Non Inferiority Trial of Locally Manufactured 'Hepa-B' Vaccine in Bangladesh.
Condition: Hepatitis B Infection
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Hepatitis B is a common and serious infectious disease of the liver, affecting millions of
      people throughout the world. Persistent Hepatitis B virus infections may cause development of
      chronic hepatic insufficiency, cirrhosis and hepatocellular carcinoma. Adding to that,
      Hepatitis B Virus carriers can transmit the disease for many years. It is transmitted through
      blood or other body fluids infected with the Hepatitis B virus. It is a major cause of
      morbidity and mortality in countries like Bangladesh. Immunization with Hepatitis B vaccine
      has been proved effective to prevent HBV infection. But the vaccines, which are recommended
      till now, are expensive. Locally manufactured Hepatitis B vaccine will be safe, cost
      effective and affordable for all.

      The test vaccine will induce similar seroprotection rates to hepatitis B one month
      post-vaccination and at 7 months, one month after the third dose of vaccine compared to
      reference vaccine. This will be done by comparing the percentages of participants with ≥10
      mIU/ml anti-HBs by vaccinated with either Hepa B or Engerix B vaccine. The non-inferiority
      margin will be 10%.
    

Detailed description: 
      Research Protocol Title: A randomized observer-blinded non inferiority trial to evaluate the
      immunogenicity and safety of locally manufactured Hepatitis B Vaccine 'Hepa B' in Bangladeshi
      healthy adults.

      Background (brief):

        1. Burden: Hepatitis B is a serious and common infectious disease of the liver, affecting
           millions of people throughout the world1. The severe pathological consequences of
           persistent Hepatitis B virus (HBV) infections include the development of chronic hepatic
           insufficiency, cirrhosis and hepatocellular carcinoma (HCC) 1. More than 2000 million
           people alive today have been infected with HBV at some time in their lives. 1 Of these,
           about 350 million remain infected chronically and become carriers of the virus. 1 Three
           quarters of the world's population live in areas where there are high levels of
           infection 1. Every year there are over 4 million acute clinical cases of HBV and about
           25% of carriers, 1 million people a year, die from chronic active hepatitis, cirrhosis
           or primary liver cancer 1. HBV prevalence in Bangladesh is 2.3 to 9.7 percent with an
           approximate carrier pool of 10 million. These include healthy adult population 4.4 to
           9.7%, healthy children 3%, school girls 2.3%, a rural community 6.4%, and slum
           communities 3.8%.2,3 About 25-30% population of Bangladesh do not test positive for
           HBsAg rather test positive for another marker of HBV that is with anti HBc4. Thus about
           50 million Bangladeshi people are infected with HBV and transmission of their blood and
           body fluids may transmit HBV to healthy uninfected person4.

        2. Knowledge gap: The prevention of chronic HBV infection has become a high priority in the
           global community. Immunization with hepatitis B vaccine is the most effective means of
           preventing HBV infection and its consequence. Vaccine against hepatitis B was introduced
           in the early 1980s. Recombinant vaccines became available in the mid 1980s.1 Bangladesh
           introduced Hepatitis B vaccine in the EPI, immunization schedule in a small scale from
           2003 but nationwide it was available from 20095 .The HBV prevalence in Bangladesh is 2.3
           to 9.7 percent with an approximate carrier pool of 10 million. These include healthy
           adult population 4.4 to 9.7%, healthy children 3%, school girls 2.3%, a rural community
           6.4%, and slum communities 3.8%2,3 . WHO recommended to vaccinate all children and
           adolescents younger than 18 years-old living in low or intermediate endemicity and also
           in these settings to vaccinate people in high-risk groups who may acquire the
           infection6. Currently there is no locally manufactured Hepatitis B vaccine available in
           Bangladesh. The results of this study will provide information regarding the
           immunogenicity and safety of the locally manufactured Hepatitis B vaccine 'Hepa B' as a
           test vaccine using 'Engerix B' as a comparator vaccine in a non inferiority study
           design.

