Clinical Study of TUTI-16 in Asymptomatic HIV-1 Infected Subjects

Study Overview
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Brief Summary
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This protocol represents the first in human study of TUTI-16, and is being conducted to establish the safety and human immunogenicity (anti-HIV-1 Tat titers) of subcutaneously administered TUTI-16. Activity of TUTI-16 will also be determined in minimizing HIV-1 viral loads and sustaining CD4+ T-cell levels.

Detailed Description
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HIV-1 Tat protein, a virally encoded toxin, is secreted by HIV-1 infected cells and acts on uninfected cells, rendering them permissive for HIV-1 replication. HIV-1 Tat enhances chronic viral replication and induces immune suppression. Antibodies to Tat inhibit this Tat-mediated transcellular activation in vitro and minimize chronic plasma viremia. HIV-1 Tat activities can be blocked in vitro and in vivo by anti-Tat antibodies. The Thymon Universal Tat Immunogen (TUTI-16) is a fully synthetic, self-adjuvanting lipopeptide vaccine that is water soluble and administered by subcutaneous injection. In preclinical studies, a priming dose and a three week boost in rats induced a high titer antibody response to the eight known distinct epitope variants of HIV-1 Tat protein. These antibodies block the function of the HIV-1 Tat protein (toxin), which is essential to the maintenance of chronic HIV-1 viremia. Therefore, TUTI-16 has potential as a therapeutic vaccine for HIV-1 in humans.

Official Title
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Phase I/IIA Clinical Study of TUTI-16 in Asymptomatic HIV-1 Infected Subjects

Conditions
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HIV Infections

Intervention / Treatment
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* Other: Placebo
* Biological: TUTI-16 (0.03mg)
* Biological: TUTI-16 (0.1mg)
* Biological: TUTI-16 (0.6mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and Females Age ≥18 and ≤50 years at Screening HIV-1 seropositive asymptomatic and in generally good health no prior anti-retroviral therapy within 6 months of screening viral load ≥ 3,000 ≤ 100,000 HIV-1 RNA copies/mL CD4+ T-cell count ≥ 400/mm3. Exclusion Criteria: Pregnant/nursing females positive for HBV or HCV acute Herpetic event any clinically significant out-of range laboratory value subject is unable or unwilling to discontinue during the study participation in another investigational drug/vaccine study within 30 days preceding the first injection of investigational agent in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Subcutaneous injection on Day 0, Day 28, and Day 84<br>|
| Experimental: TUTI-16 0.03 mg<br>Subcutaneous injection on Day 0, Day 28, and Day 84 | Biological: TUTI-16 (0.03mg)<br>* Subcutaneous injection on Day 0, Day 28, and Day 84<br>|
| Experimental: TUTI-16 0.1 mg<br>Subcutaneous injection on Day 0, Day 28, and Day 84 | Biological: TUTI-16 (0.1mg)<br>* Subcutaneous injection on Day 0, Day 28, and Day 84<br>|
| Experimental: TUTI-16 0.6 mg<br>Subcutaneous injection on Day 0, Day 28, and Day 84 | Biological: TUTI-16 (0.6mg)<br>* Subcutaneous injection on Day 0, Day 28, and Day 84<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV Viral Load | Change in HIV viral load from baseline | baseline and 20 weeks | 
| CD4+ T-cell Count | Change in CD4+ T-cell count from baseline | baseline and 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of Anti-Tat Antibodies | Determination of change in anti-Tat antibody level | baseline and 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, vaccine, lipopeptide, Tat, TUTI-16, THYMON, Treatment Naive