Immunogenicity of Hepatitis B Vaccination Among Drug Users

• Sponsor: Shanxi Medical University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02959775
• Collaborator: Centers for Disease Control and Prevention, China (Other)
• Enrollment: 480
• Arms: 3
• Actual Duration (Months): 14

Study Details

Study Description

Brief Summary

Uptake, adherence, and completion of vaccination among drug users 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 drug users from HBV infection.

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

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

Detailed Description

Comparison of 2 vaccination strategy against Hepatitis B in Drug Users

Intervention:

Arm 1 : Receive three intramuscular injections of 60 µg recombinant hepatitis B vaccine at months 0, 1 and 6;

Arm 2 : Receive three intramuscular injections of 20 µg recombinant hepatitis B vaccine at months 0, 1 and 6;

Arm 3 : Receive no vaccination during the study period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 480 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety of High-dose Hepatitis B Vaccine Among Drug Users: a Randomized, Controlled Trial
• Actual Study Start Date: Aug 1, 2014
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 60 µg dose hepatitis B vaccine Receive three intramuscular injections of 60 µg recombinant hepatitis B vaccine 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 Receive three intramuscular injections of 20 µg recombinant hepatitis B vaccine at months 0, 1 and 6	Biological: 20 µg dose hepatitis B vaccine; three-dose, 20 µg per dose
No Intervention: Control Receive no vaccination during the study period

Outcome Measures

Primary Outcome Measures

1. Number and Rate 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. Anti-HBs Concentration at Month 12 [Month 12]

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

3. Number and Rate 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.

4. Occurrence of Adverse Events After Vaccination [Within 7 days after the vaccination, at Month 0, 1, and 6]

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

5. Occurrence of Adverse Events After Vaccination [Within 28 days after the vaccination, at Month 0, 1, and 6]

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

6. Serious Adverse Events (SAE) Occurred During Month 12 [Month 0-12]

Other Outcome Measures

1. Number and Rate 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 Rate 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. 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 by CMIA

4. Number and Rate of Participants With Anti-HBs Seroconversion 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.

5. Number and Rate 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.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Aged between 18 and 70 years at the enrolment

• current illicit drug users before drug rehabilitation

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

• having spent acute physiological detoxification phase

Exclusion Criteria:

• any intolerance or allergy to any component of the vaccine

• ongoing opportunistic infection

• liver disease

• hemopathy

• cancer

• unexplained fever in the last week before the recruiting

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Shanxi Medical University
• 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: NCT02959775
• Other Study ID Numbers: 2012ZX10002001003004002
• First Posted: Nov 9, 2016
• Last Update Posted: Feb 18, 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 vaccination; Immunogenicity; Randomized controlled trial; Drug abuse
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis; Vaccines

Study Results

Participant Flow

Arm/Group Title	IM20 Group	IM60 Group	Blank Control Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received no intervention.
Period Title: Overall Study
STARTED	160	160	160
COMPLETED	133	133	124
NOT COMPLETED	27	27	36

Baseline Characteristics

Arm/Group Title	IM20 Group	IM60 Group	Blank Control Group	Total
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received no intervention.	Total of all reporting groups
Overall Participants	160	160	160	480
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.0 (8.7)	36.4 (8.6)	36.7 (8.3)	36.7 (8.5)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	160 100%	160 100%	160 100%	480 100%
Race/Ethnicity, Customized (Count of Participants)
Han ethnicity	158 98.8%	158 98.8%	158 98.8%	474 98.8%
minority ethnicity	2 1.3%	2 1.3%	2 1.3%	6 1.3%
Region of Enrollment (Count of Participants)
Urban	67 41.9%	62 38.8%	69 43.1%	198 41.3%
Rural	93 58.1%	98 61.3%	91 56.9%	282 58.8%

Outcome Measures

1. Primary Outcome

Title	Number and Rate 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

Exclusion of participants who did not received/competed vaccine or left the centers.150, 149 and 151 patients in the IM20, IM60 and blank control groups completed the followed-up at months 7 .

Arm/Group Title	IM20 Group	IM60 Group	Blank Control Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received no intervention
Measure Participants	150	149	151
Count of Participants [Participants]	142 88.8%	138 86.3%	0 0%

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	IM20 Group	IM60 Group	Blank Control Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received no intervention.
Measure Participants	150	149	151
Mean (95% Confidence Interval) [mIU/mL]	909.6	2022.5	0.3

3. 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

133, 133 and 124 patients in the IM20, IM60 and blank control groups completed the followed-up at months 12 .

Arm/Group Title	IM20 Group	IM60 Group	Control
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received no intervention.
Measure Participants	133	133	124
Mean (95% Confidence Interval) [mIU/mL]	470.5	676.7	0.3

4. Secondary Outcome

Title	Number and Rate 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

133, 133 and 124 patients in the IM20, IM60 and blank control groups completed the followed-up at months 12.

Arm/Group Title	IM20 Group	IM60 Group	Blank Control Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received no intervention
Measure Participants	133	133	124
Count of Participants [Participants]	119 74.4%	122 76.3%	0 0%

5. Secondary Outcome

Title	Occurrence of Adverse Events After Vaccination
Description	Occurrence of adverse reactions within 7 days after vaccination with the hepatitis B
Time Frame	Within 7 days after the vaccination, at Month 0, 1, and 6

Outcome Measure Data

Analysis Population Description

158 participants in the IM20 group and 156 in the IM60 group received the first injection. The blank control group was not vaccinated with hepatitis B vaccine, so adverse reactions of hepatitis B vaccine were not collected and analyzed.

Arm/Group Title	IM20 Group	IM60 Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	158	156
Count of Participants [Participants]	14 8.8%	13 8.1%

6. Secondary Outcome

Title	Occurrence of Adverse Events After Vaccination
Description	Occurrence of adverse reactions within 28 days after vaccination with the hepatitis B
Time Frame	Within 28 days after the vaccination, at Month 0, 1, and 6

Outcome Measure Data

Analysis Population Description

The blank control group was not vaccinated with hepatitis B vaccine, so adverse reactions of hepatitis B vaccine were not collected and analyzed.

Arm/Group Title	IM20 Group	IM60 Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	158	156
Count of Participants [Participants]	2 1.3%	2 1.3%

7. Secondary Outcome

Title	Serious Adverse Events (SAE) Occurred During Month 12
Time Frame	Month 0-12

Outcome Measure Data

Analysis Population Description

The blank control group was not vaccinated with hepatitis B vaccine, so adverse reactions of hepatitis B vaccine were not collected and analyzed.

Arm/Group Title	IM20 Group	IM60 Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	133	133
Count of Participants [Participants]	0 0%	0 0%

8. Other Pre-specified Outcome

Title	Number and Rate 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	IM20 Group	IM60 Group	Blank Control Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received no intervention
Measure Participants	150	149	151
Count of Participants [Participants]	111 69.4%	116 72.5%	0 0%

9. Other Pre-specified Outcome

Title	Number and Rate 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	IM20 Group	IM60 Group	Blank Control Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received no intervention
Measure Participants	133	133	124
Count of Participants [Participants]	73 45.6%	91 56.9%	0 0%

10. 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 by CMIA
Time Frame	Month 6 before the third injection

Outcome Measure Data

Analysis Population Description

155 and 150 patients in the IM20 and IM60 groups completed the followed-up at months 6 before the third injection.

Arm/Group Title	IM20 Group	IM60 Group	Blank Control Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received no intervention.
Measure Participants	155	150	151
Mean (95% Confidence Interval) [mIU/mL]	126.3	524.5	0.3

11. Other Pre-specified Outcome

Title	Number and Rate of Participants With Anti-HBs Seroconversion 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

[Not Specified]

Arm/Group Title	IM20 Group	IM60 Group	Blank Control Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received no intervention.
Measure Participants	155	150	151
Count of Participants [Participants]	98 61.3%	109 68.1%	0 0%

12. Other Pre-specified Outcome

Title	Number and Rate 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	IM20 Group	IM60 Group	Blank Control Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received no intervention.
Measure Participants	155	150	151
Count of Participants [Participants]	27 16.9%	44 27.5%	0 0%

Adverse Events

Adverse Event Reporting Description	The blank control group was not vaccinated with hepatitis B vaccine, so adverse reactions of hepatitis B vaccine were not collected and analyzed.
Arm/Group Title	IM20 Group		IM60 Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.		Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
All Cause Mortality
	IM20 Group		IM60 Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/158 (0%)		0/156 (0%)
Serious Adverse Events
	IM20 Group		IM60 Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/158 (0%)		0/156 (0%)
Other (Not Including Serious) Adverse Events
	IM20 Group		IM60 Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/158 (7.6%)		11/156 (7.1%)
Musculoskeletal and connective tissue disorders
pain	10/158 (6.3%)		9/156 (5.8%)
Skin and subcutaneous tissue disorders
erytherma	8/158 (5.1%)		9/156 (5.8%)

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.