Safety and Immunogenicity of ID vs IM Rabies Vaccine

Summary

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.

Conditions

• Rabies

Interventions

BIOLOGICAL

Rabies vaccine

The intradermal rabies vaccine is designed to elicit an immune response in the skin. The skin is composed of three layers, from outermost to innermost: the epidermis, dermis, and hypodermis, where the dermis is further divided into two sub-layers: the superficial papillary dermis and the deeper reticular dermis. The papillary dermis is 100-300 μm thick and is the target layer for ID immunization. This layer is rich in antigenpresenting cells (APCs), including dermal dendritic cells (DDCs) and Langerhans cells. DDCs capture antigens in the dermis and migrate to the regional lymph nodes, which present antigens to T-cells, triggering their activation. Soluble antigens also migrate to lymph nodes, leading to the activation of B-cells. Because of the high concentration of APCs in the dermis, ID delivery of reduced antigen doses (typically 20% to 30% of the standard amount) can elicit immune responses comparable to those achieved with standard doses administered intramuscularly.

BIOLOGICAL

Rabies vaccine

Rabies vaccine is an active immunizing agent used to prevent infection caused by the rabies virus. The vaccine works by causing the body to produce its own protection (antibodies) against the rabies virus.

Sponsors & Collaborators

• Popular Pharmaceuticals PLC.

  collaborator UNKNOWN

• International Centre for Diarrhoeal Disease Research, Bangladesh

  lead OTHER

Principal Investigators

• Shomik Maruf, MSc · International Center for Diarrhoeal Disease Research, Bangladesh

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

5 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-12-15

Primary Completion

2027-05-15

Completion

2027-07-15

Countries

• Bangladesh

Study Locations