Clinical trial NCT03854630: Hepatitis B Virus Vaccination in HIV-positive Patients and Individuals at High Risk for HIV Infection
Official title: Hepatitis B Virus Vaccination in HIV-positive Patients and Individuals at High Risk for HIV Infection: an Open-label Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Viral Hepatitis B
Immunization; Infection
HIV Infections
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
Collaborators: name: Taipei Veterans General Hospital, Taiwan
First posted: 2019-02-26
Enrollment: 575
Sex: MALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Vaccine efficacy
timeFrame: week 28
Secondary outcomes:
measure: High-titer response
timeFrame: week 28
measure: Long-term efficacy
timeFrame: 48 weeks
measure: Long-term high-titer response
timeFrame: 48 weeks
measure: Hepatitis B incident infection rate
timeFrame: 48 weeks,
measure: Hepatitis C infection and syphilis infection rate
timeFrame: at 24 week, 48 weeks
measure: HIV seroconversion among HIV-negative MSM
timeFrame: at 24 weeks, 48 weeks
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Department of Internal Medicine, National Taiwan University Hospital
name: Chien-Ching Hung, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: