Live Zoster Vaccine in HIV-Infected Adults on Antiretroviral Therapy
A Phase II, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety, Tolerability, and Immunogenicity of ZOSTAVAX® (Zoster Vaccine Live) in Human Immunodeficiency Virus (HIV)-1-Infected Adults on Potent Combination ART With Conserved Immune Function
3 other identifiers
interventional
395
1 country
43
Brief Summary
Herpes zoster, or shingles, is the result of a viral infection that causes a painful skin rash, usually in older people or people with suppressed immune systems like those infected with HIV. The ZOSTAVAX vaccine has been shown to reduce the number of infections and symptoms of herpes zoster infection in people over the age of 60. The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of two doses of ZOSTAVAX in HIV-1-infected adults with conserved immune function (Cd4+ T cell counts \>=200 cells/uL) virologically suppressed on potent combination antiretroviral therapy (ART).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Apr 2009
43 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 25, 2009
CompletedFirst Posted
Study publicly available on registry
February 26, 2009
CompletedStudy Start
First participant enrolled
April 29, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 22, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
January 3, 2012
CompletedResults Posted
Study results publicly available
October 10, 2012
CompletedNovember 4, 2021
January 1, 2018
2.4 years
February 25, 2009
September 7, 2012
November 2, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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
Although the study was designed as a randomized trial, it was not powered to detect safety related differences between treatment arms. The safety of ZOSTAVAX was determined by comparing the number of subjects from the active arm who experienced safety endpoint to the number from a pre-specified decision rule, which was calculated based on a similar population and calibrated using the number of safety endpoints observed from the placebo arm. The pre-specified decision rule is that ZOSTAVAX would be considered to have acceptable safety if no more than 18 subjects experience a study-defined composite safety endpoint.
During the 6 week study period after receipt of any dose of ZOSTAVAX
Secondary Outcomes (2)
VZV Antibodies as Measured by gpELISA
Within 6 weeks following one or two doses of ZOSTAVAX
Geometric Mean Fold Rise (GMFR) in VZV ELISpot Responses
Entry, Week 6, Week 12
Study Arms (2)
1
EXPERIMENTALParticipants with CD4 cell counts of 200 cells/uL or greater in Stages 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.
2
PLACEBO COMPARATORParticipants with CD4 cell counts of 200 cells/uL or greater in Stages 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 after which a safety assessment will be conducted
Interventions
Eligibility Criteria
You may qualify if:
- HIV infected
- Use of potent combination ART regimen within 90 days prior to entry and undetectable plasma HIV RNA level within 90-210 days prior to study entry
- CD4 cell count of at least 200 cells/uL obtained within 30 days prior to study entry
- Laboratory values obtained within 90 days prior to study entry
- Hemoglobin 7.0 g/dL or greater
- Platelet count 50,000/mm3 or greater
- Creatinine 3 x ULN or less
- AST (SGOT), ALT (SGPT), and alkaline phosphatase 5 x ULN or less
- For females of reproductive potential, a negative serum or urine pregnancy test within 24 hours prior to study entry
- Willing to use accepted forms of contraception for the duration of the study
- History of varicella or herpes zoster more than 1 year prior to vaccination or VZV seropositivity at any time prior to entry
- Men and women age \>=18 years
- Ability and willingness of subject or legal guardian/representative to provide informed consent
You may not qualify if:
- History of nadir CD4+ count \<100 cells/uL
- Known or suspected immune dysfunction caused by a medical condition or any cause other than HIV infection, such as congenital immunodeficiency, organ or bone marrow transplantation, leukemia, lymphoma, Hodgkin's disease, multiple myeloma, or generalized malignancy \[NOTE: Subjects with prostate or breast cancer who are not on chemotherapeutic drugs (other than hormone blocking drugs), subjects with skin cancer or Kaposi's sarcoma limited to skin who are not receiving radiation therapy or chemotherapy, and subjects with a history of other malignancies who have been disease-free for at least 5 years will be eligible for enrollment.\]
- Receipt of any varicella or zoster vaccine prior to study entry
- History of allergy/sensitivity, or hypersensitivity to any vaccine component, including gelatin or neomycin
- Receipt of immunoglobulin or any blood products, other than autologous blood transfusion, given during the 5 months prior to study entry or expected during the 24-week study period
- Receipt of any live virus vaccine within 28 days prior to study entry or during study period
- Receipt of any inactivated vaccine within 7 days prior to study entry or during study period
- Scheduled administration of any live virus vaccine or inactivated vaccine at or between study entry and the Week 12 visit
- Participation in an investigational drug study within the last 30 days prior to study entry
- Use of immunosuppressive therapy. More information can be found in the protocol.
