ACTG 5247: Phase 2 trial to evaluatre the safety, tolerability, and Immunogenicity of ZOSTAVAX in HIV-1 infected Adults
Contact Information
Stanford University School of Medicine 300 Pasteur Drive Stanford, CA 94305Brief
The main purpose of this study is to test a research vaccine called ZOSTAVAX®, a vaccine that helps to stimulate the immune system (part of your body that is designed to protect you against foreign materials that enter from outside your body) to help fight complications of infection with a virus called herpes zoster, the virus that causes zoster or shingles. Herpes zoster or shingles is a virus infection that causes a painful skin rash, usually in older people or people with suppressed immune systems like people with HIV infection. This study will test ZOSTAVAX® to see if it is safe and tolerable in HIV-infected people. The study will also test the ZOSTAVAX® vaccine to see if it has an effect on your immune system’s ability to develop responses against the virus that causes herpes zoster or shingles.
Recruiting Status:
RecruitingStanford Recruiting Status:
RecruitingCondition(s):
Intervention(s):
- Vaccine: ZASTAVAX (Zoster Vaccine Live)
Phase:
Phase 2Eligibility
Ages Eligible for Study:
18 years to Any AgeGenders Eligible for Study:
Male and FemaleHealth of Volunteers:
People with the conditions listed in this trial can participate as controls.Key Inclusion Criteria:
1 HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
2 HIV-1-infected adults who have been on a stable (no change in ART regimen within 90 days prior to entry) potent combination ART regimen and have had an undetectable plasma HIV-1 RNA level (defined as <50 copies/mL by UltraSensitive Roche Amplicor HIV-1 Monitor Test, version 1.5, <48 copies/mL by Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, or <75 copies/mL by Versant HIV-1 RNA 3.0 (bDNA) assay at any laboratory that has a Clinical Laboratory Improvement Amendments [CLIA] certification or its equivalent) documented at 90-180 days prior to study entry, have an undetectable plasma HIV RNA level within 30 days of study entry, and no known detectable HIV-1 RNA level between the documented pre-entry level and study entry.
NOTE: Potent combination ART regimen is defined as a combination of at least two antiretroviral drugs from at least two drug classes or at least three antiretroviral drugs from a single drug class, e.g., a protease inhibitor (PI) + non-nucleoside analogue reverse transcriptase inhibitor (NNRTI); PI + 2 NRTIs; NNRTI + 2 NRTIs; 3 NRTIs; NNRTI + integrase, etc.; PIs boosted with ritonavir are considered a single drug for the purposes of this definition.
3 CD4+ T cell count ≥350 cells/µL for Stage I enrollment or ≥200 cells/µL for Stage II enrollment obtained within 30 days prior to study entry at any laboratory that has a CLIA certification or its equivalent.
4 Laboratory values obtained within 90 days prior to study entry.
• Hemoglobin 7.0 g/dL
• Platelet count 50,000/mm3
• Creatinine 3  ULN
• AST (SGOT), ALT (SGPT), and alkaline phosphatase 5  ULN
5 For females of reproductive potential (women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy, or bilateral oophorectomy and/or tubal ligation), will need a negative serum or urine pregnancy test within 24 hours prior to study entry.
NOTE: Acceptable documentation of hysterectomy and bilateral oophorectomy, tubal ligation, tubal micro-inserts, vasectomy, and menopause in subject-reported history.
6 All subjects must agree not to participate in the conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the subject/partner must use at least two reliable methods of contraception, (condoms, with or without a spermicidal agent; a diaphragm or cervical cap with spermicide; an intrauterine device (IUD); contraceptive sponge; vasectomy or hormone-based contraceptive), during the 12-week duration of the study.
7 History of varicella or herpes zoster more than 1 year prior to vaccination or VZV seropositivity at any time prior to entry.
8 Men and women age 18 years.
9 Ability and willingness of subject or legal guardian/representative to provide informed consent.
Key Exclusion Criteria:
1 History of nadir CD4+ count <100 cells/µL.
2 Known or suspected immune dysfunction that is caused by a medical condition or any cause other than HIV infection.
Examples of medical conditions associated with immune dysfunction include 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.
3 Pregnancy (including subjects who are expecting to conceive within 3 months of the second vaccination) or breast-feeding.
