Immunogenicity Assessment of Subjects Receiving Rabies Post-exposure Prophylaxis in Cambodia

Study Overview
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Brief Summary
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A rabies virus neutralizing antibody (RVNA) concentration ≥ 0.5 IU/ml at 14 days after immunization is considered a proxy for protection in vaccine efficacy studies. Abridged and dose-sparing vaccination regimens increase accessibility and reduce both direct and indirect costs, especially in resource-constrained countries where RABV prevalence is highest. Several efficacy studies evaluated safety and immunogenicity of abridged regimens in healthy adult volunteers using either four-site intradermal (ID) or intramuscular (IM) regimens, showing them to be safe and immunogenic. Researchers at the Institut Pasteur du Cambodge (IPC) have previously conducted a retrospective study on clinical outcome at ≥6 months in 3318 Cambodians who received intradermal Vero cell vaccine post-exposure prophylaxis after a bite by a rabid or sick-looking but untested dog in 2003-2014. Here, the investigators could show that there was no significant difference in survival among patients who received 3 versus 4 sessions of the Thai Red Cross (TRC) ID regimen. In a separate study, investigators measured antibody responses in order to evaluate the immunogenicity of the TRC regiment after 3 sessions versus 4 sessions. The investigators did not observe an increase in rabies virus seroneutralization titers 14 days after the fourth immunization compared to 14 days after the third immunization. These results contributed to changes endorsed by the WHO in its April 2018 guidelines. The Institut Pasteur du Cambodge (IPC) regimen of three PEP sessions of two-site ID 0.1 mL vaccine doses each at days 0, 3 and 7 is the first one-week PEP regimen to be recommended. In the current research project, the aim is to compare further different PEP vaccination strategies in a real life setting of individuals attending the rabies vaccination center at Institut Pasteur du Cambodge (IPC) in Phom Penh, Cambodia. The antibody kinetics and cellular immune responses in patients following either the one-week, 2-site ID regimen (IPC regimen) or the two-week IM regimen (4-dose regimen) as well as the participants' survival for both protocols after 6 months are evaluated.

Official Title
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Immunogenicity Assessment of Subjects Receiving Rabies Post-exposure Prophylaxis in Cambodia

Conditions
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Rabies Post-exposure Prophylaxis

Intervention / Treatment
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* Biological: Intramuscular (IM) rabies post-exposure prophylaxis
* Biological: Intradermal (ID) rabies post-exposure prophylaxis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects entering a rabies post-exposure vaccination course whatever the vaccine used with or without administration of rabies immunoglobulin (RIGs). Subjects with ability to attend all scheduled visits and to comply with all study procedures Exclusion Criteria: Subjects with history of previous rabies vaccination
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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| IM, <15 years old<br>Group with Intramuscular (IM) rabies post-exposure prophylaxis | Biological: Intramuscular (IM) rabies post-exposure prophylaxis<br>* one-site, 0.5 mL at Day 0, D3, D7 and D14<br>|
| IM, 15 years old and older<br>Group with Intramuscular (IM) rabies post-exposure prophylaxis | Biological: Intramuscular (IM) rabies post-exposure prophylaxis<br>* one-site, 0.5 mL at Day 0, D3, D7 and D14<br>|
| ID, <15 years old<br>Group with Intradermal (ID) rabies post-exposure prophylaxis | Biological: Intradermal (ID) rabies post-exposure prophylaxis<br>* two-site, 0.1 mL at Day 0, D3 and D7<br>|
| ID, 15 years old and older<br>Group with Intradermal (ID) rabies post-exposure prophylaxis | Biological: Intradermal (ID) rabies post-exposure prophylaxis<br>* two-site, 0.1 mL at Day 0, D3 and D7<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of the level of rabies virus neutralizing antibodies at 14 days and 18 days after first dose among patients receiving post-exposure prophylaxis (PEP) using intramuscular (IM) and intradermal (ID) protocols | Assessment of humoral immune response (rabies virus neutralizing antibodies - RVNA - titers measured with Fluorescent Antibody Virus Neutralization test - FAVN - by local laboratory) at different time points: at baseline before the first PEP dose, 14 days and 28 days after the first PEP dose, in each study group (IM / ID) | Day 0 (the first PEP dose), then 14 days and 28 days after Day 0 in each study group (IM / ID) |