- Any chronic suppressive antiviral therapy with activity against herpes viruses, including but not limited to acyclovir, famciclovir, valacyclovir, ganciclovir, foscarnet, and cidofovir within 7 days prior to study entry or expected use through the 24-week study period except where necessary for acute treatment of intercurrent viral infection.
- Any episode of VZV reactivation in the 12 months prior to study entry
- Active drug or alcohol use, dependence, or any other reason that, in the opinion of the site investigator, would interfere with the study
- Pregnancy (including subjects who are expecting to conceive within 3 months of the second vaccination) or breast feeding
- Any acute intercurrent illness that might interfere with the interpretation of the study
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (43)
Alabama Therapeutics CRS
Birmingham, Alabama, 35294-2050, United States
University of Southern California CRS
Los Angeles, California, 90033, United States
UCLA CARE Center CRS
Los Angeles, California, 90035, United States
Stanford CRS
Palo Alto, California, 94304-5350, United States
Ucsd, Avrc Crs
San Diego, California, 92103, United States
Ucsf Aids Crs
San Francisco, California, 94110, United States
Harbor-UCLA Med. Ctr. CRS
Torrance, California, 90502, United States
University of Colorado Hospital CRS
Aurora, Colorado, 80045, United States
Denver Public Health CRS
Denver, Colorado, 80204, United States
Georgetown University CRS (GU CRS)
Washington D.C., District of Columbia, 20007, United States
Univ. of Miami AIDS CRS
Miami, Florida, 33136, United States
The Ponce de Leon Center CRS
Atlanta, Georgia, 30308-2012, United States
Northwestern University CRS
Chicago, Illinois, 60611, United States
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, 60612, United States
IHV Baltimore Treatment CRS
Baltimore, Maryland, 21201, United States
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, 02114, United States
Brigham and Women's Hosp. ACTG CRS
Boston, Massachusetts, 02115, United States
Bmc Actg Crs
Boston, Massachusetts, 02118, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, 02215, United States
Henry Ford Hosp. CRS
Detroit, Michigan, 48202, United States
Washington U CRS
St Louis, Missouri, 63110, United States
Cooper Univ. Hosp. CRS
Camden, New Jersey, 08103, United States
New Jersey Medical School- Adult Clinical Research Ctr. CRS
Newark, New Jersey, 07103, United States
Cornell CRS
New York, New York, 10010, United States
NY Univ. HIV/AIDS CRS
New York, New York, 10016, United States
HIV Prevention & Treatment CRS
New York, New York, 10032, United States
Univ. of Rochester ACTG CRS
Rochester, New York, 14642, United States
Bronx-Lebanon Hosp. Ctr. CRS
The Bronx, New York, 10457, United States
Chapel Hill CRS
Chapel Hill, North Carolina, 27599, United States
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, 27710, United States
Greensboro CRS
Greensboro, North Carolina, 27401, United States
Univ. of Cincinnati CRS
Cincinnati, Ohio, 45267-0405, United States
Case CRS
Cleveland, Ohio, 44106, United States
MetroHealth CRS
Cleveland, Ohio, 44109, United States
The Ohio State University Medical Center
Columbus, Ohio, 43210, United States
The Research & Education Group-Portland CRS
Portland, Oregon, 97210, United States
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, 19104, United States
Thomas Jefferson Univ. Med. Ctr. CRS
Philadelphia, Pennsylvania, 19107, United States
Pitt CRS
Pittsburgh, Pennsylvania, 15213-2582, United States
The Miriam Hosp. ACTG CRS
Providence, Rhode Island, 02906, United States
Vanderbilt Therapeutics CRS
Nashville, Tennessee, 37204, United States
University of Washington AIDS CRS
Seattle, Washington, 98104, United States
Related Publications (6)
Gebo KA, Kalyani R, Moore RD, Polydefkis MJ. The incidence of, risk factors for, and sequelae of herpes zoster among HIV patients in the highly active antiretroviral therapy era. J Acquir Immune Defic Syndr. 2005 Oct 1;40(2):169-74. doi: 10.1097/01.qai.0000178408.62675.b0.
