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Herpes ZosterPhase 2NCT00851786

Live Zoster Vaccine in HIV-Infected Adults on Antiretroviral Therapy

A Phase 2 study testing ZOSTAVAX in people with Herpes Zoster and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 43 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Herpes Zoster, HIV Infections
What is being tested?
ZOSTAVAX
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
395 participants
Where
43 sitesUnited States
Study dates
29 Apr 2009to 3 Jan 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 13Show fewer
  • 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

Who cannot join

  • 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
Show all 16Show fewer
  • 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
  • Significant underlying illness preventing completion of the study

Trial locations and contacts

43 sites in 1 country.

43 sites in 1 country

United States43 sites

  • The Ponce de Leon Center CRS

    Atlanta, Georgia, 30308-2012

  • University of Colorado Hospital CRS

    Aurora, Colorado, 80045

  • IHV Baltimore Treatment CRS

    Baltimore, Maryland, 21201

  • Johns Hopkins Adult AIDS CRS

    Baltimore, Maryland, 21287

  • Alabama Therapeutics CRS

    Birmingham, Alabama, 35294-2050

  • Massachusetts General Hospital ACTG CRS

    Boston, Massachusetts, 02114

  • Brigham and Women's Hosp. ACTG CRS

    Boston, Massachusetts, 02115

  • Bmc Actg Crs

    Boston, Massachusetts, 02118

  • Beth Israel Deaconess Med. Ctr., ACTG CRS

    Boston, Massachusetts, 02215

  • Cooper Univ. Hosp. CRS

    Camden, New Jersey, 08103

  • Chapel Hill CRS

    Chapel Hill, North Carolina, 27599

  • Northwestern University CRS

    Chicago, Illinois, 60611

  • Rush Univ. Med. Ctr. ACTG CRS

    Chicago, Illinois, 60612

  • Univ. of Cincinnati CRS

    Cincinnati, Ohio, 45267-0405

  • Case CRS

    Cleveland, Ohio, 44106

  • MetroHealth CRS

    Cleveland, Ohio, 44109

  • The Ohio State University Medical Center

    Columbus, Ohio, 43210

  • Denver Public Health CRS

    Denver, Colorado, 80204

  • Henry Ford Hosp. CRS

    Detroit, Michigan, 48202

  • Duke Univ. Med. Ctr. Adult CRS

    Durham, North Carolina, 27710

  • Greensboro CRS

    Greensboro, North Carolina, 27401

  • University of Southern California CRS

    Los Angeles, California, 90033

  • UCLA CARE Center CRS

    Los Angeles, California, 90035

  • Univ. of Miami AIDS CRS

    Miami, Florida, 33136

  • Vanderbilt Therapeutics CRS

    Nashville, Tennessee, 37204

  • Cornell CRS

    New York, New York, 10010

  • NY Univ. HIV/AIDS CRS

    New York, New York, 10016

  • HIV Prevention & Treatment CRS

    New York, New York, 10032

  • New Jersey Medical School- Adult Clinical Research Ctr. CRS

    Newark, New Jersey, 07103

  • Stanford CRS

    Palo Alto, California, 94304-5350

  • Hosp. of the Univ. of Pennsylvania CRS

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson Univ. Med. Ctr. CRS

    Philadelphia, Pennsylvania, 19107

  • Pitt CRS

    Pittsburgh, Pennsylvania, 15213-2582

  • The Research & Education Group-Portland CRS

    Portland, Oregon, 97210

  • The Miriam Hosp. ACTG CRS

    Providence, Rhode Island, 02906

  • Univ. of Rochester ACTG CRS

    Rochester, New York, 14642

  • Ucsd, Avrc Crs

    San Diego, California, 92103

  • Ucsf Aids Crs

    San Francisco, California, 94110

  • University of Washington AIDS CRS

    Seattle, Washington, 98104

  • Washington U CRS

    St Louis, Missouri, 63110

  • Bronx-Lebanon Hosp. Ctr. CRS

    The Bronx, New York, 10457

  • Harbor-UCLA Med. Ctr. CRS

    Torrance, California, 90502

  • Georgetown University CRS (GU CRS)

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: 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

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).

Read the detailed description

The varicella-zoster virus (VZV) which causes herpes zoster (HZ), or shingles, is associated with a painful skin rash and post-herpetic neuralgia (PHN). The incidence and severity of HZ and PHN increase as immune function decreases, as in elderly or HIV-infected people. The live VZV vaccine, ZOSTAVAX, has been shown to reduce the incidence and severity of HZ and PHN in people over the age of 60. The main purpose of this study is to determine whether a two-dose regimen of ZOSTAVAX is safe and well-tolerated in HIV-infected individuals with conserved immune function.

This study has two stages and two arms. It may last up to 24 weeks per subject. In Stage 1, 48 participants with CD4 cell counts of 200 or more cells/uL will be enrolled (24 participants with a CD4 count between 200 and 349 cells/uL and 24 participants with a CD4 count equaling 350 or more cells/uL). These participants will be randomized 3:1 to receive two doses of ZOSTAVAX or placebo at least six weeks apart. If certain safety criteria are met for Stage 1, enrollment will be opened to Stage 2. Stage 2 will enroll approximately 352 subjects with CD4+ T cell counts >= 200 cells/uL. In Stage 2, participants will be stratified using the same parameters as Stage 1 and will then be randomized 3:1 to receive either two doses of vaccine or placebo according to the same schedule. Participants will be followed for at least 42 days after each vaccination. Temperatures will be collected daily for 42 days following each vaccination. Telephone contact will also be made 2 to 3 days after each vaccination and at 24 weeks following the initial vaccination to obtain information regarding vaccination-related symptoms.

All participants will have between 6 and 8 study visits. At the screening visit, documentation of HIV status is required, and blood and urine collection, a physical exam, medical history, and clinical assessment will occur. At each visit, a targeted physical exam will occur. At some visits, blood and urine collection, and a clinical assessment will occur. Antiretroviral medications are not provided by this study.

Being tested
ZOSTAVAX, Placebo
Keywords
Herpes Zoster Vaccine, Herpes Zoster Virus, HIV
Medical subject headings
Herpes Zoster, HIV Infections, Chickenpox

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZOSTAVAXBiological

    Subcutaneous injection of 0.65 mL of ZOSTAVAX at Day 0 and Week 6

  • PlaceboBiological

    Subcutaneous injection of 0.65 mL of placebo at Day 0 and Week 6

Study groups in NCT00851786
Study groupRoleWhat they receive
1ExperimentalParticipants 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.
Receives: Biological: ZOSTAVAX
2Placebo 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
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: During the 6 week study period after receipt of any dose of ZOSTAVAX

Secondary outcomes (2)

  1. VZV Antibodies as Measured by gpELISA

    VZV antibody titer measured by gpELISA after one or two doses of ZOSTAVAX/placebo

    Measured: Within 6 weeks following one or two doses of ZOSTAVAX

  2. Geometric Mean Fold Rise (GMFR) in VZV ELISpot Responses

    VZV-specific cellular immune responses in peripheral blood mononuclear cells (PBMC) were tested by ELISpot assay in a subset of participants pooled across CD4 strata. GMFR is the geometric mean of the ratios of Week 6 or Week 12 post-vaccination antibody to the pre-vaccination antibody.

    Measured: Entry, Week 6, Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Feb 2009 (estimated)
  2. Study start29 Apr 2009
  3. Primary completion22 Sep 2011
  4. Study completion3 Jan 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
395 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00851786
Sponsor's protocol ID
A5247
Other IDs
10519, ACTG A5247
Status last verified
Jan 2018
First submitted
25 Feb 2009
Last updated
4 Nov 2021
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 16186734

  • Gilderman 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.

    PubMed 18077611

  • Holcomb K, Weinberg JM. A novel vaccine (Zostavax) to prevent herpes zoster and postherpetic neuralgia. J Drugs Dermatol. 2006 Oct;5(9):863-6.

    PubMed 17039651

  • Oxman 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.

    PubMed 15930418

  • Vafai 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.

    PubMed 11417752

  • Benson 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.

    PubMed 29590326

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ZOSTAVAX in people with Herpes Zoster and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 43 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 43 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Oct 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00851786, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2021.

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