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Submitted by: Ms. Fatima Aquino 2019-09-17 12:55:16 Last Updated by: Principe, Jeverly Ann S 2019-09-30 14:56:56


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

PHRR190927-002197

SYN023-004

2019-CT0494

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

This is a Phase 2b, double blinded, randomized study of SYN023 compared to HyperRab® S/D (a licensed HRIG) for PEP of patients who have been confirmed to have met all inclusion/exclusion criteria for their treatment group. The desired indication is the prevention of rabies as part of PEP. The trial will be conducted in least two countries where rabies occurs. The trial will enroll sequentially two different risk substrata of WHO Category 3 rabies exposure. 

Regime Classification Priority
2017 - 2022 Responsive health systems Access to essential medical products, vaccines and technologies
Start Date Duration in Months Target Completion Date Actual Completion Date
2019-08-30 12 2020-08-30 0000-00-00

Ongoing

Institution Classification Region LTO #
Synermore Biologics Co., Ltd. Private Business Taiwan N/A
Institution Classification Region LTO #
PPD Pharmaceutical Development Philippines Corporation Private Business NCR 3000002863828
Institution Region
Synermore Biologics Co., Ltd. Taiwan
Name E-Mail Institution and Institution Address
Glenda Lorraine Monsanto GlendaLorraine.Monsanto@ppdi.com 22/F Net Park Bldg, 5th Ave. E-Square, Crescent Park West Bonifacio Global City Taguig, Philippines, 1630
Name E-Mail Institution and Institution Address
Rizza Beth Co RizzaBeth.Co@ppdi.com 22/F Net Park Bldg, 5th Ave. E-Square, Crescent Park West Bonifacio Global City Taguig, Philippines, 1630
Name Expertise Affiliation
Beatriz P. Quiambao, MD Principal Investigator Research Institute for Tropical Medicine
Camilo C. Roa Jr., MD Principal Investigator Manila Doctors Hospital
Loreta Baldovino Zoleta-de Jesus, MD Principal Investigator De La Salle Angelo King Medical Research Center
Mari Rose A. Delos Reyes, MD Principal Investigator Research Institute for Tropical Medicine
Maria Rosario Z. Capeding, MD Principal Investigator Asian Hospital and Medical Center
May Emmeline Montellano, MD Principal Investigator Far Eastern University - Nicanor Reyes Memorial Foundation Hospital
Remigio Olveda, MD Principal Investigator Center of Excellence in Drug Research, Evaluation and Studies, Inc.
Ronald Allan R. Payumo, MD Principal Investigator Mary Johnston Hospital
Project Location Institutional Ethics Review Board
Research Institute for Tropical Medicine Research Institute for Tropical Medicine Institutional Review Board
Manila Doctors Hospital Manila Doctors Hospital Institutional Review Board
De La Salle Angelo King Medical Research Center N/A
Research Institute for Tropical Medicine Research Institute for Tropical Medicine Institutional Review Board
Asian Hospital and Medical Center Asian Hospital and Medical Center Institutional Review Board
Far Eastern University - Nicanor Reyes Memorial Foundation Hospital Far Eastern University - Nicanor Reyes Memorial Foundation Hospital Ethics Review Committee
Center of Excellence in Drug Research, Evaluation and Studies, Inc. N/A
Mary Johnston Hospital Mary Johnston Hospital Ethics & Review Committee

Rabies Virus

  • 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

AND

  • 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

AND

  • 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

AND

  • There are no probable or confirmed cases of rabies in SYN023 recipients.

  • To demonstrate that the geometric mean RVNA concentration for SYN023 is superior to the geometric mean RVNA concentration for HRIG on Study Day 4
  • To demonstrate that the geometric mean RVNA AUEC1-15 for SYN023 is superior to the geometric mean RVNA AUEC1-15 for HRIG
  • 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.
  • 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.
  • To describe the pharmacokinetics of SYN023 using non‑compartmental analysis. Vd, Cmax, Tmax, AUC1-t, AUC1-inf, t½, Cl, and λz will be calculated when possible in the LRG and NRG protocol and as treated populations.
  • To evaluate presence and effects of anti-SYN023 antibodies (anti-CTB011, anti-CTB012)
  • To evaluate the safety of SYN023 compared to HyperRab® S/D
  • To describe any effect of increasing BMI on SYN023 and RVNA concentrations.

Recruiting

  • Philippines
  • Thailand
  • United States

Clinical Trial

SYN023-004

20190315132234

2019-07-03

0000-00-00

448

Unspecified

Unspecified

30 Aug 2019

Low Risk Group (LRG) Inclusion Criteria

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 
  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 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

Normal Risk Group (NRG) Inclusion Criteria

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 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 LRG and NRG

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)

Interventional

SYN023

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. CTB012 possesses a slightly broader spectrum of activity than CTB011.  Both monoclonal antibodies bind to non-overlapping epitopes thus single point mutations should not escape binding by at least one Mab.  The combined mixture SYN023 demonstrated medium to high neutralizing activity against most of the strains evaluated. These results were verified from two different laboratories.

After thorough wound sanitation, injections of the entire calculated dose of SYN023 should be administered into and around all the bite wounds on Study Day 1. The dose of SYN023 should be calculated based on body weight: 0.3 mg/kg.  For example, a 70 kg person has a calculated dose of 21 mg.  The entire calculated dose should be given.  Doses up to 3 mL may be given at a single injection site. Care must be taken NOT to administer a rabies vaccine near the Study Drug administration site. 

 

Date Amendment Classification Reason
2019-08-28 Amendments related to the protocol Additional dose of rabies vaccine

Randomized

Double Blind

Unspecified

Single

To provide a robust supply chain to avoid deaths from unavailability.

Phase II

Utilization Utilization Info
Publication

The final study report will be made available to the principal investigator(s) for purposes of publications.  The principal investigator and study staff must send all manuscripts, abstracts, and presentations using data from this study to the sponsor for review prior to their submission.  The sponsor reserves the right to delete any part or parts of such materials deemed to be confidential or proprietary.  From the sponsor.  All changes to the protocol must be submitted to the IRB/IEC and must be approved by the IRB/IEC unless they are administrative changes, typographical errors or required for subject safety prior to their implementation.  This is the third version of the protocol.

Oral Presentation
Drug Literature
Posters
Others
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