An Open-Label, Single-Treatment, Single-Period, Single Dose, Clinical Phase 1 Study to Assess the Safety and Tolerability of Tetanus Vaccine in Healthy, Adult Subjects in India

Abstract

BACKGROUNDTetanus toxoid vaccine has always been an indelible constituent of the Universal Immunization Programme in India. Besides being given to pregnant women in two doses, it used to be given in children at the ages of ten and sixteen. Gradually with the coming down of the burden of communicable diseases, the vaccine is now even recommended in five years age besides as a prophylactic vaccine for any injury of moderate to severe degree in the tropical situations. With India achieving Neonatal Tetanus Elimination in 2015, the pressures to ensure the availability of cost-effective vaccine has gone up. To cope with the increased demand of this vaccine in India, a bio similar tetanus vaccine vial for the Indian market is proposed and hence the Phase 1 study to validate the dose and the safety of the interventional product was planned at Kalinga Institute of Medical Sciences, Bhubaneswar in the eastern part of India under stringent regulatory guidelines of Central Drug Standards Control Organization (CDSCO), and adhering to the good clinical practice guidelines. MATERIALS AND METHODS24 recruits (healthy adults aged 18-45 years) were taken up for the study with lab screening for blood parameters both preand seven days post vaccination. 23 subjects completed the study as per the protocol and were included in the Efficacy Analysis. Only solicited local adverse events were reported in the trial. Total number of solicited adverse events reported in the trial was 15 (62.5%) The maximal incidence of any local reaction after immunizations within 7 days of vaccination was 58.3% (Pain/Tenderness) followed by swelling/induration in 1 (4.2) subject. RESULTSIgG antibody response after single dose of vaccine was optimal in study population. There is a statistically significant difference between pre-vaccination and post-vaccination values for IgG response against Tetanus antibodies, after single dose. Prevaccination GMT of study changed from 2.24 IU/ml to 12.81 IU/ml, indicating significant results. CONCLUSIONIn our study, in a mixed age and gender group, the seroconversion was nearly 76% and the AEs were 62.5% all of which subsided on their own without medication, which suggests that the vaccine is effective and can proceed onto Phase 2 and 3 trials for further in-depth assessments of the safety and primarily immunogenicity of the vaccine.