Live Zoster Vaccine in HIV-Infected Adults on Antiretroviral Therapy

NCT ID: NCT00851786

Last Updated: 2021-11-04

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

395 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-04-29

Study Completion Date

2012-01-03

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Herpes Zoster HIV Infections

Keywords

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Herpes Zoster Vaccine Herpes Zoster Virus HIV

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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1

Participants 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.

Group Type EXPERIMENTAL

ZOSTAVAX

Intervention Type BIOLOGICAL

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

2

Participants 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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

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

Interventions

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ZOSTAVAX

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

Intervention Type BIOLOGICAL

Placebo

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

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* Significant underlying illness preventing completion of the study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Adult AIDS Clinical Trials Group

NETWORK

Sponsor Role collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Constance A. Benson, MD

Role: STUDY_CHAIR

University of California, San Diego

Jeffrey L. Lennox, MD

Role: STUDY_CHAIR

Emory University

Locations

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Alabama Therapeutics CRS

Birmingham, Alabama, United States

Site Status

University of Southern California CRS

Los Angeles, California, United States

Site Status

UCLA CARE Center CRS

Los Angeles, California, United States

Site Status

Stanford CRS

Palo Alto, California, United States

Site Status

Ucsd, Avrc Crs

San Diego, California, United States

Site Status

Ucsf Aids Crs

San Francisco, California, United States

Site Status

Harbor-UCLA Med. Ctr. CRS

Torrance, California, United States

Site Status

University of Colorado Hospital CRS

Aurora, Colorado, United States

Site Status

Denver Public Health CRS

Denver, Colorado, United States

Site Status

Georgetown University CRS (GU CRS)

Washington D.C., District of Columbia, United States

Site Status

Univ. of Miami AIDS CRS

Miami, Florida, United States

Site Status

The Ponce de Leon Center CRS

Atlanta, Georgia, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, United States

Site Status

IHV Baltimore Treatment CRS

Baltimore, Maryland, United States

Site Status

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital ACTG CRS

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hosp. ACTG CRS

Boston, Massachusetts, United States

Site Status

Bmc Actg Crs

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, United States

Site Status

Henry Ford Hosp. CRS

Detroit, Michigan, United States

Site Status

Washington U CRS

St Louis, Missouri, United States

Site Status

Cooper Univ. Hosp. CRS

Camden, New Jersey, United States

Site Status

New Jersey Medical School- Adult Clinical Research Ctr. CRS

Newark, New Jersey, United States

Site Status

Cornell CRS

New York, New York, United States

Site Status

NY Univ. HIV/AIDS CRS

New York, New York, United States

Site Status

HIV Prevention & Treatment CRS

New York, New York, United States

Site Status

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Site Status

Bronx-Lebanon Hosp. Ctr. CRS

The Bronx, New York, United States

Site Status

Chapel Hill CRS

Chapel Hill, North Carolina, United States

Site Status

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, United States

Site Status

Greensboro CRS

Greensboro, North Carolina, United States

Site Status

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States

Site Status

Case CRS

Cleveland, Ohio, United States

Site Status

MetroHealth CRS

Cleveland, Ohio, United States

Site Status

The Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

The Research & Education Group-Portland CRS

Portland, Oregon, United States

Site Status

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson Univ. Med. Ctr. CRS

Philadelphia, Pennsylvania, United States

Site Status

Pitt CRS

Pittsburgh, Pennsylvania, United States

Site Status

The Miriam Hosp. ACTG CRS

Providence, Rhode Island, United States

Site Status

Vanderbilt Therapeutics CRS

Nashville, Tennessee, United States

Site Status

University of Washington AIDS CRS

Seattle, Washington, United States

Site Status

Countries

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Puerto Rico United States

References

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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.

Reference Type BACKGROUND
PMID: 16186734 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18077611 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 17039651 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15930418 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11417752 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29590326 (View on PubMed)

Other Identifiers

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10519

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5247

Identifier Type: -

Identifier Source: secondary_id

A5247

Identifier Type: -

Identifier Source: org_study_id