Immunogenicity of Rabies Vaccine for Pre Exposure Prophylaxis

Study Overview
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Brief Summary
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The purpose of this study is to compare the effectiveness of a two dose versus a three dose schedule and intramuscular versus intradermal injection for pre-exposure prophylaxis.

Detailed Description
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This is an exploratory vaccine trial to evaluate immunogenicity of a non-licensed dosing schedule and route of administration for a currently FDA licensed rabies vaccine for pre-exposure prophylaxis against rabies infection. The goal of this study is to characterize the immune response and persistence of immunity to a shortened dose schedule and intradermal (ID) administration, relative to the current licensed dosing schedule of the rabies vaccine (3 dose (0, 7, 21 days) IM). Rabies virus is endemic throughout the world due to high rates of both wild and domestic animal rabies and the risk to deployed military in endemic areas is considerable. Currently the commonly supported pre-exposure prophylaxis regimen for rabies, in the United States is comprised of three, 1.0 ml intramuscular (IM) injections of the human diploid cell vaccine (HDCV) or purified chick embryo cell (PCEC) rabies vaccine on days 0, 7, and 21 or 28. Modified, two and three dose schedules of intradermal (ID) injections of 0.1 ml of HDCV and PCEC are utilized outside the US. These two and three dose intradermal schedules share a similar safety and immunogenicity profile to intramuscular vaccinations and are easily boosted at one year after vaccination. A death, from rabies, of a US Soldier returned from Afghanistan underscores the importance of rabies pre-exposure prophylaxis for soldiers and the need to evaluate the safest, most effective means of vaccinating large deploying forces. While the current three dose, 1 ml IM rabies series is effective, a shortened, equally effective vaccination series with significantly smaller dose per injection would greatly improve the logistics and cost associated with universal or even targeted coverage of deploying soldiers. Evaluation of a shorter, smaller-dose, pre-exposure vaccination series for rabies is the goal of this study.

Official Title
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Immunogenicity of a Two vs Three Dose, Intradermal (ID) vs Intramuscular (IM) Administration of a Licensed Rabies Vaccine for Pre-Exposure Vaccination

Conditions
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Rabies

Intervention / Treatment
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* Drug: Rabies vaccine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and non-pregnant females aged ≥ 18 to ≤ 60 years on the day of inclusion Able to comprehend and give informed consent Able to attend all scheduled visits and to comply with all trial procedures Subject in good health, based on medical history and physical examination Exclusion Criteria: Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be post- menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination). Participation in the 4 weeks preceding the first trial vaccination, or planned participation during the present trial period, in another clinical trial investigating a vaccine, drug, medical device, or medical procedure. Previous history of receiving the rabies vaccine. Previous history of receiving rabies immune globulin. Any major psychiatric disorder, such as severe depression, severe anxiety disorder, psychosis, schizophrenia, other major psychiatric disorders, or seizures. History of mild depression or anxiety disorder that is well controlled is not an exclusion criteria. Any history of cardiac arrhythmias, such as: Bradycardia, tachycardia, heart block, SVT, PAC, VF, VT, or any other conduction abnormalities. Use of any immunosuppressive drug , including topical steroids of potency groups I, II or III within 30 days of the study period. Any immunosuppressive disorder, such as HIV, common variable, active cancers or chemotherapy. History of renal insufficiency or requiring dialysis. Any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol. Identified as an employee of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members (i.e., immediate, husband, wife and their children, adopted or natural) of the employee or the Investigator.

Ages Eligible for Study
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Minimum Age: 18 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rabies vaccine IM 3 dose<br>Intramuscular injection: 1mL at 0, 7 and 21 days. An additional 1 mL intramuscular dose at day 365 | Drug: Rabies vaccine<br>* Compare dose schedule and route of administration<br>* Other names: Rabavert;|
| Experimental: Rabies vaccine ID 3 dose<br>Intradermal injection: 0.1mL at 0, 7 and 21 days. A single intramuscular 1 mL dose at day 365 | Drug: Rabies vaccine<br>* Compare dose schedule and route of administration<br>* Other names: Rabavert;|
| Experimental: Rabies vaccine IM 2 dose<br>Intramuscular injection: 1mL at 0, 7 days. An additional 1 mL intramuscular dose at day 365 | Drug: Rabies vaccine<br>* Compare dose schedule and route of administration<br>* Other names: Rabavert;|
| Experimental: Rabies vaccine ID 2 dose<br>Intradermal injection: 0.1mL at 0, 7 days. A single intramuscular 1 mL dose at day 365 | Drug: Rabies vaccine<br>* Compare dose schedule and route of administration<br>* Other names: Rabavert;|
| Placebo Comparator: Placebo IM 1 dose<br>Albumin and saline comparator, Intramuscular injection: 1mL | Drug: Placebo<br>* Placebo<br>* Other names: Albumin;|
| Placebo Comparator: Placebo ID 1 dose<br>Albumin and saline comparator, Intradermal injection: 0.1mL | Drug: Placebo<br>* Placebo<br>* Other names: Albumin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Protective Humoral Immune Response at 1 Month Post First Vaccination. | Percentage of subjects achieving the protective titer of ≥ 0.5 IU/ml against rabies virus | 1 month post first vaccination | 
| Protective Humoral Immune Response 12 Months Post First Vaccination. | Percentage of subjects achieving the protective titer of ≥ 0.5 IU/ml against rabies virus 12 months post vaccinations (prior to boost). | 12 months post first vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Protective Humoral Immune Response 7 Days Post Booster at 12 Months Post First Vaccination. | Percentage of subjects achieving the protective titer of ≥ 0.5 IU/ml against rabies virus at 7 days post boost. | up to 13 months post first vaccination |