Hepatitis B Virus Vaccination in HIV-positive Patients and Individuals at High Risk for HIV Infection

Hepatitis B Virus Vaccination in HIV-positive Patients and Individuals at High Risk for HIV Infection: an Open-label Randomized Clinical Trial

The primary aim of this open-label, randomized control trial is to compare the immunogenicity at week 28 after 20µg HBV vaccine (at week 0, 4, 24) versus 40µg HBV vaccine (40-µg at week 0, 4, 24 week) among HIV-positive patients or HIV-negative MSM who were born in Taiwan after July 1986 and tested negative for all HBV serological markers. The secondary aims are to assess the safety of double-dose HBV vaccination, the proportions of high-level responders (anti-HBs antibody >100 mIU/ml) at weeks 28 and 48, the serological responses at week 48, and incident HBV infection (indicated by appearance of anti-HBc and/or HBsAg) at week 48.

Study Overview

• Status: Recruiting
• Conditions: HIV Infections; Immunization; Infection; Viral Hepatitis B
• Intervention / Treatment: Drug: Engerix-B

Detailed Description

I. Study procedures:

1. Well explain, complete inform and consent documents
2. A blood test for hepatitis B surface antigen (HBsAg), anti-hepatitis B surface antibody (anti-HBs antibody), anti-hepatitis B core antibody (anti-HBc antibody), anti-HCV and RPR will be performed first.
3. The patients with all negative seromarkers (within 1 month) will be allocated to two groups (random blank=4), a standard-dose booster of 20µg and a double-dose booster of 40µg. For patients receiving 40µg, two 20µg of vaccines are injected at both sides of deltoid muscles. The schedules of booster vaccination are the same in two groups, which is at 0, 1, 6 months.
4. To detect and manage possible immediate and severe allergic reaction, patients who received vaccination will be observed for 30 minutes after injection.
5. The solicited adverse effect will be recorded on the diary card if occurred in 7 days after each dose of vaccination.
6. The titer of hepatitis B surface antibody will be examined before booster vaccination, at the 4th week, the 24th week, 28th week, 48th week. By comparing the responses in the two groups, the effect of different doses of booster vaccination can be evaluated. For those HIV-negative individuals at baseline, HIV screening test will be evaluated every 6 months during the study, at the 24th week, the 48th.
7. To screen the acquisition of hepatitis B, the anti-HBc antibody and HBsAg will be examined at the 48th week
8. To screen the acquisition of hepatitis C and syphilis, anti-HCV and RPR will be examined at the 24th week, the 48th week
9. The results of the study will be informed by phone or the physician during the follow-up care.
10. The serum/blood samples will be preserved in the research lab of the department of internal medicine and kept for 20 years. During this period, the sample will be applied or used in other studies after the patients and the Research Ethics Committee both agreed.
11. During the follow-up care, the treatment or record of hospitalization will be recorded or reviewed.
12. The participants will drop out of clinical trial when protocol violation occurred or the participant is not willing to continue.

• Study Type: Interventional
• Enrollment (Anticipated): 575
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Chien-Ching Hung, MD, PhD; Phone Number: 67552 +886-2-23123456; Email: hcc0401@ntu.edu.tw
• Study Contact Backup: Name: Hsin-Yun Sun, MD; Phone Number: +886-2-23707772; Email: hysun@ntu.edu.tw

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Chien-Ching Hung, MD, PhD; Phone Number: 67552 +886-2-23123456; Email: hcc0401@ntu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Men who have sex with men (MSM)
• Birth date after 1986/7/1 and aged 20 years or older
• Seronegative for HBsAg, anti-HBs (<10 mIU/ml), and anti-HBc at screening (within 1 month of the first dose)
• Regularly receiving HIV care for HIV-positive patients over the past 6 months
• Seeking VCT for at least once for HIV-negative patients over the past 12 months

Exclusion Criteria:

• Active infection or malignancy within 12 months of screening
• Receiving chemotherapy, immunosuppressant, or IVIG within 12 months of screening
• Received higher than 5 mg of prednisolone, including IV, oral, or topical form, per day for more than 1 weeks within 6 months of screening
• Receiving HBV vaccination within 1 months of screening, or being allergic to HBV vaccine
• Receiving other vaccination within 1 months of screening, such as influenza, pneumococcus, HPV, HAV, varicella vaccine.
• Stage 4 and 5 of chronic kidney disease (GFR<30 mL/min/1.73m), or receiving dialysis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Standard dose (20µg); Three doses of 20µg HBV vaccine given intramuscularly at week 0, 4, 24.	Drug: Engerix-B; The vaccine contains HBsAg which was produced by genetic engineering yeast. It stimulates the active immunity generated by human immune system toward the HBsAg.
EXPERIMENTAL: Double dose (40µg); Three doses of 40µg HBV vaccine given intramuscularly at week 0, 4, 24.	Drug: Engerix-B; The vaccine contains HBsAg which was produced by genetic engineering yeast. It stimulates the active immunity generated by human immune system toward the HBsAg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaccine efficacy	The proportion of patients with Anti-HBs antibody higher than 10mIU/ml	week 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High-titer response	The proportion of patients with Anti-HBs antibody higher than 100mIU/ml	week 28
Long-term efficacy	The proportion of anti-HBs antibody titers higher than 10mIU/ml	48 weeks
Long-term high-titer response	The proportion of anti-HBs antibody titers higher than 100mIU/ml	48 weeks
Hepatitis B incident infection rate	new HBsAg and anti-HBc antibody seroconversion	48 weeks,
Hepatitis C infection and syphilis infection rate	new hepatitis C infection and syphilis infection	at 24 week, 48 weeks
HIV seroconversion among HIV-negative MSM	new HIV seroconversion among HIV-negative MSM	at 24 weeks, 48 weeks

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: Taipei Veterans General Hospital, Taiwan
• Investigators: Principal Investigator: Chien-Ching Hung, MD, PhD, Department of Internal Medicine, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 6, 2017
• Primary Completion (ANTICIPATED): June 1, 2023
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: September 7, 2017
• First Submitted That Met QC Criteria: February 24, 2019
• First Posted (ACTUAL): February 26, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 22, 2020
• Last Update Submitted That Met QC Criteria: May 22, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Slow Virus Diseases; HIV Infections; Infections; Communicable Diseases; Hepatitis B; Hepatitis; Hepatitis A; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: 201608051MIPC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No