Human Rabies
Conditions
Brief summary
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.
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.
Interventions
BIOLOGICALSYN023
The effects of SYN023 on immunogenicity of rabies vaccines Imovax and RabAvert will be compared to the effect of human rabies immune globulin.
BIOLOGICALImovax
Subjects will receive SYN023 or HyperRAB ST (human rabies immune globulin) and 5 doses of Imovax rabies vaccine
BIOLOGICALRabAvert
Subjects will receive SYN023 or HyperRAB ST (human rabies immune globulin) and 5 doses of RabAvert rabies vaccine
BIOLOGICALHyperRAB ST (human rabies immune globulin)
The effects of SYN023 on immunogenicity of rabies vaccines Imovax and RabAvert will be compared to the effect of human rabies immune globulin.
Sponsors
inVentiv Health Clinical
Synermore Biologics Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female subjects between 18 and 50 years of age, inclusive 2. Body mass index between 18 and 30 kg/m², inclusive 3. Female subjects physically capable of pregnancy (i.e., not sterilized and still menstruating or within 1 year of the last menses if menopausal) must: 1. Agree to avoid pregnancy from 28 days prior to Study Day 0 through the duration of the study. 2. 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. 4. Women of childbearing potential must have a negative serum pregnancy test within 24 hours preceding receipt of each dose. 5. 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
1. Oral temperature ≥37.5°C at screening 2. 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. 3. 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) 4. Abnormal PT (INR) PTT 5. Abnormal screening urinalysis result that is, per the investigator, clinically significant, or a screening urine dipstick result of ≥2+ protein 6. Positive screening urine test for illicit drugs (opiates, cocaine, amphetamines methamphetamines, barbiturates, benzodiazepines, tetrahydrocannabinol, PCP, MDMA, and methadone) 7. History or evidence of autoimmune disease 8. History or evidence of any past, present, or future possible immunodeficiency state, including laboratory evidence of human immunodeficiency virus (HIV) 1 or 2 infection 9. History or evidence of chronic hepatitis 10. History or evidence of rabies infection 11. 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 12. 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 13. History of non-compliance that, in the opinion of the investigator, will make it unlikely that the subject will comply with the protocol 14. Previous exposure to rabies vaccine 15. Receipt of an immunoglobulin or blood product within 90 days prior to Study Day 0 16. Receipt of immunosuppressive medications other than inhaled or topical immunosuppressant drugs within 45 days prior to Study Day 0 17. Body weight greater than 90 kg. 18. History or evidence of IgA deficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Serum Rabies Virus Neutralizing Activity | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Immunogenicity: Anti-CTB012 Antibodies Positive | 112 days | 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. |
| Percentage of Participants With Immunogenicity: Anti-CTB011 Antibodies Positive | 112 days | 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. |
| SYN023 Monoclonal Antibody Areas Under the Curve (AUC0-last, AUC0-inf) for CTB011 and CTB012) | 84 days | 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. |
| Percentage of Participants With Adverse Event Incidence of SYN023 Compared to HRIG in RabAvert and Imovax Reciptients | 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. |
| Maximum Serum Concentration Cmax | 84 days | 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. |
| Serum Clearance Rate (Clp) of CTB011 and CTB012 | 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. |
| Serum Half Lives of CTB011 and CTB012 | 84 days | 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. |
| Time to Maximum Concentration Tmax of CTB011 and CTB012 | 84 days | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Imovax, SYN023 Subjects will receive SYN023 and 5 doses of Imovax rabies vaccine
SYN023: The effects of SYN023 on immunogenicity of rabies vaccines Imovax and RabAvert will be compared to the effect of human rabies immune globulin.
Imovax, human rabies immune globulin: Subjects will receive HyperRAB ST (human rabies immune globulin) and 5 doses of Imovax rabies vaccine
RabAvert, human rabies immune globulin: Subjects will receive HyperRAB ST (human rabies immune globulin) and 5 doses of RabAvert rabies vaccine | 40 |
| Imovax, Human Rabies Immune Globulin Subjects will receive HyperRAB ST (human rabies immune globulin) and 5 doses of Imovax rabies vaccine
SYN023: The effects of SYN023 on immunogenicity of rabies vaccines Imovax and RabAvert will be compared to the effect of human rabies immune globulin.
Imovax, human rabies immune globulin: Subjects will receive HyperRAB ST (human rabies immune globulin) and 5 doses of Imovax rabies vaccine
RabAvert, human rabies immune globulin: Subjects will receive HyperRAB ST (human rabies immune globulin) and 5 doses of RabAvert rabies vaccine | 40 |
| RabAvert, SYN023 Subjects will receive SYN023 and 5 doses of RabAvert rabies vaccine
SYN023: The effects of SYN023 on immunogenicity of rabies vaccines Imovax and RabAvert will be compared to the effect of human rabies immune globulin.
Imovax, human rabies immune globulin: Subjects will receive HyperRAB ST (human rabies immune globulin) and 5 doses of Imovax rabies vaccine
RabAvert, human rabies immune globulin: Subjects will receive HyperRAB ST (human rabies immune globulin) and 5 doses of RabAvert rabies vaccine | 42 |
| RabAvert, Human Rabies Immune Globulin Subjects will receive HyperRAB ST (human rabies immune globulin) and 5 doses of RabAvert rabies vaccine
SYN023: The effects of SYN023 on immunogenicity of rabies vaccines Imovax and RabAvert will be compared to the effect of human rabies immune globulin.
Imovax, human rabies immune globulin: Subjects will receive HyperRAB ST (human rabies immune globulin) and 5 doses of Imovax rabies vaccine
RabAvert, human rabies immune globulin: Subjects will receive HyperRAB ST (human rabies immune globulin) and 5 doses of RabAvert rabies vaccine | 42 |
| Total | 164 |
Baseline characteristics
| Characteristic | Imovax, SYN023 | Imovax, Human Rabies Immune Globulin | RabAvert, SYN023 | RabAvert, Human Rabies Immune Globulin | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants | 40 Participants | 42 Participants | 42 Participants | 164 Participants |
| BMI | 24.41 kg/m^2 STANDARD_DEVIATION 2.87 | 25.74 kg/m^2 STANDARD_DEVIATION 2.96 | 24.92 kg/m^2 STANDARD_DEVIATION 2.66 | 24.39 kg/m^2 STANDARD_DEVIATION 3.14 | 24.86 kg/m^2 STANDARD_DEVIATION 2.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 37 Participants | 37 Participants | 39 Participants | 40 Participants | 153 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 40 participants | 40 participants | 42 participants | 42 participants | 164 participants |
| Sex: Female, Male Female | 28 Participants | 27 Participants | 28 Participants | 20 Participants | 103 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 14 Participants | 22 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 42 | 0 / 40 | 0 / 42 |
| other Total, other adverse events | 20 / 40 | 25 / 42 | 24 / 40 | 31 / 42 |
| serious Total, serious adverse events | 0 / 40 | 0 / 42 | 0 / 40 | 1 / 42 |
Outcome results
Primary
Percentage of Participants With Serum Rabies Virus Neutralizing Activity
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).
Time frame: 112 days
Population: Per-Protocol Population (subject with complete RVNA data).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imovax, SYN023 | Percentage of Participants With Serum Rabies Virus Neutralizing Activity | 94.3 percentage of participants |
| Imovax, Human Rabies Immune Globulin | Percentage of Participants With Serum Rabies Virus Neutralizing Activity | 97.1 percentage of participants |
| RabAvert, SYN023 | Percentage of Participants With Serum Rabies Virus Neutralizing Activity | 97.1 percentage of participants |
| RabAvert, Human Rabies Immune Globulin | Percentage of Participants With Serum Rabies Virus Neutralizing Activity | 100 percentage of participants |
p-value: 0.4187ANOVA
Secondary
Maximum Serum Concentration Cmax
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.
Time frame: 84 days
Population: Per-Protocol Population (subjects who received all scheduled doses of a study treatment and remained on study for at least 28 days without major protocol violation). No detectable and quantifiable levels of CTB011 and CTB012 were observed in human rabies immune globulin groups, so no PK or statistical analysis was planned.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Imovax, SYN023 | Maximum Serum Concentration Cmax | Cmax for CTB-011 | 686 ng/mL | Standard Deviation 292 |
| Imovax, SYN023 | Maximum Serum Concentration Cmax | Cmax for CTB-012 | 959 ng/mL | Standard Deviation 449 |
| Imovax, Human Rabies Immune Globulin | Maximum Serum Concentration Cmax | Cmax for CTB-011 | 610 ng/mL | Standard Deviation 240 |
| Imovax, Human Rabies Immune Globulin | Maximum Serum Concentration Cmax | Cmax for CTB-012 | 879 ng/mL | Standard Deviation 400 |
Secondary
Percentage of Participants With Adverse Event Incidence of SYN023 Compared to HRIG in RabAvert and Imovax Reciptients
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.
