- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02956746
A Comparison of the Safety, PD and PK of a Single Dose of SYN023 Administered With Licensed Rabies Vaccines (RabiesMab)
February 1, 2019 updated by: Synermore Biologics Co., Ltd.
A Phase 2 Randomized Blinded Placebo Controlled Comparison of the Safety Pharmacokinetics and Pharmacodynamics of a Single Dose of SYN023 Administered With Licensed Rabies Vaccines in Healthy Adult Subjects
This is single site, randomized, blinded comparison of the immunogenicity, of Imovax (RVi) and Rabavert (RVa) rabies vaccines when subjects are administered rabies immune globulin (RIG) or SYN023.
Subjects will be randomized into one of four dose groups: RVi + SYN023, RVi+RIG, RVa+SYN023 and RVa+RIG.
The initial dose of RVi and RVa will be co-administered with either RIG or SYN023).
Rabies virus neutralizing activity (RVNA) and blood levels of SYN023 will be measured for the remainder of the trial while the rest of the five RVi and RVa doses are given.
The study will last 112 days.
SYN023 concentrations and anti-SYN023 antibodies will also be measured.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Administered immunoglobulins directed against vaccine antigens have the potential to inhibit the immune response to a vaccine.
Both vaccination and immune globulin are used together in the post exposure prophylaxis of rabies virus infection.
SYN023 (a mixture of two monoclonal antibodies CTB011 and CTB012) may be used instead of human rabies immune globulin.
Since there is a risk of antagonism of vaccine induced immunity by SYN023, as there is with rabies immune globulin, it is necessary to study possible interactions of these two agents that might be used concurrently.
This is single site, randomized, blinded comparison of the immunogenicity, of Imovax (RVi) and Rabavert (RVa) rabies vaccines when administered concurrently with rabies immune globulin (RIG) or SYN023.
Subjects will be randomized into one of four dose groups: RVi + SYN023, RVi + RIG, RVa+SYN023 and RVa + RIG.
The initial dose of RVi and RVa will be co-administered with either RIG or SYN023).
The remaining 4 doses of RVi and RVa will be administered intramuscularly as specified in the product labeling.
Serum rabies virus neutralizing activity (RVNA) and serum concentrations of the components of of SYN023 will be measured for the remainder of the trial while the rest of the five RVi and RVa doses are given.
Adverse events will be collected for the duration of the trial.
The study will last 112 days.
Anti-SYN023 antibodies will also be measured.
Study Type
Interventional
Enrollment (Actual)
164
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Florida
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Miami, Florida, United States, 33136
- inVentiv Clinical Research Facility, 1951 NW 7th Ave. Suit 450
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 50 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male or female subjects between 18 and 50 years of age, inclusive
- Body mass index between 18 and 30 kg/m², inclusive
Female subjects physically capable of pregnancy (i.e., not sterilized and still menstruating or within 1 year of the last menses if menopausal) must:
- Agree to avoid pregnancy from 28 days prior to Study Day 0 through the duration of the study.
- If in a sexual relationship with a man, use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include: the use of at least two forms of contraception, including use by a partner of a barrier method (e.g., male condom with intravaginal spermicide) as one form of contraception.
- Women of childbearing potential must have a negative serum pregnancy test within 24 hours preceding receipt of each dose.
- Can understand and sign the informed consent document, can communicate with the investigator and provide updated contact information as needed for the duration of the study, has no current plans to move from the study area for the duration of the study, and can understand and comply with the requirements of the protocol.
Exclusion Criteria:
- Oral temperature ≥37.5°C at screening
- Complete blood count (CBC) and platelet count abnormal values (>5% above the upper limit of normal [ULN] or >5% below the lower limit of normal [LLN] per local laboratory parameters) at screening with exception of absolute lymphocyte count.
- Abnormally elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, alkaline phosphatase (ALP), or creatinine (Cr) values at screening (however a single test AST, ALT or ALP may be >10% above the ULN per local laboratory parameters)
- Abnormal PT (INR) PTT
- Abnormal screening urinalysis result that is, per the investigator, clinically significant, or a screening urine dipstick result of ≥2+ protein
- Positive screening urine test for illicit drugs (opiates, cocaine, amphetamines methamphetamines, barbiturates, benzodiazepines, tetrahydrocannabinol, PCP, MDMA, and methadone)
- History or evidence of autoimmune disease
- History or evidence of any past, present, or future possible immunodeficiency state, including laboratory evidence of human immunodeficiency virus (HIV) 1 or 2 infection
- History or evidence of chronic hepatitis
- History or evidence of rabies infection
- History or evidence of any other acute or chronic disease that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of the drug or compromise the safety of the subject; for example a clinically relevant history of respiratory, thyroid, gastrointestinal, renal, hepatic, hematological, lymphatic, oncologic, cardiovascular, psychiatric, neurological, musculoskeletal, genitourinary, infective, inflammatory, immunological, dermatological or connective tissue disease
- History or evidence of allergic disease or reaction, including adverse responses to therapeutic monoclonal antibodies that, in the opinion of the investigator, may compromise the safety of the subject
- History of non-compliance that, in the opinion of the investigator, will make it unlikely that the subject will comply with the protocol
- Previous exposure to rabies vaccine
- Receipt of an immunoglobulin or blood product within 90 days prior to Study Day 0
- Receipt of immunosuppressive medications other than inhaled or topical immunosuppressant drugs within 45 days prior to Study Day 0
- Body weight greater than 90 kg.
- History or evidence of IgA deficiency
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Imovax, SYN023
Subjects will receive SYN023 and 5 doses of Imovax rabies vaccine
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The effects of SYN023 on immunogenicity of rabies vaccines Imovax and RabAvert will be compared to the effect of human rabies immune globulin.
Subjects will receive SYN023 or HyperRAB ST (human rabies immune globulin) and 5 doses of Imovax rabies vaccine
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Active Comparator: Imovax, human rabies immune globulin
Subjects will receive HyperRAB ST (human rabies immune globulin) and 5 doses of Imovax rabies vaccine
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Subjects will receive SYN023 or HyperRAB ST (human rabies immune globulin) and 5 doses of Imovax rabies vaccine
The effects of SYN023 on immunogenicity of rabies vaccines Imovax and RabAvert will be compared to the effect of human rabies immune globulin.
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Experimental: RabAvert, SYN023
Subjects will receive SYN023 and 5 doses of RabAvert rabies vaccine
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The effects of SYN023 on immunogenicity of rabies vaccines Imovax and RabAvert will be compared to the effect of human rabies immune globulin.
Subjects will receive SYN023 or HyperRAB ST (human rabies immune globulin) and 5 doses of RabAvert rabies vaccine
|
Active Comparator: RabAvert, human rabies immune globulin
Subjects will receive HyperRAB ST (human rabies immune globulin) and 5 doses of RabAvert rabies vaccine
|
The effects of SYN023 on immunogenicity of rabies vaccines Imovax and RabAvert will be compared to the effect of human rabies immune globulin.
Subjects will receive SYN023 or HyperRAB ST (human rabies immune globulin) and 5 doses of RabAvert rabies vaccine
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Serum Rabies Virus Neutralizing Activity
Time Frame: 112 days
|
Inhibitory activity of serum in standard rabies virus inhibition test (RFFIT: Rapid Fluorescent Foci Inhibition Test) assessed as serum RVNA ≥ 0.5 IU/mL.
RFFIT is a serum neutralization (inhibition) test, which means it measures the ability of rabies specific antibodies to neutralize rabies virus and prevent the virus from infecting cells.
These antibodies are called rabies virus neutralizing antibodies (RVNA).
|
112 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Adverse Event Incidence of SYN023 Compared to HRIG in RabAvert and Imovax Reciptients
Time Frame: 42 days
|
Electrocardiograms are performed to monitor subject safety.
