Immune Response in Adults to PrEP and Simulated Booster PEP With a New CPRV

Study Overview
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Brief Summary
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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
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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.

Official Title
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Immune Response in Adults to Pre-exposure Rabies Vaccination and Simulated Post-exposure Rabies Booster Vaccination With a New Chromatographically Purified Vero-cell Rabies Vaccine(SPEEDA®) : a Randomized Controlled Trial With Purified Vero-cell Rabies Vaccine (PVRV)

Conditions
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Efficacy of the New CPRV

Intervention / Treatment
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* Biological: New Chromatographically Purified Vero-cell Rabies vaccine(new CPRV).


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PrEP and Simulated PEP with PVRV by intramuscular route<br> | Biological: New Chromatographically Purified Vero-cell Rabies vaccine(new CPRV).<br>* new CPRV 0.1 ml intradermal route and 0.5 ml intramuscular route are the experimental intervention<br>|
| Experimental: PrEP and Simulated PEP with new CPRV by intramuscular route<br> | Biological: New Chromatographically Purified Vero-cell Rabies vaccine(new CPRV).<br>* new CPRV 0.1 ml intradermal route and 0.5 ml intramuscular route are the experimental intervention<br>|
| Experimental: PrEP and Simulated PEP with new CPRV by intradermal route<br> | Biological: New Chromatographically Purified Vero-cell Rabies vaccine(new CPRV).<br>* new CPRV 0.1 ml intradermal route and 0.5 ml intramuscular route are the experimental intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | on day 0 | 
| 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. | on day 28 | 
| 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. | on day 42 | 
| 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. | on day 360 | 
| 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. | on day 374 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | up to 7 days after each injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CPRV, SPEEDA, intradermal, pre-exposure, booster