Immunogenicity and safety of HavisureTM vaccine developed by Human Biologicals Institute in healthy subjects of 12 months to 49 years of age: A phase II/III, randomized, single blind, non-inferiority study.

BACKGROUND: Hepatitis A is an inflammation of the liver caused by the hepatitis A virus (HAV). It is transmitted mainly because of poor personal hygiene via the faecal/oral route through ingestion of contaminated food or water or through the direct contact with an infectious person. Though most of the infected individuals recover from the infection, a few may develop fatal fulminant hepatitis. In this randomized, multicenter study, immunogenicity and safety of Havisure™ vaccine of Human Biologicals Institute was compared with Havrix® vaccine. METHODS: The study was carried out in 528 eligible healthy subjects, in two age groups across eight centres in India. Group A included subjects of 19-49 years and Group B subjects of 12 months to below 19 years of age. All subjects received two doses of either Havisure™ vaccine or Havrix® vaccine as per randomization at six months interval. Blood samples for antibody titre estimation were collected before vaccination and 4-6 weeks after 2nd dose of vaccination. Immunogenicity was assessed by estimating seroconversion rate, seroprotection rate, and geometric mean titres of antibodies. Safety was evaluated by collection and analysis of data on solicited and unsolicited adverse events. RESULTS: Of 528 enrolled subjects, 493 subjects completed the study. There was 100% seroconversion and seroprotection in both the vaccine arms. There was no statistical difference in the geometric mean titres between the two vaccine arms. Pain and swelling at the site of injection were the most common local adverse events whereas fever and headache were the most common systemic adverse events observed in both vaccine arms. No serious adverse event was reported in the study. CONCLUSION: The study results indicate that the Havisure™ vaccine is immunogenic and safe when administered to healthy subjects of 12 months to 49 years of age, and is non-inferior to Havrix® Vaccine.

Safety and immunogenicity of inactivated hepatitis-A vaccine developed by Human Biologicals Institute in two age groups of healthy subjects: A phase I open label study.

BACKGROUND: Hepatitis-A is an acute viral infection of the liver. Hepatitis-A virus has worldwide spread and is endemic in India. Though the disease is self-limiting in most cases, outbreaks are reported frequently from both developing and developed countries of the world. Severity and fatality occur more among infected symptomatic adults. The infection can be prevented with proper and timely immunization. This phase I, single arm, open label, multicenter trial was designed to assess the safety and immunogenicity of the inactivated hepatitis-A vaccine developed by Human Biologicals Institute when administered in a single dose in two age groups of healthy subjects. METHODS: This study was carried out in 55 subjects in two healthy age groups at two centers in India. Group A included subjects of 19-49 years and group B subjects of 12-18 years of age. Enrolled subjects received a single dose of inactivated hepatitis A vaccine. Blood samples were collected at baseline and 4-6 weeks after vaccination. Safety was assessed by collection and analysis of data on solicited and unsolicited adverse events and immunogenicity was assessed by estimating the seroconversion rate, seroprotection rate and the geometric mean titres of antibodies. RESULTS: Among the 55 subjects enrolled, 15 reported adverse events. No serious adverse event was reported. Pain at the injection site was the lone local adverse event. Systemic adverse events reported in Group A were: fatigue, headache, diarrhoea, fever, anorexia, nausea and upper respiratory tract infection, whereas there was no systemic event reported in Group B. There was 100% seroconversion and seroprotection and significant rise in antibody titre levels were observed in both the groups post vaccination. CONCLUSIONS: This study found HBI inactivated hepatitis-A vaccine to be safe and highly immunogenic when administered as a single dose in adolescent and adult subjects.

Immunogenicity and safety of a liquid Pentavalent (DTwP-Hb-Hib) combination vaccine manufactured by Human Biologicals Institute in 6-8 weeks old healthy infants: A phase III, randomized, single blind, non-inferiority study.

BACKGROUND: A liquid Pentavalent (DTwP-Hb-Hib) combination vaccine, developed by Human Biologicals Institute, underwent a Phase III clinical study in India. In this randomized, single blind, non-inferiority study, the immunogenicity and safety of this Investigational vaccine was compared with Pentavac SD® vaccine in 6-8 weeks old healthy infants. METHODS: A total of 405 healthy infants aged 6-8 weeks old were randomized in 2:1 ratio to receive three doses of either the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine or Pentavac SD® vaccine at four to six weeks interval. Immunogenicity was compared by estimation of antibody titers before the first dose and 4-6 weeks after the third dose of vaccination. Safety of each vaccine was assessed and compared by collection of data on solicited and unsolicited adverse events throughout the study period. RESULTS: Out of a total of 405 enrolled subjects, 387 subjects completed the study. The seroconversion rates, seroprotection rates and geometric mean titres of the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine group were found to be comparable and non-inferior to the Pentavac SD® vaccine group at 4-6 weeks after the third dose of vaccination. Pain, erythema and swelling at the site of injection were found to be the most common local adverse events whereas fever, irritability and unusual crying were found to be the most common systemic adverse events in both the vaccine groups. No vaccine related serious adverse event was reported. In this study, both the Investigational vaccine as well as the Comparator vaccine were found to be immunogenic and well tolerated. CONCLUSION: After assessment of the results of the study it was concluded that the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine developed by Human Biologicals Institute was immunogenic and safe when administered to infants aged 6-8 weeks and was non-inferior in immunogenicity and safety to Pentavac SD® vaccine. Clinical Trial Registry of India Identifier: CTRI/2016/01/006541.