Study of Late Boost Strategies for HIV-uninfected Participants From Protocol RV 144

Study Overview
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Brief Summary
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The purpose of this study is to assess safety and tolerability of late boost regimens of AIDSVAX B/E alone, ALVAC-HIV alone, or ALVAC-HIV/AIDSVAX B/E combination in HIV-uninfected participants from RV 144.

Official Title
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Randomized, Double Blind Evaluation of Late Boost Strategies for HIV-uninfected Participants in the HIV Vaccine Efficacy Trial RV 144: Aventis Pasteur Live Recombinant ALVAC-HIV (vCP1521) Priming With VaxGen gp120 B/E (AIDSVAX B/E) Boosting in HIV-uninfected Thai Adults

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: ALVAC-HIV
* Biological: AIDSVAX B/E
* Biological: ALVAC-HIV Placebo
* Biological: AIDSVAX B/E Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have participated in RV144, received the active product, and completed all 4 vaccination visits per protocol. Must be able to understand and complete the informed consent process. Must successfully complete a Test of Understanding prior to enrollment The volunteer must answer 80% or 8 out of 10 of the questions correctly including two compulsory questions answered correctly. If the volunteer is unable to do so, he or she will be given two more opportunities to repeat the TOU. If after three attempts to pass the TOU the volunteer is still unable to do so, the volunteer will become ineligible for study participation. Must be in good general health without clinically significant medical history. HIV-uninfected per predefined algorithm within 45 days of enrollment. Laboratory screening analysis Hemoglobin: Women ≥12.0 g/dL. Men ≥12.5 g/dL White cell count: 4,000 to 11,000 cells/mm3 Platelets: 150,000 to 450,000/mm3 Normal liver function: ALT/AST ≤1.25 institutional upper limit of reference range Creatinine: ≤1.25 institutional upper limit of reference range Urinalysis (dipstick) for blood and protein no greater than 1+, glucose negative Female-Specific Criteria: Negative human choriogonadotropin (β-HCG) pregnancy test (urine) for women prior to each vaccination (same day). Be using adequate birth control methods for 45 days prior to the first vaccine/placebo vaccination and will continue to be followed for at least 3 months after the final vaccine/placebo vaccination. Adequate birth control is defined as follows: Contraceptive medications delivered orally, intramuscularly, vaginally, or implanted underneath the skin, surgical methods (hysterectomy or bilateral tubal ligation), condoms, diaphragms, intrauterine device (IUD), abstinence. Exclusion Criteria: 1. Women breast-feeding or pregnant (positive pregnancy test) or planning to become pregnant during the window between study enrollment and 3 months after the last vaccination visit. History of anaphylaxis or other serious adverse reaction to vaccines including to RV 144 vaccines, or allergies or reactions likely to be exacerbated by any component of the vaccine or placebo, including eggs, egg products, streptomycin, or neomycin. Subject has received any of the following substances: Chronic use of therapies which may modify immune response, such as IV immune globulin and systemic corticosteroids (in doses of > 20 mg/day prednisone equivalent for periods exceeding 10 days). The following exceptions are permitted and will not exclude study participation: use of corticosteroid nasal spray for rhinitis, topical corticosteroids for an acute uncomplicated dermatitis; or a short course (duration of 10 days or less, or a single injection) of corticosteroid for a nonchronic condition (based on investigator clinical judgment) at least 2 weeks prior to enrollment in this study. Blood products within 120 days prior to HIV screening. Immunoglobulins within 14 days prior to HIV screening. Any vaccine within 14 days prior to initial study vaccine administration in the present study. Receipt of investigational HIV vaccine product other than the RV 144 regimen. Investigational research agents within 30 days prior to initial study vaccine administration in the present study. Use of anti-tuberculosis prophylaxis or therapy during the past 90 days. Any medical, psychiatric, social condition, occupational reason, or other responsibility that, in the judgment of the investigator, is a contraindication to protocol compliance or impairs a subject's ability to give informed consent. Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder; disorder requiring lithium; or within 5 years prior to enrollment, a history of suicide plan or attempt. Study site employees who are involved in the protocol and/or may have direct access to study related area.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I<br>ALVAC-HIV + AIDSVAX B/E or ALVAC-HIV placebo + AIDSVAX B/E placebo at Weeks 0 and 24 | Biological: ALVAC-HIV<br>* 1 mL per injection containing 10^6 CCID50/dose administered<br>* Other names: (vCP1521);Biological: AIDSVAX B/E<br>* 1 mL per injection (300 ug dose/antigen for a total of 600ug/dose administered)<br>Biological: ALVAC-HIV Placebo<br>* 1 ml per injection<br>Biological: AIDSVAX B/E Placebo<br>* 1 ml per injection<br>|
| Experimental: Group II<br>AIDSVAX B/E or AIDSVAX B/E placebo at Weeks 0 and 24 | Biological: AIDSVAX B/E<br>* 1 mL per injection (300 ug dose/antigen for a total of 600ug/dose administered)<br>Biological: AIDSVAX B/E Placebo<br>* 1 ml per injection<br>|
| Experimental: Group III<br>ALVAC-HIV or ALVAC-HIV placebo at Weeks 0 and 24 | Biological: ALVAC-HIV<br>* 1 mL per injection containing 10^6 CCID50/dose administered<br>* Other names: (vCP1521);Biological: ALVAC-HIV Placebo<br>* 1 ml per injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Immunogenicity Endpoint | Characterization of vaccine-induced immune responses by IFN-gamma ELISPOT, intracellular cytokine staining (ICS), and 3H-thymidine incorporation assay. | Week 0 | 
| Safety Endpoints | Post-vaccination reactions including erythema, induration, pain/tenderness, swelling, limitation of arm movement, fever, tiredness, chills, myalgia, arthralgia, headache, nausea, dizziness, and rash will be assessed and recorded on diary cards. | During the 3 days post-vaccination | 
| Primary Immunogenicity Endpoint | Characterization of vaccine-induced immune responses by IFN-gamma ELISPOT, intracellular cytokine staining (ICS), and 3H-thymidine incorporation assay. | Week 2 | 
| Primary Immunogenicity Endpoint | Characterization of vaccine-induced immune responses by IFN-gamma ELISPOT, intracellular cytokine staining (ICS), and 3H-thymidine incorporation assay. | Week 24 | 
| Primary Immunogenicity Endpoint | Characterization of vaccine-induced immune responses by IFN-gamma ELISPOT, intracellular cytokine staining (ICS), and 3H-thymidine incorporation assay. | Week 26 | 
| Primary Immunogenicity Endpoint | Characterization of vaccine-induced immune responses by IFN-gamma ELISPOT, intracellular cytokine staining (ICS), and 3H-thymidine incorporation assay. | Week 48 | 
| Primary Immunogenicity Endpoint | Characterization of vaccine-induced immune responses by IFN-gamma ELISPOT, intracellular cytokine staining (ICS), and 3H-thymidine incorporation assay. | Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Immunogenicity Endpoints | Characterization of vaccine-induced immune responses by lymphoproliferation assays (LPA), human leukocyte antigen (HLA) subtyping, characterization of natural killer (NK) cells using multiparameter flow, assessment of APOBEC 3G (A3G) antiretroviral factor expression, B-cell ELISPOT, HIV-specific binding antibody assays, neutralizing antibody assays, mucosal IgG and IgA binding antibody assays, antibody-dependent cell mediated cytotoxicity (ADCC) and antibody-dependent cell mediated viral inhibition (ADCVI) assays | Baseline, Weeks 2, 24, 26, 48 and 72 |