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

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.

Study Overview

• Status: Completed
• Conditions: Rabies Post-exposure Prophylaxis
• Intervention / Treatment: Biological: Intramuscular (IM) rabies post-exposure prophylaxis; Biological: Intradermal (ID) rabies post-exposure prophylaxis

• Study Type: Observational
• Enrollment (Actual): 215

Contacts and Locations

Study Locations

• Cambodia
  • Phnom Penh, Cambodia
    • Institut Pasteur du Cambodge (IPC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients seeking for rabies post-exposure prophylaxis (PEP) at the rabies prevention center of Institut Pasteur du Cambodge

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Institut Pasteur du Cambodge
• Collaborators: Sanofi Pasteur, a Sanofi Company
• Investigators: Principal Investigator: Sowath LY, PhD, Institut Pasteur du Cambodge (IPC)

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2020
• Primary Completion (Actual): April 1, 2022
• Study Completion (Actual): April 30, 2022

Study Registration Dates

• First Submitted: October 16, 2022
• First Submitted That Met QC Criteria: January 11, 2023
• First Posted (Estimate): January 13, 2023

Study Record Updates

• Last Update Posted (Estimate): January 13, 2023
• Last Update Submitted That Met QC Criteria: January 11, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Mononegavirales Infections; Rhabdoviridae Infections; Rabies
• Other Study ID Numbers: RAB00056

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No