Laboratory evaluations for subject safety (adverse events) are serum chemistry evaluations, blood urea nitrogen, creatinine, bilirubin, alanine amino transferase, aspartate amino transferase, creatine phosphokinase, troponin, potassium, sodium, bicarbonate, calcium, complete blood count, platelet count, differential count, PT(prothrombin time, international normalized ratio) and PTT (partial prothrombin time and urinalyses for monitoring of safety.
Additional laboratory tests may be required for evaluation of specific adverse events such as anaphylaxis and immune complex diseases.
Adverse events and serious adverse events will be analyzed.
A comparison of adverse event incidence between the four treatment groups will be performed.
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42 days
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Percentage of Participants With Immunogenicity: Anti-CTB012 Antibodies Positive
Time Frame: 112 days
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Measurement of the development of anti-CTB012 antibodies (a component of anti-SYN023 antibodies) in participants which will be analyzed on a continuous scale as a categorical variable by treatment assignment, with descriptive statistics.
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112 days
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Percentage of Participants With Immunogenicity: Anti-CTB011 Antibodies Positive
Time Frame: 112 days
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Measurement of the development of anti-CTB011 antibodies (a component of anti-SYN023 antibodies) in participants which will be analyzed on a continuous scale as a categorical variable by treatment assignment, with descriptive statistics.
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112 days
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SYN023 Monoclonal Antibody Areas Under the Curve (AUC0-last, AUC0-inf) for CTB011 and CTB012)
Time Frame: 84 days
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The area under the time concentration curve for SYN023 mAb components CTB011 and CTB012 will be estimated at Day 0 ( pre-dose), Day 1, Day 3, Day 7, Day 14, Day 28, Day 35, Day 42, and Day 84 post-dose, using non compartmental analysis.
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84 days
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Time to Maximum Concentration Tmax of CTB011 and CTB012
Time Frame: 84 days
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Interval from time 0 to maximum measured concentration of CTB011 and CTB012 (SYN023 components) at Day 0 ( pre-dose), Day 1, Day 3, Day 7, Day 14, Day 28, Day 35, Day 42, and Day 84 post-dose, using non compartmental analysis.
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84 days
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Maximum Serum Concentration Cmax
Time Frame: 84 days
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Maximum concentration of of CTB011 and CTB012 at Day 0 ( pre-dose), Day 1, Day 3, Day 7, Day 14, Day 28, Day 35, Day 42, and Day 84 post-dose, using non compartmental analysis.
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84 days
|
Serum Clearance Rate (Clp) of CTB011 and CTB012
Time Frame: 84 days
|
Calculated serum clearance rates for CTB011 and CTB012 at Day 0 ( pre-dose), Day 1, Day 3, Day 7, Day 14, Day 28, Day 35, Day 42, and Day 84 post-dose, using non compartmental analysis.
|
84 days
|
Serum Half Lives of CTB011 and CTB012
Time Frame: 84 days
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The time in hours to reduce the serum concnetration of CTB011 and CTB012 to 50% of the maximum serum concentration at Day 0 ( pre-dose), Day 1, Day 3, Day 7, Day 14, Day 28, Day 35, Day 42, and Day 84 post-dose, using non compartmental analysis.
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84 days
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Wyatt J David, PhD, inVentiv Health Clinical Research Services LLC
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 1, 2016
Primary Completion (Actual)
December 1, 2017
Study Completion (Actual)
January 1, 2018
Study Registration Dates
First Submitted
November 1, 2016
First Submitted That Met QC Criteria
November 3, 2016
First Posted (Estimate)
November 6, 2016
Study Record Updates
Last Update Posted (Actual)
February 27, 2019
Last Update Submitted That Met QC Criteria
February 1, 2019
Last Verified
February 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SYN023-002
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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