Frame: 71 days in LRG group ]
    To describe the pharmacokinetics for Tmax of SYN023 using non-compartmental analysis when possible in the LRG per-protocol and as treated populations

  7. PK for AUC1-t of SYN023 using non-compartmental analysis [ Time Frame: 71 days in LRG group ]
    To describe the pharmacokinetics for AUC1-t of SYN023 using non-compartmental analysis when possible in the LRG per-protocol and as treated populations

  8. PK for AUC1-inf of SYN023 using non-compartmental analysis [ Time Frame: 71 days in LRG group ]
    To describe the pharmacokinetics for AUC1-inf of SYN023 using non-compartmental analysis when possible in the LRG per-protocol and as treated populations

  9. PK for t½ of SYN023 using non-compartmental analysis [ Time Frame: 71 days in LRG group ]
    To describe the pharmacokinetics for t½ of SYN023 using non-compartmental analysis when possible in the LRG per-protocol and as treated populations

  10. PK for Cl of SYN023 using non-compartmental analysis [ Time Frame: 71 days in LRG group ]
    To describe the pharmacokinetics for Cl of SYN023 using non-compartmental analysis when possible in the LRG per-protocol and as treated populations

  11. PK for λz of SYN023 using non-compartmental analysis [ Time Frame: 71 days in LRG group ]
    To describe the pharmacokinetics for λz of SYN023 using non-compartmental analysis when possible in the LRG per-protocol and as treated populations

  12. The presence and effects of anti-SYN023 antibodies [ Time Frame: Day 1, 15, 29, 43, 71, 99, 127, 155, 183, 274 and 365 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)

  13. the safety 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 number, percentage and reporting period of adverse events of SYN023 compared to HyperRab® S/D



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:

  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 >=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 30 km of 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
  8. Has body mass index (BMI) between 18 and 36 (weight/height2) by nomogram

Exclusion Criteria:

  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 180 days before Study Day 1
  8. Planned participation in any other investigational study during the study period.
  9. Received systemic immunosuppressant medication not specified by the protocol
  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

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


Contacts
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Contact: Lisa Huang +886-2-87582587 Lisa.Huang@ppdi.com

Sponsors and Collaborators
Synermore Biologics Co., Ltd.

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Responsible Party: Synermore Biologics Co., Ltd.
ClinicalTrials.gov Identifier: NCT03961555     History of Changes
Other Study ID Numbers: SYN023-004
First Posted: May 23, 2019    Key Record Dates
Last Update Posted: May 23, 2019
Last Verified: May 2019
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
Vaccines
Immunoglobulins
Antibodies
gamma-Globulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs