Live Zoster Vaccine in HIV-Infected Adults on Antiretroviral Therapy - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators:	Adult AIDS Clinical Trials Group Merck
Information provided by (Responsible Party):	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00851786

Purpose

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 test the safety and tolerability of ZOSTAVAX in HIV-infected adults.

Condition	Intervention	Phase
Herpes Zoster HIV Infections	Biological: Zoster Vaccine Live Biological: Placebo	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Prevention
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

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS Shingles

Drug Information available for: Zostavax

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Toleration of a two dose regimen of ZOSTAVAX measured by occurrence of serious adverse events (AEs) or Division of AIDS (DAIDS) Grade 3 and 4 Signs and Symptoms, excluding serious AEs related to trauma [ Time Frame: During the 6 week study period after receipt of any dose of ZOSTAVAX ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Varicella-zoster virus (VZV) antibody response as determined by gpELISA in HIV-infected adults virologically suppressed on potent combination ART with conserved immune function [ Time Frame: Within 6 weeks following one or two doses of ZOSTAVAX ] [ Designated as safety issue: Yes ]
To assess VZV-specific cellular immune responses in Stage 2 by intracellular cytokine staining, Interferon-gamma ELISPOT, or other appropriate cellular immunological assays in a subset of the first 40 subjects in Arm 1 or 2 [ Time Frame: At the opening of Stage 2 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	400
Study Start Date:	June 2009
Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Participants with CD4 cell counts of 350 cells/mm3 or greater in Stage 1 and 2 will be given one dose of ZOSTAVAX at Day 0 and Week 6 and will be followed for 42 days following each vaccination	Biological: Zoster Vaccine Live Subcutaneous injection of 0.65 mL of ZOSTAVAX at Day 0 and Week 6
Experimental: 2 Participants with CD4 cell counts from 200-349 cells/mm3 in Stage 1 and 2 will be given one dose of ZOSTAVAX at Day 0 and Week 6 and will be followed for 42 days following each vaccination	Biological: Zoster Vaccine Live Subcutaneous injection of 0.65 mL of ZOSTAVAX at Day 0 and Week 6
Placebo Comparator: 3 Participants with CD4 cell counts of 350 cells/mm3 or greater in Stage 1 and 2 will be given one dose of placebo at Day 0 and Week 6 and will be followed for 42 days following each placebo vaccination	Biological: Placebo Subcutaneous injection of 0.65 mL of placebo at Day 0 and Week 6
Placebo Comparator: 4 Participants with CD4 cell counts from 200-349 cells/mm3 or greater in Stage 1 and 2 will be given one dose of placebo at Day 0 and Week 6 and will be followed for 42 days following each placebo vaccination	Biological: Placebo Subcutaneous injection of 0.65 mL of placebo at Day 0 and Week 6

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 three arms. It may last up to 24 weeks per subject. In Stage 1, 48 participants with CD4 cell counts of 200 or more cells/microliter will be enrolled (24 participants with a CD4 count between 200 and 349 cells/microliter and 24 participants with a CD4 count equaling 350 or more cells/microliter). These participants will be randomized 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. In Stage 2, participants will be stratified using the same parameters as Stage 1 and will then be randomized to receive either two doses of vaccine or placebo. 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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/microliter 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

Exclusion Criteria:

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
Any illness that might interfere with the interpretation of the study or prevent completion of the study
Use of immunosuppressive therapy. More information can be found in the protocol.
Any suppressive antiviral therapy with activity against herpes viruses within 7 days prior to study entry or during 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 or breast feeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00851786

Show 47 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Adult AIDS Clinical Trials Group

Merck

Investigators

Study Chair:	Constance A. Benson, MD	Emory University
Study Chair:	Jeffrey L. Lennox, MD	Emory University

More Information

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.

Gilderman LI, Lawless JF, Nolen TM, Sterling T, Rutledge RZ, Fernsler DA, Azrolan N, Sutradhar SC, Wang WW, Chan IS, Schlienger K, Schödel 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. Epub 2007 Dec 12.

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

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.

Vafai A, Berger M. Zoster in patients infected with HIV: a review. Am J Med Sci. 2001 Jun;321(6):372-80. Review.

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00851786 History of Changes
Other Study ID Numbers:	ACTG A5247, 10519
Study First Received:	February 25, 2009
Last Updated:	January 17, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Herpes Zoster Vaccine
Herpes Zoster Virus
HIV

Additional relevant MeSH terms:

Acquired Immunodeficiency Syndrome
HIV Infections
Herpes Zoster
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases

Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Herpesviridae Infections
DNA Virus Infections

ClinicalTrials.gov processed this record on February 09, 2012