Immunogenicity of Hepatitis B Vaccination in HIV-infected Adults

• Sponsor: Suping Wang (Other)
• Overall Status: Completed
• CT.gov ID: NCT03316807
• Collaborator: Centers for Disease Control and Prevention, China (Other)
• Enrollment: 182
• Arms: 2
• Actual Duration (Months): 45

Study Details

Study Description

Brief Summary

Uptake, adherence, and completion of vaccination among HIV-infected adults were low, and their immune function and immune response to hepatitis B vaccination were also suboptimal, indicating that the current practice of hepatitis B vaccination can't protect HIV-infected adults from HBV infection. And the persistence of immunity induced by hepatitis B vaccination remains a challenge.

This is a randomized, open-label trial, conducted among HIV-infected adults with drug rehabilitation. This study will compare the immunogenicity, immune persistence, and safety of three intramuscular 20µg and 60µg recombinant hepatitis B vaccines at months 0, 1, and 6 among HIV-infected adults.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B Vaccine	Biological: 60 µg dose hepatitis B vaccine; Biological: 20 µg dose hepatitis B vaccine	Phase 4

Detailed Description

Participants are randomized in a ratio of 1:1 into 20 µg recombinant hepatitis B vaccine group or 60µg recombinant hepatitis B vaccine group. The 20 µg group will receive three intramuscular injections of the 20 µg recombinant hepatitis B vaccine, while the 60 µg group will receive three intramuscular injections of the 60 µg dose at months 0, 1 and 6, respectively. HBsAg and anti-HBs will be tested during the study period. Adverse reactions will be recorded after vaccination.

Study Design

• Study Type: Interventional
• Actual Enrollment: 182 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Persistence of Intramuscular High Dose Recombinant Hepatitis B Vaccine in HIV-infected Adults in China
• Actual Study Start Date: Oct 1, 2014
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 60 µg dose hepatitis B vaccine 60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6	Biological: 60 µg dose hepatitis B vaccine; three-dose, 60 µg per dose
Experimental: 20 µg dose hepatitis B vaccine 20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6	Biological: 20 µg dose hepatitis B vaccine; three-dose, 20 µg per dose

Outcome Measures

Primary Outcome Measures

1. Number and Percentage of Participants With Anti-HBs Seroconversion at Month 7 [Month 7]

   The measurements of anti-HBs antibodies were determined quantitatively by CMIA(Chemiluminescent Microparticle Immunoassay ). The accepted protective serum anti-HBs level was ≥10 mIU/ml.

Secondary Outcome Measures

1. Anti-HBs Concentration at Month 7 [Month 7]

   The measurements of anti-HBs antibodies were determined quantitatively by CMIA(Chemiluminescent Microparticle Immunoassay ).

2. Number and Percentage of Participants With Anti-HBs Seroconversion at Month 12 [Month 12]

   The measurements of anti-HBs antibodies were determined quantitatively by CMIA（Chemiluminescent Microparticle Immunoassay）.The accepted protective serum anti-HBs level was ≥10 mIU/ml.

3. Anti-HBs Concentration at Month 12 [Month 12]

   The measurements of anti-HBs antibodies were determined quantitatively by CMIA（Chemiluminescent Microparticle Immunoassay）.

4. Occurrence of Adverse Events After Vaccination [Within 7 days after the vaccination]

   Occurrence of adverse reactions within 7 days after vaccination with the hepatitis B vaccine

5. Occurrence of Adverse Events After Vaccination [Within 28 days after vaccination]

   Occurrence of adverse reactions within 28 days after vaccination with the hepatitis B vaccine

6. Serious Adverse Events (SAE) Occurred During 42 Month [Month 0-42]

   Occurrence of Serious adverse events (SAE) within 42 month after vaccination with the hepatitis B

Other Outcome Measures

1. Number and Percentage of Participants With Anti-HBs High-level Response at Month 7 [Month 7]

   The measurements of anti-HBs antibodies were determined quantitatively by CMIA. and anti-HBs concentrations ≥100 mIU/ml were high-level response.

2. Number and Percentage of Participants With Anti-HBs High-level Response at Month 12 [Month 12]

   The measurements of anti-HBs antibodies were determined quantitatively by CMIA. and anti-HBs concentrations ≥100 mIU/ml were high-level response.

3. Number and Percentage of Participants With Anti-HBs Antibodies at Month 6 Before the Third Injection [Month 6 before the third injection]

   The measurements of anti-HBs antibodies were determined quantitatively by CMIA. The accepted protective serum anti-HBs level was ≥10 mIU/ml.

