Safety and Immunogenicity of ID vs IM Rabies Vaccine

Background:

Burden: Rabies is a viral zoonotic disease that is 100% fatal if left untreated. Globally, Bangladesh is ranked third in terms of rabies infections. In 2009, the estimated human fatality from rabies in Bangladesh surpassed 2,000. However, the death toll has steadily declined to 26 in 2020, owing to the implementation of the 'National Rabies Elimination Program' beginning in 2010, which included the introduction of the cell culture vaccine. Though this infection is entirely preventable by vaccination, the available intramuscular regimen is costly and requires multiple high doses.

Knowledge gap: The safety and immunogenicity of an intradermal rabies vaccine regimen in the Bangladeshi population needs to be assessed to comply with the recommendation of DGDA to obtain approval to be administered through an alternate route.

Relevance: Intradermal rabies vaccine administration is a safe method that reduces the amount of vaccine needed and the number of doses required by producing immunogenicity similar to that of the intramuscular regimen. This translates to 60-80% cost reductions while preserving the safety and immunogenicity of the vaccine. The intramuscular rabies vaccine by Popular Pharmaceuticals PLC has already been granted marketing authorization by DGDA. However, the vaccine's administration via the intradermal route is yet to receive approval from DGDA for marketing as per the regulatory requirements.

Hypothesis: The immunogenicity and safety of the Intradermal rabies vaccine (Popular Pharmaceutical PLC) will be non-inferior to the intramuscular regimen of the same vaccine.

Objectives:

1. To compare the seroconversion level of the intradermal rabies vaccine to the intramuscular regimen by Popular Pharmaceuticals PLC. in healthy Bangladeshi individuals 2. To compare the safety of the intradermal rabies vaccine to the intramuscular regimen by Popular Pharmaceuticals PLC. in healthy Bangladeshi individuals

Methods: This will be an open-label, non-inferiority, single-blinded, randomized controlled trial where the safety and immunogenicity of the intradermal rabies vaccine will be assessed compared with the standard intramuscular regimen, both by Popular Pharmaceuticals PLC., amongst healthy individuals. The study will be conducted at the Infectious Disease and Tropical Medicine Department (Surya Kanta Hospital), Mymensingh Medical College Hospital, Mymensingh. We will enroll 90 participants and randomly assign them to two equal groups: a test group and a reference group. The test groups will receive 0.2 ml Inj. Rabivax intradermally (0.1 ml in each arm), whereas the reference group will receive 1 ml Injectable Rabivax (2.5 IU/ml) intramuscularly. The participants will be followed up on days 21, 35, and 187 for clinical and biochemical evaluation. A comparative analysis of safety and immunogenicity will be conducted on intradermal and intramuscular administration based on the collected data.

Outcome measures/variables:

* A seroconversion level of 0.5 IU/ml or more when tested for Rabies Virus Neutralizing Antibody (RVNA) following intradermal vaccination by Popular Pharmaceuticals PLC. during the study period * Non-inferior safety parameters of the intradermal rabies vaccine regimen in comparison with the available intramuscular regimen by Popular Pharmaceuticals PLC.