Live Zoster Vaccine in HIV-Infected Adults on Antiretroviral Therapy

This study has been completed.
Sponsor:
Collaborators:
Adult AIDS Clinical Trials Group
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00851786
First received: February 25, 2009
Last updated: February 20, 2014
Last verified: February 2014
Results First Received: September 7, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Prevention
Conditions: Herpes Zoster
HIV Infections
Interventions: Biological: ZOSTAVAX
Biological: Placebo

  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 first person was accrued on 04/29/2009. Accrual in the high CD4 stratum was closed in 02/2010 (n=203; 152 on ZOSTAVAX and 51 on placebo). Accrual to the low CD4 stratum proceeded more slowly with the last subject enrolled on 06/30/2011 (n=192; 144 on ZOSTAVAX and 48 on placebo). All 43 participating sites enrolled at least 1 subject.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Enrollment took place in two stages: Stage I were to enroll 48 subjects (24 in the low CD4 stratum and 24 in the high CD4 stratum). Subjects were randomized 3:1 to receive ZOSTAVAX or placebo. Stage II were to enroll approximately 352 subjects who would be randomized and stratified according to the same schedule.

Reporting Groups
  Description
ZOSTAVAX Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-349 cells/uL vs. >=350 cells/uL), will be given one dose of ZOSTAVAX (Zoster Vaccine Live) at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination after which a safety assessment will be conducted.
Placebo Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-<349 cells/uL vs. >=350 cells/uL), will be given one dose of placebo at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination afer which a safety assessment will be conducted

Participant Flow:   Overall Study
    ZOSTAVAX     Placebo  
STARTED     296 [1]   99 [2]
COMPLETED     291     97  
NOT COMPLETED     5     2  
Withdrawal by Subject                 0                 1  
Protocol Violation                 0                 1  
Lost to Follow-up                 1                 0  
Incarceration                 1                 0  
Site Closure                 1                 0  
Cannot Adhere to Protocol Requirement                 2                 0  
[1] One subject cannot adhere to protocol requirement and was off study with no vaccine.
[2] Two subjects (one found ineligible and one withdrew consent) were off study with no vaccine.



  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
ZOSTAVAX Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-349 cells/uL vs. >=350 cells/uL), will be given one dose of ZOSTAVAX (Zoster Vaccine Live) at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination after which a safety assessment will be conducted.
Placebo Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-<349 cells/uL vs. >=350 cells/uL), will be given one dose of placebo at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination afer which a safety assessment will be conducted
Total Total of all reporting groups

Baseline Measures
    ZOSTAVAX     Placebo     Total  
Number of Participants  
[units: participants]
  296     99     395  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     285     94     379  
>=65 years     11     5     16  
Age  
[units: years]
Median ( Inter-Quartile Range )
  49  
  ( 44 to 56 )  
  49  
  ( 44 to 55 )  
  49  
  ( 44 to 56 )  
Gender  
[units: participants]
     
Female     44     18     62  
Male     252     81     333  
Race/Ethnicity, Customized  
[units: participants]
     
White Non-Hispanic     141     44     185  
Black Non-Hispanic     90     26     116  
Hispanic (regardless of race)     60     27     87  
Asian, Pacific islander     1     1     2  
American Indian, Alaskan Native     2     1     3  
More than one race     1     0     1  
Unknown/missing     1     0     1  
IV drug history  
[units: participants]
     
Never     244     86     330  
Previously     52     13     65  
Nadir CD4  
[units: cells/µL]
Median ( Inter-Quartile Range )
  197  
  ( 109 to 287 )  
  178  
  ( 104.5 to 285 )  
  188  
  ( 108 to 287 )  
Screen CD4  
[units: cells/µL]
Median ( Inter-Quartile Range )
  373  
  ( 286 to 634.5 )  
  353  
  ( 278 to 561 )  
  372  
  ( 286 to 606 )  
Entry CD4  
[units: cells/µL]
Median ( Inter-Quartile Range )
  399  
  ( 282 to 607 )  
  362  
  ( 276 to 579 )  
  394  
  ( 281 to 605 )  
HIV-1 RNA  
[units: log10┬ácopies/mL]
Median ( Inter-Quartile Range )
  1.68  
  ( 1.68 to 1.70 )  
  1.68  
  ( 1.68 to 1.70 )  
  1.68  
  ( 1.68 to 1.70 )  
Prior History of AIDS  
[units: participants]
     
Yes     288     97     385  
No     8     2     10  
History of Chickenpox  
[units: participants]
     
>5 years     219     77     296  
Zoster/no Chickpox     17     7     24  
None     60     15     75  
History of most recent Zoster  
[units: participants]
     
0-1 year     2     1     3  
>1-2 years     13     1     14  
>2-5 years     23     7     30  
>5 years     65     22     87  
None     193     68     261  
Duration from Historary Retinal Necrosis  
[units: participants]
     
>5 years     2     0     2  
None     294     99     393  



  Outcome Measures
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1.  Primary:   Number of Participants With Composite Safety Endpoint of the Occurrence of Serious Adverse Events (SAEs) or Division of AIDS (DAIDS) Grade 3 and 4 Signs and Symptoms, Excluding SAEs Related to Trauma   [ Time Frame: During the 6 week study period after receipt of any dose of ZOSTAVAX ]

2.  Secondary:   VZV Antibodies as Measured by gpELISA   [ Time Frame: Within 6 weeks following one or two doses of ZOSTAVAX ]

3.  Secondary:   VZV-specific Cellular Immune Responses by Intracellular Cytokine Staining and/or ELISPOT Assays in the First 40 Subjects Entering in Each CD4 Stratum at the Opening of Stage II   [ Time Frame: Within 6 weeks following one or two doses of ZOSTAVAX ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: Clinicaltrials.gov Coordinator
Organization: Center for Biostatistics in AIDS Research, Harvard School of Public Health
phone: (617) 432-2829
e-mail: CBAR.ClinicalTrials.Gov@sdac.harvard.edu


Publications:


Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00851786     History of Changes
Other Study ID Numbers: A5247, 10519, ACTG A5247
Study First Received: February 25, 2009
Results First Received: September 7, 2012
Last Updated: February 20, 2014
Health Authority: United States: Food and Drug Administration