Safety and Immunogenicity of ID vs IM Rabies Vaccine
ConditionRabies
Trial statusNot yet recruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age5+
SponsorInternational Centre for Diarrhoeal Disease Research, Bangladesh
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Healthy volunteers aged >4 years
Able to comply with the research process and provide informed consent
Able to attend all the scheduled visits and comply with the trial procedures
Medical history and clinical examination demonstrating that the subject is healthy
Disqualifiers
Subjects participating in other clinical trials in the 4 weeks preceding the first trial vaccination dose
Subjects with a history of previous rabies vaccination (either pre- or post-exposure prophylaxis)
Subjects with a history of receiving Rabies immunoglobulin (Ig (human/equine) prior to the study
Subjects with a fever (≥37.2°C) or any moderate or severe acute illnesses or active infections on the day of vaccination
Trial design
Design model
Parallel
Treatments tested in this trial
Rabies vaccine
Biological/VaccineThe 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.
Rabies vaccine
Biological/VaccineRabies 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.
Treatment groups
90 Participants
are divided into 2 treatment groupsGroup A: Test Arm-1Experimental treatment 1 intervention
Group B: Reference Arm-2Active comparator 1 intervention
Trial outcomes
Primary outcomes
1
Seroconversion Rate
Rabies Virus Neutralizing Antibody: ≥ 0.5 IU/mL
Time frame
14 days, 28 days, and 180 days following the completion of vaccination dosesSecondary outcomes
1
Number of participants with treatment-related serious adverse events as assessed by CTCAE v5.0
Zero serious adverse events reported by the participants by the end of the study will be considered as a safety measure.
Time frame
Participants will be followed up 14 days, 28 days, and 180 days following the completion of vaccination doses. They will also contact the research team for self-reporting of adverse events.2
Number of participants with post-vaccination laboratory abnormalities
Number of participants with clinical laboratory values outside the following reference ranges will be zero: i. Haemoglobin: 13.5 to 17.5 g/dL in adult males, 12 to 16 g/dL in adult females, 12.5 to 16.1 g/dL in male children of 10-17 years, 12 to 15 g/dL in female children of 10-17 years, 11.5 to 14.5 g/dL in children aged 5-9 years. ii. Red blood cell count: 4.3 to 5.7x10\^8/mm3 in adults, 3.5 to 4.7x10\^8/mm3 in children aged 10-17 years, and 3.3 to 4.3x10\^8/mm3 in children aged 5-9 years. iii. Platelet count: 150 to 400 x 103/mm3 iv. Total white blood cell count: 4.5 to 11 x 103/mm3 a. Neutrophils: 57%-67% b. Lymphocytes: 23%-33% c. Monocytes: 3%-7% d. Eosinophils: 1%-3% e. Basophils: 0%-1% v. Serum Electrolytes - 1. Na+: 135-145 mmol/L 2. K+: 3.5-5.3 mmol/L 3. Mg2+: 0.6-1.1 mEq/L 4. Cl-: 98-108 mmol/L vi. Random Blood Sugar: \<200 mg/dL vii. Renal Function test: creatinine: 0.6-1.3 mg/dL viii. Liver Function Test - a. SGPT: 3 to 48 U/L b. Aspartate Aminotransferase (AST): 0 to 55 U/L
Time frame
The number of participants with post-vaccination laboratory values will be assessed on day 21 and day 187 of the study.3
Number of participants with post-vaccination abnormalities in vital signs
There will be no clinically significant deviation from these normal ranges in all participants: i. Oral temperature: 97°F to 99°F. ii. Respiratory rate: 15 to 25 breaths/min in children aged 5 to 9, 15 to 20 breaths/min in children aged 10 to 17, and 12 to 20 in individuals aged 18 years and above. iii. Blood pressure (BP): 120 to 129 systolic BP and 70-90 Diastolic BP. iv. Pulse rate: 60 to 100 beats per min.
Time frame
Vital signs will be evaluated on the day of check-in (day 0), day 7, and during post-vaccination follow-up (day 21, 35, and 187); 30 minutes before dosing on vaccination days4
Number of participants with post-vaccination abnormalities found in physical examination
A complete general and systemic examination will be conducted by a physician including (at a minimum) a thorough examination of the following: General and Systemic examination includes the Head, Neck, Eyes, Ears, Nose, Throat, skin and appendages, Renal, Cardiovascular, Pulmonary, Urology, Reproductive, Endocrine, etc.
Time frame
General and systematic examination will be conducted on check-in (Day 0), day 7, and during post-vaccination follow-up (Days 21, 35, and 187) andSponsors and contacts
Click on the lead sponsor to view all of their trials.
International Centre for Diarrhoeal Disease Research, Bangladesh
Lead sponsor
Popular Pharmaceuticals PLC.
Collaborator
Source ClinicalTrials.gov
This trial is not recruiting at the moment. You can still explore other options: