Efficacy of the New CPRV
Conditions
Keywords
CPRV, SPEEDA, intradermal, pre-exposure, booster
Brief summary
Pre exposure rabies vaccination with a new Chromatographically Purified Vero-cell Rabies Vaccine(SPEEDA) is as effective as Purified Vero-cell Rabies vaccine. After the pre exposure rabies vaccination with a new Chromatographically Purified Vero-cell Rabies Vaccine(SPEEDA), the Rabies neutralizing antibodies in all patients on day 42 are 0.5 IU/ml or more. And Simulated post-exposure rabies booster vaccination with a new Chromatographically Purified Vero-cell Rabies Vaccine(SPEEDA) is as effective as Purified Vero-cell Rabies vaccine. After the simulated post-exposure rabies booster vaccination with a new Chromatographically Purified Vero-cell Rabies Vaccine(SPEEDA), the Rabies neutralizing antibodies in all patients on day 14 after the booster are 0.5 IU/ml or more.
Detailed description
Pre-exposure vaccination will be done according to standard protocol. Participants will be injected with one dose on day 0, 7 and 28. Blood samples will be taken on day 0, 28 and 42 after the first vaccination dose. 360 days later, participants will receive simulated post-exposure rabies booster vaccination one dose on day 0 and 3. Blood samples will be taken again on day 0(360 days) and 14(374 days) after the booster vaccination. Rabies neutralizing antibody levels will be measured by Rapid Fluorescent Focus Inhibition Test(RFFIT). And the levels of 0.5 IU/ml or more is considered acceptable protective level. For statistical analysis, percentage of subjects achieving seroconversion (defined as RNab ≥ 0.5 IU/ mL) are determine at each sampling time. The average of the titer used in this study is Geometric mean titer(GMT). 95 percent confidence interval(95% CI) of the GMT will be calculated for each study group from individual measurements of serum rabies antibody levels at each sampling time. One-way ANOVA would be used to calculated the significance of the difference between the GMT of three groups, SPEEDA® intradermal injection, SPEEDA® intramuscular injection and PVRV intramuscular injection. The primary criterion for this comparison are the rabies antibody value on day 42 (2 weeks after the third vaccine dose of pre-exposure vaccination) and on day 374(2 weeks after the first vaccine dose of booster vaccination). Results will be deemed statistically significant at p \< 0.05. Safety data (immediate, local and systemic reactions) were summarized as numbers and percentages.
Interventions
BIOLOGICALNew Chromatographically Purified Vero-cell Rabies vaccine(new CPRV).
new CPRV 0.1 ml intradermal route and 0.5 ml intramuscular route are the experimental intervention
Sponsors
Queen Saovabha Memorial Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy * Can visit according to the protocol
Exclusion criteria
* Fever * Acute illness * History of rabies vaccination * Allergic to the vaccines' component * Immunosuppressive conditions such as HIV infection, transplantation, chronic renal failure, received steroid or immunosuppressive drugs and anti-malarial drugs within previous two months or any blood products within previous three months * Female participant must not be pregnant * All female participant must have urine pregnancy test negative prior to participate the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT) | on day 0 | Blood samples will be drawn on day 0(After the first injection). The samples will be centrifuged and kept as serum under - 20 degree Celsius. The serum will be test by Rapid Florescent Focus Inhibition Test. Rabies neutralizing antibody levels will be determined and expressed in international units per mL. Percentage of Subjects achieving seroconversion (defined as RNab ≥ 0.5 IU/ mL) are determine at each sampling time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Side Effects of the Vaccines. These Include Pain, Swelling, Redness, Myalgia, Rash, Fever. Serious Adverse Events Will Also be Recorded. | up to 7 days after each injection | There are five injections, on day 0, 7, 28, 360 and 363. The side effects will be record in number and percentage. |
Countries
Thailand
Participant flow
Recruitment details
We recruited 66 subjects from Faculty of Veterinarian, Chulalongkorn University. The recruitment held between June 25, 2012 and July 2, 2012. Others 39 subjects was recruited from Faculty of Veterinarian, Mahanakorn University of Technology.