Time frame: 42 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Imovax, SYN023 | Percentage of Participants With Adverse Event Incidence of SYN023 Compared to HRIG in RabAvert and Imovax Reciptients | Unsolicited AEs | 60 percentage of participants |
| Imovax, SYN023 | Percentage of Participants With Adverse Event Incidence of SYN023 Compared to HRIG in RabAvert and Imovax Reciptients | Solicited AEs | 15 percentage of participants |
| Imovax, Human Rabies Immune Globulin | Percentage of Participants With Adverse Event Incidence of SYN023 Compared to HRIG in RabAvert and Imovax Reciptients | Solicited AEs | 47.5 percentage of participants |
| Imovax, Human Rabies Immune Globulin | Percentage of Participants With Adverse Event Incidence of SYN023 Compared to HRIG in RabAvert and Imovax Reciptients | Unsolicited AEs | 50 percentage of participants |
| RabAvert, SYN023 | Percentage of Participants With Adverse Event Incidence of SYN023 Compared to HRIG in RabAvert and Imovax Reciptients | Unsolicited AEs | 73.8 percentage of participants |
| RabAvert, SYN023 | Percentage of Participants With Adverse Event Incidence of SYN023 Compared to HRIG in RabAvert and Imovax Reciptients | Solicited AEs | 28.6 percentage of participants |
| RabAvert, Human Rabies Immune Globulin | Percentage of Participants With Adverse Event Incidence of SYN023 Compared to HRIG in RabAvert and Imovax Reciptients | Unsolicited AEs | 59.5 percentage of participants |
| RabAvert, Human Rabies Immune Globulin | Percentage of Participants With Adverse Event Incidence of SYN023 Compared to HRIG in RabAvert and Imovax Reciptients | Solicited AEs | 40.5 percentage of participants |
Secondary
Percentage of Participants With Immunogenicity: Anti-CTB011 Antibodies Positive
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.
Time frame: 112 days
Population: Subjects at least 1 initial anti-SYN023 assay results
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imovax, SYN023 | Percentage of Participants With Immunogenicity: Anti-CTB011 Antibodies Positive | 36.8 percentage of subjects |
| Imovax, Human Rabies Immune Globulin | Percentage of Participants With Immunogenicity: Anti-CTB011 Antibodies Positive | 28.6 percentage of subjects |
| RabAvert, SYN023 | Percentage of Participants With Immunogenicity: Anti-CTB011 Antibodies Positive | 31.4 percentage of subjects |
| RabAvert, Human Rabies Immune Globulin | Percentage of Participants With Immunogenicity: Anti-CTB011 Antibodies Positive | 21.4 percentage of subjects |
Secondary
Percentage of Participants With Immunogenicity: Anti-CTB012 Antibodies Positive
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.
Time frame: 112 days
Population: Subjects at least 1 initial anti-SYN023 assay results
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imovax, SYN023 | Percentage of Participants With Immunogenicity: Anti-CTB012 Antibodies Positive | 5.3 percentage of participants |
| Imovax, Human Rabies Immune Globulin | Percentage of Participants With Immunogenicity: Anti-CTB012 Antibodies Positive | 0 percentage of participants |
| RabAvert, SYN023 | Percentage of Participants With Immunogenicity: Anti-CTB012 Antibodies Positive | 0 percentage of participants |
| RabAvert, Human Rabies Immune Globulin | Percentage of Participants With Immunogenicity: Anti-CTB012 Antibodies Positive | 3.6 percentage of participants |
Secondary
Serum Clearance Rate (Clp) of CTB011 and CTB012
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.
Time frame: 84 days
Population: Per-Protocol Population (subjects who received all scheduled doses of a study treatment and remained on study for at least 28 days without major protocol violation). No detectable and quantifiable levels of CTB011 and CTB012 were observed in human rabies immune globulin groups, so no PK or statistical analysis was planned.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Imovax, SYN023 | Serum Clearance Rate (Clp) of CTB011 and CTB012 | clearance rates for CTB011 | 1.18 L/day | Standard Deviation 0.62 |
| Imovax, SYN023 | Serum Clearance Rate (Clp) of CTB011 and CTB012 | clearance rates for CTB012 | 0.74 L/day | Standard Deviation 0.29 |
| Imovax, Human Rabies Immune Globulin | Serum Clearance Rate (Clp) of CTB011 and CTB012 | clearance rates for CTB011 | 1.14 L/day | Standard Deviation 0.59 |
| Imovax, Human Rabies Immune Globulin | Serum Clearance Rate (Clp) of CTB011 and CTB012 | clearance rates for CTB012 | 0.77 L/day | Standard Deviation 0.46 |
Secondary
Serum Half Lives of CTB011 and CTB012
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.
Time frame: 84 days
Population: Per-Protocol Population (subjects who received all scheduled doses of a study treatment and remained on study for at least 28 days without major protocol violation). No detectable and quantifiable levels of CTB011 and CTB012 were observed in human rabies immune globulin groups, so no PK or statistical analysis was planned.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Imovax, SYN023 | Serum Half Lives of CTB011 and CTB012 | t1/2 for CTB-011 | 19.19 day | Standard Deviation 6.64 |
| Imovax, SYN023 | Serum Half Lives of CTB011 and CTB012 | t1/2 for CTB-012 | 20.76 day | Standard Deviation 8.73 |
| Imovax, Human Rabies Immune Globulin | Serum Half Lives of CTB011 and CTB012 | t1/2 for CTB-011 | 22.12 day | Standard Deviation 5.18 |
| Imovax, Human Rabies Immune Globulin | Serum Half Lives of CTB011 and CTB012 | t1/2 for CTB-012 | 22.86 day | Standard Deviation 8.7 |
Secondary
SYN023 Monoclonal Antibody Areas Under the Curve (AUC0-last, AUC0-inf) for CTB011 and CTB012)
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.
Time frame: 84 days
Population: Per-Protocol Population (subjects who received all scheduled doses of a study treatment and remained on study for at least 28 days without major protocol violation)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Imovax, SYN023 | SYN023 Monoclonal Antibody Areas Under the Curve (AUC0-last, AUC0-inf) for CTB011 and CTB012) | AUC0-inf for CTB-011 | 20604.56 day*ng/mL | Standard Deviation 8904.6 |
| Imovax, SYN023 | SYN023 Monoclonal Antibody Areas Under the Curve (AUC0-last, AUC0-inf) for CTB011 and CTB012) | AUC0-t for CTB-011 | 17549.49 day*ng/mL | Standard Deviation 8300.05 |
| Imovax, SYN023 | SYN023 Monoclonal Antibody Areas Under the Curve (AUC0-last, AUC0-inf) for CTB011 and CTB012) | AUC0-t for CTB-012 | 22896.71 day*ng/mL | Standard Deviation 113653.68 |
| Imovax, SYN023 | SYN023 Monoclonal Antibody Areas Under the Curve (AUC0-last, AUC0-inf) for CTB011 and CTB012) | AUC0-inf for CTB-012 | 30943.29 day*ng/mL | Standard Deviation 11230.39 |
| Imovax, Human Rabies Immune Globulin | SYN023 Monoclonal Antibody Areas Under the Curve (AUC0-last, AUC0-inf) for CTB011 and CTB012) | AUC0-inf for CTB-012 | 32495.98 day*ng/mL | Standard Deviation 11892.98 |
| Imovax, Human Rabies Immune Globulin | SYN023 Monoclonal Antibody Areas Under the Curve (AUC0-last, AUC0-inf) for CTB011 and CTB012) | AUC0-t for CTB-011 | 17318.95 day*ng/mL | Standard Deviation 7488.84 |
| Imovax, Human Rabies Immune Globulin | SYN023 Monoclonal Antibody Areas Under the Curve (AUC0-last, AUC0-inf) for CTB011 and CTB012) | AUC0-inf for CTB-011 | 20924.6 day*ng/mL | Standard Deviation 7041.56 |
| Imovax, Human Rabies Immune Globulin | SYN023 Monoclonal Antibody Areas Under the Curve (AUC0-last, AUC0-inf) for CTB011 and CTB012) | AUC0-t for CTB-012 | 23617.93 day*ng/mL | Standard Deviation 10768.7 |
Secondary
Time to Maximum Concentration Tmax of CTB011 and CTB012
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.
Time frame: 84 days
Population: Per-Protocol Population (subjects who received all scheduled doses of a study treatment and remained on study for at least 28 days without major protocol violation). No detectable and quantifiable levels of CTB011 and CTB012 were observed in human rabies immune globulin groups, so no PK or statistical analysis was planned.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Imovax, SYN023 | Time to Maximum Concentration Tmax of CTB011 and CTB012 | Tmax for CTB-012 | 6.892 day | Standard Deviation 6.316 |
| Imovax, SYN023 | Time to Maximum Concentration Tmax of CTB011 and CTB012 | Tmax for CTB-011 | 6.655 day | Standard Deviation 5.957 |
| Imovax, Human Rabies Immune Globulin | Time to Maximum Concentration Tmax of CTB011 and CTB012 | Tmax for CTB-012 | 6.932 day | Standard Deviation 4.417 |
| Imovax, Human Rabies Immune Globulin | Time to Maximum Concentration Tmax of CTB011 and CTB012 | Tmax for CTB-011 | 6.686 day | Standard Deviation 4.741 |