Effectiveness of Two Hepatitis B Vaccines in HIV-negative Youths

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00107042
First received: April 4, 2005
Last updated: June 23, 2014
Last verified: April 2014
Results First Received: September 5, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Single Blind (Subject);   Primary Purpose: Prevention
Condition: Hepatitis B
Interventions: Biological: Recombivax
Biological: Twinrix

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was started in February 2004 and was completed in July 2008. A total of 11 sites, all in the United States and Puerto Rico, participated in the study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Recombivax Active Comparator: 1st dose at Week 0, 2nd dose at Week 24
Twinrix Experimental: 1st dose at Week 0, 2nd dose at Week 24

Participant Flow:   Overall Study
    Recombivax     Twinrix  
STARTED     60     63  
COMPLETED     38     47  
NOT COMPLETED     22     16  
Lost to Follow-up                 9                 7  
Withdrawal by Subject                 6                 1  
Moved out of area                 5                 3  
Pregnancy                 1                 1  
Inadvertent enrollment                 0                 1  
vaccinated outside window                 1                 1  
Disallowed medications                 0                 2  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Recombivax Active Comparator: 1st dose at Week 0, 2nd dose at Week 24
Twinrix Experimental: 1st dose at Week 0, 2nd dose at Week 24
Total Total of all reporting groups

Baseline Measures
    Recombivax     Twinrix     Total  
Number of Participants  
[units: participants]
  60     63     123  
Age  
[units: years]
Mean ± Standard Deviation
  15.02  ± 1.43     15.22  ± 1.71     15.12  ± 1.58  
Age, Customized  
[units: participants]
     
12 - 14 years     18     23     41  
15 - 17 years     42     40     82  
Gender  
[units: participants]
     
Female     19     27     46  
Male     41     36     77  
Race (NIH/OMB)  
[units: participants]
     
American Indian or Alaska Native     0     0     0  
Asian     0     0     0  
Native Hawaiian or Other Pacific Islander     0     0     0  
Black or African American     20     14     34  
White     3     6     9  
More than one race     37     43     80  
Unknown or Not Reported     0     0     0  



  Outcome Measures
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1.  Primary:   Qualitative Seroresponsiveness to Hepatitis B Surface Antigen   [ Time Frame: Week (Wk) 28 (One month after the second immunization) ]

2.  Primary:   Safety and Tolerability of Vaccine Regimens of Recombivax and Twinrix (Number of Participants With >=1 Adverse Event (AE))   [ Time Frame: Week 12, Week 24, Week 28, Week 76 ]

3.  Primary:   Safety and Tolerability of Vaccine Regimens of Recombivax and Twinrix: Serious Adverse Events (SAE)(Number of Subjects With >= 1 SAE)   [ Time Frame: Week 12, Week 24, Week 28, Week 76 ]

4.  Secondary:   Quantitative Vaccine Response   [ Time Frame: Week 28 ]
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Measure Type Secondary
Measure Title Quantitative Vaccine Response
Measure Description The Log10 titer was used as the quantitative vaccine response.
Time Frame Week 28  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects who had a wk 28 Hep B a'body titer and was no more than 8 wks after the 2nd vaccination were included. 1 subject was missing wk 28 titer. The a'body at week 48 was positive, so subject was treated as a responder for the binary measure. For the continuous a'body titer, the exact number could not be assumed; subject was treated as missing.

Reporting Groups
  Description
Recombivax Active Comparator: 1st dose at Week 0, 2nd dose at Week 24
Twinrix Experimental: 1st dose at Week 0, 2nd dose at Week 24

Measured Values
    Recombivax     Twinrix  
Number of Participants Analyzed  
[units: participants]
  47     54  
Quantitative Vaccine Response  
[units: Log10¬†titer¬†(mIU/ml)]
Mean ± Standard Deviation
  2.29  ± 0.82     2.58  ± 0.65  


Statistical Analysis 1 for Quantitative Vaccine Response
Groups [1] All groups
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.0608
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Analysis included an assessment of quantitative titer values in each of the two arms using confidence intervals and examining the frequency distributions of the titers in each arm. Transformations were considered (log10) for the titers based on the distributional properties observed in the sample, with the goal of attaining approximate normality of the transformed data.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.

Statistical Analysis 2 for Quantitative Vaccine Response
Groups [1] Recombivax
Method [2] 95% confidence interval
Mean response [3] 2.29
95% Confidence Interval ( 2.05 to 2.53 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Two-sided confidence intervals (CI) were calculated for both the "Recombivax" and "Twinrix" arms. The CI for the "Recombivax" arm is presented here.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Quantitative Vaccine Response
Groups [1] Twinrix
Method [2] 95% confidence interval
Response rate [3] 2.58
95% Confidence Interval ( 2.40 to 2.76 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Two-sided confidence intervals (CI) were calculated for both the "Recombivax" and "Twinrix" arms. The CI for the "Twinrix" arm is presented here.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



5.  Secondary:   Unadjusted Relationship of Hepatitis B Vaccine Response (Log10 Titer) and Potential Impact Factors Among Subjects Whose Week 28 Antibody Results Are Within Week 28 Visit Window.   [ Time Frame: Week 28 ]

6.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen (Binary); Predictor: STUDY ARM.   [ Time Frame: Week 28 ]

7.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: SITE EFFECT   [ Time Frame: Week 28 ]

8.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: AGE   [ Time Frame: Week 28 ]

9.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: GENDER   [ Time Frame: Week 28 ]

10.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: HISPANIC ETHNICITY   [ Time Frame: Week 28 ]

11.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: RACE   [ Time Frame: Week 28 ]

12.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TANNER STAGE FOR FEMALES   [ Time Frame: Week 28 ]

13.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TANNER STAGE FOR MALES   [ Time Frame: Week 28 ]

14.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: BMI at Baseline   [ Time Frame: Week 28 ]

15.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER SMOKED CIGARETTES   [ Time Frame: Week 28 ]

16.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: SEXUAL IDENTITY   [ Time Frame: Week 28 ]

17.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: AGE AT WHICH SUBJECT FIRST HAD SEX (NOT FORCED)   [ Time Frame: Week 28 ]

18.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TOTAL LIFETIME SEX PARTNERS   [ Time Frame: Week 28 ]

19.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TOTAL LIFETIME MALE SEX PARTNERS   [ Time Frame: Week 28 ]

20.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TOTAL LIFETIME FEMALE SEX PARTNERS   [ Time Frame: Week 28 ]

21.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER DRANK ALCOHOL   [ Time Frame: Week 28 ]

22.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER SMOKED MARIJUANA   [ Time Frame: Week 28 ]

23.  Secondary:   Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER USED DRUGS NOT PRESCRIBE   [ Time Frame: Week 28 ]

24.  Secondary:   Immunogenicity to Hep B 18 Months After First Immunization   [ Time Frame: Week 76 ]

25.  Secondary:   Immunogenicity to Hep A in the Twinrix Arm: One Month Post 2nd Vaccination   [ Time Frame: Week 28 ]

26.  Secondary:   Immunogenicity to Hep A in Twinrix Arm: Twelve Months Post 2nd Vaccination   [ Time Frame: Week 76 ]

27.  Secondary:   Immunogenicity to Hep A in Twinrix Arm: Overall Response (1-month or 12-month After 2nd Vaccination)   [ Time Frame: Week 28 and Week 76 ]

28.  Secondary:   As Treated Analysis – Adequate Antibody Response to Hep B Surface Antigen   [ Time Frame: Week 28 ]

29.  Secondary:   Assessment of Youth Understanding of Vaccine Trial and Informed Consent   [ Time Frame: Screening ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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