4. Anti-HBs Concentration at Month 6 Before the Third Injection [Month 6 before the third injection]

   Anti-HBs concentration at month 6 before the third injection as measured by CMIA（Chemiluminescent Microparticle Immunoassay）.

5. Number and Percentage of Participants With Anti-HBs High-level Response at Month 6 Before the Third Injection [Month 6 before the third injection]

   The measurements of anti-HBs antibodies were determined quantitatively by CMIA. and anti-HBs concentrations ≥100 mIU/ml were high-level response.

6. Number and Percentage of Participants With Anti-HBs Seroconversion at Month 42 [Month 42]

   The measurements of anti-HBs antibodies were determined quantitatively by CMIA(Chemiluminescent Microparticle Immunoassay ). The accepted protective serum anti-HBs level was ≥10 mIU/ml.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HIV-infected

• Aged between 18 and 70 years

• Serologically negative for hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) at enrollment

• Willing to adhere to the study protocol

Exclusion Criteria:

• Being pregnant

• Acute cytolysis in the last three months before enrollment

• Any vaccination before or during the month preceding enrollment

• Any Intolerance or allergy to any component of the vaccine

• Ongoing opportunistic infection

• Hematological disorder

• Cancer

• Unexplained fever the week before enrollment

• Immunosuppressive or immunomodulating treatment in the last six months

• Liver disease

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Suping Wang
• Centers for Disease Control and Prevention, China

Investigators

• Principal Investigator: Suping Wang, Shanxi Medical University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Suping Wang, Professor, Shanxi Medical University
• ClinicalTrials.gov Identifier: NCT03316807
• Other Study ID Numbers: 2012ZX10002001003004004
• First Posted: Oct 20, 2017
• Last Update Posted: Mar 11, 2022
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Suping Wang, Professor, Shanxi Medical University: Hepatitis B, Vaccine; Randomized Controlled Trial; HIV; Immunogenicity
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis; Vaccines

Study Results

Participant Flow

Arm/Group Title	60 µg Dose Hepatitis B Vaccine	20 µg Dose Hepatitis B Vaccine
Arm/Group Description	60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 60 µg dose hepatitis B vaccine: three-dose, 60 µg per dose	20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 20 µg dose hepatitis B vaccine: three-dose, 20 µg per dose
Period Title: Overall Study
STARTED	91	91
COMPLETED	60	65
NOT COMPLETED	31	26

Baseline Characteristics

Arm/Group Title	60 µg Dose Hepatitis B Vaccine	20 µg Dose Hepatitis B Vaccine	Total
Arm/Group Description	60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 60 µg dose hepatitis B vaccine: three-dose, 60 µg per dose	20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 20 µg dose hepatitis B vaccine: three-dose, 20 µg per dose	Total of all reporting groups
Overall Participants	91	91	182
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.5 (11.4)	38.2 (10.6)	39.3 (11.1)
Sex: Female, Male (Count of Participants)
Female	42 46.2%	33 36.3%	75 41.2%
Male	49 53.8%	58 63.7%	107 58.8%
Race/Ethnicity, Customized (Count of Participants)
Han ethnicity	32 35.2%	24 26.4%	56 30.8%
Zhuang ethnicity	49 53.8%	62 68.1%	111 61%
others	10 11%	5 5.5%	15 8.2%

Outcome Measures

1. Primary Outcome

Title	Number and Percentage of Participants With Anti-HBs Seroconversion at Month 7
Description	The measurements of anti-HBs antibodies were determined quantitatively by CMIA(Chemiluminescent Microparticle Immunoassay ). The accepted protective serum anti-HBs level was ≥10 mIU/ml.
Time Frame	Month 7

Outcome Measure Data

Analysis Population Description

83 and 82 patients in the IM60（60μg recombinant hepatitis B vaccine） and IM20（20μg recombinant hepatitis B vaccine） groups completed the followed-up at months 7.

Arm/Group Title	60 µg Dose Hepatitis B Vaccine	20 µg Dose Hepatitis B Vaccine
Arm/Group Description	60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 60 µg dose hepatitis B vaccine: three-dose, 60 µg per dose	20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 20 µg dose hepatitis B vaccine: three-dose, 20 µg per dose
Measure Participants	83	82
Count of Participants [Participants]	75 82.4%	69 75.8%

2. Secondary Outcome

Title	Anti-HBs Concentration at Month 7
Description	The measurements of anti-HBs antibodies were determined quantitatively by CMIA(Chemiluminescent Microparticle Immunoassay ).
Time Frame	Month 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	60 µg Dose Hepatitis B Vaccine	20 µg Dose Hepatitis B Vaccine
Arm/Group Description	60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 60 µg dose hepatitis B vaccine: three-dose, 60 µg per dose	20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 20 µg dose hepatitis B vaccine: three-dose, 20 µg per dose
Measure Participants	83	82
Mean (95% Confidence Interval) [mIU/mL]	623.3	469.4