        3. Relevance: The study of this locally manufactured Hepatitis B vaccine, 'Hepa B' among
           adults will be able to give us information regarding the safety and immunogenicity of
           the vaccine and compare this locally produced Hepatitis B vaccine 'Hepa B' with 'Engerix
           B' vaccine. Hepa B has undergone technology transfer from BioBridge company in Pune,
           India. Incepta and BioBridge entered into an agreement for transfer of technology for
           manufacture of locally produced 'Hepa- B' in Bangladesh. The regulatory requirements as
           well as licensure of the vaccine will be initiated in Bangladesh. Currently there are no
           locally manufactured Bulk of Hepatitis B available in Bangladesh. Once these clinical
           trials will be completed, Incepta will apply for licensure of Hepa B to the Bangladesh
           DGDA. This will significantly reduce the cost of vaccine and ensure availability to the
           people of Bangladesh. Currently the imported vaccine "Engerix B 1 ml" is sold at a price
           of 608 taka where as Incepta can sell the product at 500 taka. So, in each unit price
           difference is 108 taka. As each individual needs 3 doses, so it will be 324 taka saved
           for each subject. Thus the vaccine cost could be significantly reduced and save a large
           amount of foreign currency of Bangladesh Government.

           Hypothesis (if any): Locally produced intramuscular non-infectious recombinant DNA
           vaccine Hepa-B is non inferior in terms of immunogenicity and safety among adults in
           Bangladesh as compared to Engerix-B.

           Objectives:

           Primary Objective

           • To evaluate and compare the immunogenicity and safety of locally produced Hepatitis B
           vaccine 'Hepa-B' with Engerix-B among healthy adults in Bangladesh.

           Methods:

           This will be a randomized observer-blinded and comparative study on a total of 158
           healthy adult participants. Hepa B (Test group) and Engerix B (Comparator Group)
           controlled non inferiority study in healthy adult (20-45 years of age). 79 participants
           will receive Hepa B 1.0 ml and another 79 participants will receive Engerix B 1.0 ml
           Outcome measures/variables: To evaluate and compare the immunogenicity and safety of
           locally produced Hepa B with Engerix B.

           Primary Objective:

           • To evaluate and compare the immunogenicity and safety of locally produced Hepatitis B
           vaccine 'Hepa B' with 'Engerix B' in healthy adults in Bangladesh.

           Primary end points:

             1. The test vaccine will induce similar seroprotection rates to hepatitis B one month
                post vaccination and at 7 months, one month after the third dose of vaccine
                compared to comparator vaccine. This will be done by comparing the percentage of
                participants with ≥10 mIU/ml anti HBs after vaccination with either Hepa B or
                Engerix B vaccine. The non inferiority margin will be 10%.

             2. Number of immediate reactions reported within 30 minutes after vaccination

             3. Number of solicited adverse events (prelisted in the participant's memory aid)
                occurring up to 4 days following vaccination.

             4. Number of unsolicited AEs up to 30 days after each dose of vaccination.

             5. Occurrence of serious adverse events (SAEs) throughout the trial.

           Secondary end points:

           1. The Ratio of the GMTs of test and comparator vaccines in different time points.
    

Intervention name(s): Hepa-B; Engerix B
Intervention type(s): Biological; Biological
Intervention description(s): Incepta will manufacture a locally produced Hepatitis B vaccine named 'Hepa- B' which contain recombinant Hepatitis B surface antigen obtaine. This bulk is formulated to prepare finished dosage to manufacture large scale in fully GMP compliant plant. Incepta has conducted preclinical study at Bioneed, India. After successful completion of preclinical study, this non inferiority clinical trial with innovator product is needed for Licensure in Bangladesh.; .'Engerix B' is a recombinant DNA hepatitis B vaccine. It is sterile suspension of purified surface antigen of hepatitis B virus obtained by culturing genetically yeast cells (Saccharomyces cerevisiae cells), which carry the gene that codes for HBsAg
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Eligible participants will be assigned to receive the Hepa-B Vaccine and Engerix-B Vaccine, in a 1:1 ratio across the target population according to the randomization schedule. The study agents (Hepa B Vaccine or Engerix B Vaccine) will be labelled as per the randomization list.79 participant will receive locally produced Hepa-B Vaccine and 79 participant of comparator group will receive Engerix B Vaccine.
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Hepatitis B, Seroconversion, Seroprotection, Vaccine