PMID: 16186734BACKGROUNDGilderman LI, Lawless JF, Nolen TM, Sterling T, Rutledge RZ, Fernsler DA, Azrolan N, Sutradhar SC, Wang WW, Chan IS, Schlienger K, Schodel F, Silber JL; Zostavax Protocol 010 Study Group. A double-blind, randomized, controlled, multicenter safety and immunogenicity study of a refrigerator-stable formulation of Zostavax. Clin Vaccine Immunol. 2008 Feb;15(2):314-9. doi: 10.1128/CVI.00310-07. Epub 2007 Dec 12.
PMID: 18077611BACKGROUNDHolcomb K, Weinberg JM. A novel vaccine (Zostavax) to prevent herpes zoster and postherpetic neuralgia. J Drugs Dermatol. 2006 Oct;5(9):863-6.
PMID: 17039651BACKGROUNDOxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, Arbeit RD, Simberkoff MS, Gershon AA, Davis LE, Weinberg A, Boardman KD, Williams HM, Zhang JH, Peduzzi PN, Beisel CE, Morrison VA, Guatelli JC, Brooks PA, Kauffman CA, Pachucki CT, Neuzil KM, Betts RF, Wright PF, Griffin MR, Brunell P, Soto NE, Marques AR, Keay SK, Goodman RP, Cotton DJ, Gnann JW Jr, Loutit J, Holodniy M, Keitel WA, Crawford GE, Yeh SS, Lobo Z, Toney JF, Greenberg RN, Keller PM, Harbecke R, Hayward AR, Irwin MR, Kyriakides TC, Chan CY, Chan IS, Wang WW, Annunziato PW, Silber JL; Shingles Prevention Study Group. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005 Jun 2;352(22):2271-84. doi: 10.1056/NEJMoa051016.
PMID: 15930418BACKGROUNDVafai A, Berger M. Zoster in patients infected with HIV: a review. Am J Med Sci. 2001 Jun;321(6):372-80. doi: 10.1097/00000441-200106000-00003.
PMID: 11417752BACKGROUNDBenson CA, Andersen JW, Macatangay BJC, Mailliard RB, Rinaldo CR Jr, Read S, Bozzolo DR, Purdue L, Jennings C, Keefer MC, Glesby M, Tebas P, Russell AF, Martin J, Annunziato P, Popmihajlov Z, Lennox JL. Safety and Immunogenicity of Zoster Vaccine Live in Human Immunodeficiency Virus-Infected Adults With CD4+ Cell Counts >200 Cells/mL Virologically Suppressed on Antiretroviral Therapy. Clin Infect Dis. 2018 Nov 13;67(11):1712-1719. doi: 10.1093/cid/ciy242.
PMID: 29590326DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- ACTG Clinicaltrials.gov Coordinator
- Organization
- ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Study Officials
- STUDY CHAIR
Constance A. Benson, MD
University of California, San Diego
- STUDY CHAIR
Jeffrey L. Lennox, MD
Emory University
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 25, 2009
First Posted
February 26, 2009
Study Start
April 29, 2009
Primary Completion
September 22, 2011
Study Completion
January 3, 2012
Last Updated
November 4, 2021
Results First Posted
October 10, 2012
Record last verified: 2018-01