HIV Infections
Conditions
Keywords
HIV, vaccine, lipopeptide, Tat, TUTI-16, THYMON
Brief summary
This protocol represents the second in human study of TUTI-16, and is being conducted to continue to gather safety and human immunogenicity (anti-HIV-1 Tat titers) data of subcutaneously administered TUTI-16.
Detailed description
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.
Interventions
BIOLOGICALTUTI-16 (0.2mg)
Two subcutaneous injections of 0.2 mg at Day 0, and Week 5.
BIOLOGICALTUTI-16 (1.0 mg)
Two subcutaneous injections of 1.0 mg at Day 0, and Week 5.
Sponsors
Thymon, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Males and Females * Age ≥18 and ≤50 years at Screening * HIV negative healthy subjects or HIV-1 seropositive subjects on effective ART for \>2 months (undetectable HIV plasma viremia), viral set point before ART \>3,000 * CD4+ T-cell count ≥ 500/mm3.
Exclusion criteria
* Pregnant/nursing females * Positive for HBV or HCV * Acute Herpetic event * Any clinically significant out-of range laboratory value * Routine or PRN consumption of immune suppressive medications that the 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti-Tat Antibody Titer | 5 weeks | ELISA based chemiluminescent assay to determine the anti-Tat antibody response |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TUTI-16 (0.2mg) Two subcutaneous injections of 0.2 mg at Day 0, and Week 5. | 10 |
| TUTI-16 (1.0 mg) Two subcutaneous injections of 1.0 mg at Day 0, and Week 5. | 5 |
| Total | 15 |
Baseline characteristics
| Characteristic | TUTI-16 (1.0 mg) | TUTI-16 (0.2mg) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 10 Participants | 15 Participants |
| Age Continuous | 36.4 years STANDARD_DEVIATION 4.56 | 38.4 years STANDARD_DEVIATION 8.51 | 38.4 years STANDARD_DEVIATION 7.64 |
| Region of Enrollment United States | 5 participants | 10 participants | 15 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 5 Participants | 10 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 10 | 1 / 5 |
| serious Total, serious adverse events | 0 / 10 | 0 / 5 |
Outcome results
Primary
Anti-Tat Antibody Titer
ELISA based chemiluminescent assay to determine the anti-Tat antibody response
Time frame: 5 weeks
Population: all participants enrolled were analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TUTI-16 (0.2mg) | Anti-Tat Antibody Titer | 401 ng/mL |
| TUTI-16 (1.0 mg) | Anti-Tat Antibody Titer | 887 ng/mL |