3. Secondary Outcome

Title	Number and Percentage of Participants With Anti-HBs Seroconversion at Month 12
Description	The measurements of anti-HBs antibodies were determined quantitatively by CMIA（Chemiluminescent Microparticle Immunoassay）.The accepted protective serum anti-HBs level was ≥10 mIU/ml.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	60 µg Dose Hepatitis B Vaccine	20 µg Dose Hepatitis B Vaccine
Arm/Group Description	60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 60 µg dose hepatitis B vaccine: three-dose, 60 µg per dose	20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 20 µg dose hepatitis B vaccine: three-dose, 20 µg per dose
Measure Participants	74	68
Count of Participants [Participants]	55 60.4%	50 54.9%

4. Secondary Outcome

Title	Anti-HBs Concentration at Month 12
Description	The measurements of anti-HBs antibodies were determined quantitatively by CMIA（Chemiluminescent Microparticle Immunoassay）.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	60 µg Dose Hepatitis B Vaccine	20 µg Dose Hepatitis B Vaccine
Arm/Group Description	60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 60 µg dose hepatitis B vaccine: three-dose, 60 µg per dose	20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 20 µg dose hepatitis B vaccine: three-dose, 20 µg per dose
Measure Participants	74	68
Mean (95% Confidence Interval) [mIU/ml]	290.4	264.4

5. Secondary Outcome

Title	Occurrence of Adverse Events After Vaccination
Description	Occurrence of adverse reactions within 7 days after vaccination with the hepatitis B vaccine
Time Frame	Within 7 days after the vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	60 µg Dose Hepatitis B Vaccine	20 µg Dose Hepatitis B Vaccine
Arm/Group Description	60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 60 µg dose hepatitis B vaccine: three-dose, 60 µg per dose	20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 20 µg dose hepatitis B vaccine: three-dose, 20 µg per dose
Measure Participants	88	88
pain	5 5.5%	5 5.5%
erythema	6 6.6%	5 5.5%
edema	5 5.5%	4 4.4%
induration	4 4.4%	4 4.4%

6. Secondary Outcome

Title	Occurrence of Adverse Events After Vaccination
Description	Occurrence of adverse reactions within 28 days after vaccination with the hepatitis B vaccine
Time Frame	Within 28 days after vaccination

Outcome Measure Data

Analysis Population Description

Safety analysis was performed on all included participants.

Arm/Group Title	60 µg Dose Hepatitis B Vaccine	20 µg Dose Hepatitis B Vaccine
Arm/Group Description	60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 60 µg dose hepatitis B vaccine: three-dose, 60 µg per dose	20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 20 µg dose hepatitis B vaccine: three-dose, 20 µg per dose
Measure Participants	88	88
fever	1 1.1%	1 1.1%
headache	2 2.2%	1 1.1%

7. Secondary Outcome

Title	Serious Adverse Events (SAE) Occurred During 42 Month
Description	Occurrence of Serious adverse events (SAE) within 42 month after vaccination with the hepatitis B
Time Frame	Month 0-42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	60 µg Dose Hepatitis B Vaccine	20 µg Dose Hepatitis B Vaccine
Arm/Group Description	60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 60 µg dose hepatitis B vaccine: three-dose, 60 µg per dose	20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 20 µg dose hepatitis B vaccine: three-dose, 20 µg per dose
Measure Participants	88	88
Count of Participants [Participants]	0 0%	0 0%

8. Other Pre-specified Outcome

Title	Number and Percentage of Participants With Anti-HBs High-level Response at Month 7
Description	The measurements of anti-HBs antibodies were determined quantitatively by CMIA. and anti-HBs concentrations ≥100 mIU/ml were high-level response.
Time Frame	Month 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	60 µg Dose Hepatitis B Vaccine	20 µg Dose Hepatitis B Vaccine
Arm/Group Description	60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 60 µg dose hepatitis B vaccine: three-dose, 60 µg per dose	20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 20 µg dose hepatitis B vaccine: three-dose, 20 µg per dose
Measure Participants	83	82
Count of Participants [Participants]	62 68.1%	54 59.3%