Participants by arm
| Arm | Count |
|---|---|
| PrEP and Simulated PEP With PVRV by Intramuscular Route New Chromatographically Purified Vero-cell Rabies vaccine(new CPRV).: new CPRV 0.1 ml intradermal route and 0.5 ml intramuscular route are the experimental intervention | 28 |
| PrEP and Simulated PEP With New CPRV by Intramuscular Route New Chromatographically Purified Vero-cell Rabies vaccine(new CPRV).: new CPRV 0.1 ml intradermal route and 0.5 ml intramuscular route are the experimental intervention | 27 |
| PrEP and Simulated PEP With New CPRV by Intradermal Route New Chromatographically Purified Vero-cell Rabies vaccine(new CPRV).: new CPRV 0.1 ml intradermal route and 0.5 ml intramuscular route are the experimental intervention | 26 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 3 | 6 |
| Overall Study | Preexisting rabies antibody | 3 | 4 | 3 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | PrEP and Simulated PEP With PVRV by Intramuscular Route | PrEP and Simulated PEP With New CPRV by Intramuscular Route | PrEP and Simulated PEP With New CPRV by Intradermal Route | Total |
|---|---|---|---|---|
| Age, Continuous | 18.96 years STANDARD_DEVIATION 1.138 | 20.04 years STANDARD_DEVIATION 5.633 | 18.92 years STANDARD_DEVIATION 0.744 | 19.31 years STANDARD_DEVIATION 3.345 |
| Region of Enrollment Thailand | 28 participants | 27 participants | 26 participants | 81 participants |
| Sex: Female, Male Female | 22 Participants | 18 Participants | 19 Participants | 59 Participants |
| Sex: Female, Male Male | 6 Participants | 9 Participants | 7 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 35 / 35 | 35 / 35 | 35 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 35 | 0 / 35 |
Outcome results
Primary
Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT)
Blood samples will be drawn on day 0(After the first injection). The samples will be centrifuged and kept as serum under - 20 degree Celsius. The serum will be test by Rapid Florescent Focus Inhibition Test. Rabies neutralizing antibody levels will be determined and expressed in international units per mL. Percentage of Subjects achieving seroconversion (defined as RNab ≥ 0.5 IU/ mL) are determine at each sampling time.
Time frame: on day 0
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| PrEP and Simulated PEP With PVRV by Intramuscular Route | Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT) | 0 International unit per ml |
| PrEP and Simulated PEP With New CPRV by Intramuscular Route | Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT) | 0 International unit per ml |
| PrEP and Simulated PEP With New CPRV by Intradermal Route | Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT) | 0 International unit per ml |
Primary
Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT)
Blood samples will be drawn on day 28(After the first injection). The samples will be centrifuged and kept as serum under - 20 degree Celsius. The serum will be test by Rapid Florescent Focus Inhibition Test. Rabies neutralizing antibody levels will be determined and expressed in international units per mL. Percentage of Subjects achieving seroconversion (defined as RNab ≥ 0.5 IU/ mL) are determine at each sampling time.
Time frame: on day 28
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| PrEP and Simulated PEP With PVRV by Intramuscular Route | Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT) | 2.67 International unit per ml |
| PrEP and Simulated PEP With New CPRV by Intramuscular Route | Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT) | 4.23 International unit per ml |
| PrEP and Simulated PEP With New CPRV by Intradermal Route | Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT) | 1.83 International unit per ml |
Primary
Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT)
Blood samples will be drawn on day 42(After the first injection). The samples will be centrifuged and kept as serum under - 20 degree Celsius. The serum will be test by Rapid Florescent Focus Inhibition Test. Rabies neutralizing antibody levels will be determined and expressed in international units per mL. Percentage of Subjects achieving seroconversion (defined as RNab ≥ 0.5 IU/ mL) are determine at each sampling time.
Time frame: on day 42
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| PrEP and Simulated PEP With PVRV by Intramuscular Route | Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT) | 11.49 International unit per ml |
| PrEP and Simulated PEP With New CPRV by Intramuscular Route | Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT) | 14.23 International unit per ml |
| PrEP and Simulated PEP With New CPRV by Intradermal Route | Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT) | 5.02 International unit per ml |
Primary
Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT)
Blood samples will be drawn on day 360(After the first injection). The samples will be centrifuged and kept as serum under - 20 degree Celsius. The serum will be test by Rapid Florescent Focus Inhibition Test. Rabies neutralizing antibody levels will be determined and expressed in international units per mL. Percentage of Subjects achieving seroconversion (defined as RNab ≥ 0.5 IU/ mL) are determine at each sampling time.
Time frame: on day 360
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| PrEP and Simulated PEP With PVRV by Intramuscular Route | Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT) | 0.55 International unit per ml |
| PrEP and Simulated PEP With New CPRV by Intramuscular Route | Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT) | 0.64 International unit per ml |
| PrEP and Simulated PEP With New CPRV by Intradermal Route | Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT) | 0.28 International unit per ml |
Primary
Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT)
Blood samples will be drawn on day 374(After the first injection). The samples will be centrifuged and kept as serum under - 20 degree Celsius. The serum will be test by Rapid Florescent Focus Inhibition Test. Rabies neutralizing antibody levels will be determined and expressed in international units per mL. Percentage of Subjects achieving seroconversion (defined as RNab ≥ 0.5 IU/ mL) are determine at each sampling time.
Time frame: on day 374
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| PrEP and Simulated PEP With PVRV by Intramuscular Route | Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT) | 29.16 International unit per ml |
| PrEP and Simulated PEP With New CPRV by Intramuscular Route | Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT) | 45.99 International unit per ml |
| PrEP and Simulated PEP With New CPRV by Intradermal Route | Rabies Neutralizing Antibodies Determine by Rapid Fluorescent Focus Inhibition Test (RFFIT) | 11.93 International unit per ml |
Secondary
Side Effects of the Vaccines. These Include Pain, Swelling, Redness, Myalgia, Rash, Fever. Serious Adverse Events Will Also be Recorded.
There are five injections, on day 0, 7, 28, 360 and 363. The side effects will be record in number and percentage.
Time frame: up to 7 days after each injection