HIV Infections
Conditions
Keywords
HIV, vaccine, lipopeptide, Tat, TUTI-16, THYMON, Treatment Naive
Brief summary
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
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
OTHERPlacebo
Subcutaneous injection on Day 0, Day 28, and Day 84
BIOLOGICALTUTI-16 (0.03mg)
Subcutaneous injection on Day 0, Day 28, and Day 84
BIOLOGICALTUTI-16 (0.1mg)
Subcutaneous injection on Day 0, Day 28, and Day 84
BIOLOGICALTUTI-16 (0.6mg)
Subcutaneous injection on Day 0, Day 28, and Day 84
Sponsors
Thymon, LLC
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HIV Viral Load | baseline and 20 weeks | Change in HIV viral load from baseline |
| CD4+ T-cell Count | baseline and 20 weeks | Change in CD4+ T-cell count from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determination of Anti-Tat Antibodies | baseline and 16 weeks | Determination of change in anti-Tat antibody level |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (0.03mg TUTI-16) Subcutaneous injection over the deltoid muscle in the upper arm on Day 0, Day 28, and Day 84 | 6 |
| Group 2 (0.1mg TUTI-16) Subcutaneous injection over the deltoid muscle in the upper arm on Day 0, Day 28, and Day 84 | 7 |
| Group 3 (0.6mg TUTI-16) Subcutaneous injection over the deltoid muscle in the upper arm on Day 0, Day 28, and Day 84 | 6 |
| Placebo Subcutaneous injection over the deltoid muscle in the upper arm on Day 0, Day 28, and Day 84 | 5 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Group 2 (0.1mg TUTI-16) | Group 3 (0.6mg TUTI-16) | Group 1 (0.03mg TUTI-16) | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 6 Participants | 6 Participants | 5 Participants | 24 Participants |
| Age Continuous | 48 years STANDARD_DEVIATION 9 | 41 years STANDARD_DEVIATION 8 | 44 years STANDARD_DEVIATION 10 | 51 years STANDARD_DEVIATION 5 | 45.9 years STANDARD_DEVIATION 8.67 |
| Region of Enrollment United States | 7 participants | 6 participants | 6 participants | 5 participants | 24 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 6 Participants | 5 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 6 | 5 / 7 | 5 / 6 | 4 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 5 |
Outcome results
Primary
CD4+ T-cell Count
Change in CD4+ T-cell count from baseline
Time frame: baseline and 20 weeks
| Arm | Measure | Value (LOG_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 (0.03mg TUTI-16) | CD4+ T-cell Count | -65 cells/mm3 | Standard Error 48 |
| Group 2 (0.1mg TUTI-16) | CD4+ T-cell Count | -116 cells/mm3 | Standard Error 56 |
| Group 3 (0.6mg TUTI-16) | CD4+ T-cell Count | 14 cells/mm3 | Standard Error 53 |
| Placebo | CD4+ T-cell Count | -59 cells/mm3 | Standard Error 22 |
p-value: 0.045ANOVA
Primary
HIV Viral Load
Change in HIV viral load from baseline
Time frame: baseline and 20 weeks
| Arm | Measure | Value (LOG_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 (0.03mg TUTI-16) | HIV Viral Load | -0.18 HIV RNA copies/mL | Standard Error 0.12 |
| Group 2 (0.1mg TUTI-16) | HIV Viral Load | -0.05 HIV RNA copies/mL | Standard Error 0.13 |
| Group 3 (0.6mg TUTI-16) | HIV Viral Load | 0.002 HIV RNA copies/mL | Standard Error 0.11 |
| Placebo | HIV Viral Load | 0.26 HIV RNA copies/mL | Standard Error 0.56 |
p-value: 0.008ANOVA
Secondary
Determination of Anti-Tat Antibodies
Determination of change in anti-Tat antibody level
Time frame: baseline and 16 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 (0.03mg TUTI-16) | Determination of Anti-Tat Antibodies | 20 ng/mL |
| Group 2 (0.1mg TUTI-16) | Determination of Anti-Tat Antibodies | 84 ng/mL |
| Group 3 (0.6mg TUTI-16) | Determination of Anti-Tat Antibodies | 84 ng/mL |
| Placebo | Determination of Anti-Tat Antibodies | 20 ng/mL |