9. Other Pre-specified Outcome

Title	Number and Percentage of Participants With Anti-HBs High-level Response at Month 12
Description	The measurements of anti-HBs antibodies were determined quantitatively by CMIA. and anti-HBs concentrations ≥100 mIU/ml were high-level response.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	60 µg Dose Hepatitis B Vaccine	20 µg Dose Hepatitis B Vaccine
Arm/Group Description	60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 60 µg dose hepatitis B vaccine: three-dose, 60 µg per dose	20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 20 µg dose hepatitis B vaccine: three-dose, 20 µg per dose
Measure Participants	74	68
Count of Participants [Participants]	34 37.4%	26 28.6%

10. Other Pre-specified Outcome

Title	Number and Percentage of Participants With Anti-HBs Antibodies at Month 6 Before the Third Injection
Description	The measurements of anti-HBs antibodies were determined quantitatively by CMIA. The accepted protective serum anti-HBs level was ≥10 mIU/ml.
Time Frame	Month 6 before the third injection

Outcome Measure Data

Analysis Population Description

83 and 70 patients in the IM60 and IM20 groups completed the followed-up at month 6 before the third injection.

Arm/Group Title	60 µg Dose Hepatitis B Vaccine	20 µg Dose Hepatitis B Vaccine
Arm/Group Description	60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 60 µg dose hepatitis B vaccine: three-dose, 60 µg per dose	20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 20 µg dose hepatitis B vaccine: three-dose, 20 µg per dose
Measure Participants	83	80
Count of Participants [Participants]	65 71.4%	61 67%

11. Other Pre-specified Outcome

Title	Anti-HBs Concentration at Month 6 Before the Third Injection
Description	Anti-HBs concentration at month 6 before the third injection as measured by CMIA（Chemiluminescent Microparticle Immunoassay）.
Time Frame	Month 6 before the third injection

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	60 µg Dose Hepatitis B Vaccine	20 µg Dose Hepatitis B Vaccine
Arm/Group Description	60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 60 µg dose hepatitis B vaccine: three-dose, 60 µg per dose	20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 20 µg dose hepatitis B vaccine: three-dose, 20 µg per dose
Measure Participants	83	80
Mean (95% Confidence Interval) [mIU/ml]	148.9	130.6

12. Other Pre-specified Outcome

Title	Number and Percentage of Participants With Anti-HBs High-level Response at Month 6 Before the Third Injection
Description	The measurements of anti-HBs antibodies were determined quantitatively by CMIA. and anti-HBs concentrations ≥100 mIU/ml were high-level response.
Time Frame	Month 6 before the third injection

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	60 µg Dose Hepatitis B Vaccine	20 µg Dose Hepatitis B Vaccine
Arm/Group Description	60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 60 µg dose hepatitis B vaccine: three-dose, 60 µg per dose	20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 20 µg dose hepatitis B vaccine: three-dose, 20 µg per dose
Measure Participants	83	80
Count of Participants [Participants]	29 31.9%	27 29.7%

13. Other Pre-specified Outcome

Title	Number and Percentage of Participants With Anti-HBs Seroconversion at Month 42
Description	The measurements of anti-HBs antibodies were determined quantitatively by CMIA(Chemiluminescent Microparticle Immunoassay ). The accepted protective serum anti-HBs level was ≥10 mIU/ml.
Time Frame	Month 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	60 µg Dose Hepatitis B Vaccine	20 µg Dose Hepatitis B Vaccine
Arm/Group Description	60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 60 µg dose hepatitis B vaccine: three-dose, 60 µg per dose	20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 20 µg dose hepatitis B vaccine: three-dose, 20 µg per dose
Measure Participants	60	65
Count of Participants [Participants]	31 34.1%	29 31.9%

Adverse Events

Arm/Group Title	60 µg Dose Hepatitis B Vaccine		20 µg Dose Hepatitis B Vaccine
Arm/Group Description	60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 60 µg dose hepatitis B vaccine: three-dose, 60 µg per dose		20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 20 µg dose hepatitis B vaccine: three-dose, 20 µg per dose
All Cause Mortality
	60 µg Dose Hepatitis B Vaccine		20 µg Dose Hepatitis B Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/88 (0%)		0/88 (0%)
Serious Adverse Events
	60 µg Dose Hepatitis B Vaccine		20 µg Dose Hepatitis B Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/88 (0%)		0/88 (0%)
Other (Not Including Serious) Adverse Events
	60 µg Dose Hepatitis B Vaccine		20 µg Dose Hepatitis B Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/88 (9.1%)		6/88 (6.8%)
Musculoskeletal and connective tissue disorders
Pain	5/88 (5.7%)		5/88 (5.7%)
Skin and subcutaneous tissue disorders
erythema	6/88 (6.8%)		5/88 (5.7%)
edema	5/88 (5.7%)		4/88 (4.5%)
induration	4/88 (4.5%)		4/88 (4.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.