4 Prior receipt of any varicella or zoster vaccine.
5 History of allergy/sensitivity or any hypersensitivity to any vaccine component, including gelatin or neomycin.
6 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 12-week study period.
7 Administration of any live virus vaccine within 28 days prior to study entry or any inactivated vaccine within 7 days prior to study entry.
NOTE: In studies of ZOSTAVAX®, and other vaccine studies, live virus vaccines are prohibited during the 4 weeks prior to vaccination. Live vaccines administered less than 4 weeks prior to vaccination or expected during the 12 weeks should be excluded to prevent potential interference with immunogenicity responses and confounding safety results (see section 5.1.4 for details).
8 Scheduled administration of any live virus vaccine or inactivated vaccine during the period on study.
NOTE: In studies of ZOSTAVAX®, and other vaccine studies, live virus vaccines are prohibited during the 4 weeks prior to vaccination. Live vaccines administered less than 4 weeks prior to vaccination or expected during the 12 weeks should be excluded to prevent potential interference with immunogenicity responses and confounding safety results (see section 5.1.4 for details).
9 Participation in an investigational drug study within the last 30 days prior to study entry.
10 Any acute intercurrent illness that might interfere with the interpretation of the study.
11 Significant underlying illness preventing completion of the study.
12 Use of immunosuppressive therapy.
NOTE: Subjects on corticosteroids should be excluded if they are receiving or are expected to receive, in the period from 4 weeks prior to study entry until 6 weeks post vaccination dose 2, systemic doses greater than required for physiological replacement, i.e., >10 mg of prednisone (or equivalent) and for >2 weeks. Excluded immunosuppressive therapies also include chemotherapeutic agents used to treat cancer or other conditions, and treatments associated with organ or bone marrow transplantation.
13 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 of study entry, or expected use through the 12-week study period except where necessary for acute treatment of intercurrent viral infection.
14 Any episode of VZV reactivation in the 12 months immediately prior to study entry.
15 Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
16 Any other reason that, in the opinion of the investigator, might interfere with the evaluation required by the study.
Additional Study Details
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 FunctionAnticipated start date:
4/1/2008Lead Sponsor:
AIDS Clinical Trials NetworkInvestigator(s):
- Andrew R Zolopa
- Michael J. Harbour
Study Type:
InterventionalPurpose:
TreatmentAllocation:
RandomizedMasking:
Double BlindControl:
noneAssignment:
ParallelEndpoints:
Safety/EfficacyPrimary Outcomes:
- To determine whether a 2-dose regimen of ZOSTAVAX® is well tolerated when administered to HIV-1-infected adults virologically suppressed on potent combination ART with conserved immune function, where tolerability is measured by a composite safety endpoint of the occurrence of serious adverse events (AEs) or the Division of AIDS (DAIDS) Grade 3 and 4 Signs and Symptoms, excluding serious AEs related to trauma, during the 6-week study period after receipt of any dose of ZOSTAVAX®.
Secondary Outcomes:
- To assess the VZV antibody response (by gpELISA) 6 weeks after 1 or two doses of ZOSTAVAX® in HIV-1-infected adults virologically suppressed on potent combination ART with conserved immune function.
- To assess VZV-specific cellular immune responses (by intracellular cytokine staining, Interferon-gamma (IFNã) ELISPOT or other appropriate cellular immunological assays) in a subset of the first 40 subjects entering each CD4 stratum at the opening of Stage II.
Total Number to be Enrolled:
400Total Number to be Enrolled at Stanford:
5More Information
Secondary ID(s):
- A5247
Locations & Contacts
Stanford Locations & Contacts:
Stanford University School of Medicine 300 Pasteur Drive Stanford, CA 94305Non-Stanford Locations:
The Stanford website does not have any locations outside of Stanford listed for this trial. You may want to check clinicaltrials.gov for posible additional locations.
This listing was last updated:
4/27/2009PLEASE NOTE:
Study Coordinators and Research Nurses cannot give medical advice over the phone. Telephone numbers are provided for obtaining additional information on specific clinical research trials only. If you have specific questions which require clinical expertise, please call your primary care physician. If you do not have a primary care physician please feel free to call the SHC Physician Referral Service at (800) 756-9000 or send an email.
Help
Administrator Login