Non Inferiority Trial of Locally Manufactured 'Hepa-B' Vaccine in Bangladesh.

February 10, 2022 updated by: International Centre for Diarrhoeal Disease Research, Bangladesh

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.

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%.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

158

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bangladesh
    • Mirpur
      • Dhaka, Mirpur, Bangladesh, 1216
        • Mirpur Field Office

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 43 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Considered healthy as per medical judgment of the investigator
  2. Age: 20 to 45 years
  3. Sex: Male, Female and Transgender
  4. For married women, a negative urine pregnancy test (Rapid Diagnostic Test) during screening and prior to first, second and third dose of vaccination.Moreover, medical history will be taken thoroughly by study physician from the woman of childbearing age to completely exclude the probability of pregnancy.The women who are married and living with a partner must agree to use a reliable contraceptive method to prevent pregnancy until final follow-up following vaccination. However abstinence is also acceptable.

Exclusion Criteria:

  1. Prior history of hepatitis B infection
  2. Vaccination with any hepatitis B vaccine
  3. Recent febrile illness (within 2 weeks)
  4. Known or suspected hypersensitivity to any component of Hepatitis B vaccine (e.g., aluminium, yeast).
  5. History of received hepatitis B immune globulin (HBIG), serum immune globulin, or any other blood-derived product.
  6. Known or suspected impairment of immunologic function or recent use of immunomodulatory medications (e.g., systemic corticosteroids) more than 14 days with in last 6 months. Does not include topical and inhaled steroids.
  7. Receipt of investigational drugs or other investigational vaccines within 3 months prior to first injection with the study vaccine.
  8. Pregnant women, nursing mothers, and women planning to become pregnant within the study period.
  9. HBsAg reactive, anti-HBs antibody (≥10mlU/ml), anti-HBc (total) reactive, and abnormal liver function test [serum alanine aminotransferase (ALT) level], serum creatinine and CBC (As mentioned in Appendix IV).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Hepa B
79 participant will be randomly assigned to the test group for receiving the locally produced 'Hepa-B' vaccine.
Biological: Hepa-B
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.
Active Comparator: Engerix B
79 participant will be randomly assigned to the comparator group for receiving 'Engerix-B' vaccine.
Biological: Engerix B
.'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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
1. The test vaccine will induce similar seroprotection rates at 7 months compared to comparator vaccine.
Time Frame: At 7 months(Study day 210)
The test vaccine will induce similar seroprotection rates to hepatitis B at 7 months ( study day 210) comparator vaccine.
At 7 months(Study day 210)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Ratio of the GMTs of test and comparator vaccines in different time points.
Time Frame: 30 days after last vaccination
Comparison of the geometric mean titre among the test and the comparator group.
30 days after last vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

International Centre for Diarrhoeal Disease Research, Bangladesh

Investigators

  • Study Chair: Firdausi Qadri, PhD, International Centre for Diarrhoeal Disease Research, Bangladesh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 29, 2018

Primary Completion (Actual)

May 27, 2019

Study Completion (Actual)

June 3, 2019

Study Registration Dates

First Submitted

May 30, 2018

First Submitted That Met QC Criteria

August 8, 2018

First Posted (Actual)

August 13, 2018

Study Record Updates

Last Update Posted (Actual)

February 11, 2022

Last Update Submitted That Met QC Criteria

February 10, 2022

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PR-18020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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