Ignite Creation Date:
2024-05-06 @ 12:11 AM
Last Modification Date:
2024-10-26 @ 10:46 AM
Study NCT ID:
NCT01513135
Status:
COMPLETED
Last Update Posted:
2016-03-04
First Post:
2012-01-17
Brief Title:
A Phase Il of a Therapeutic Recombinant Biologically Active HIV-1 Tat Protein Vaccine in HIV-Infected Anti-Tat Negative ARV-Treated Adult Volunteers
Sponsor:
Barbara Ensoli MD
Organization:
Istituto Superiore di Sanità
Study Overview
Official Title:
A Phase Il Randomized Double-Blind Placebo-Controlled Trial to Evaluate the Immunogenicity and Safety of a Therapeutic Recombinant Biologically Active HIV-1 Tat Protein Vaccine in HIV-Infected Anti-Tat Negative ARV-Treated Adult Volunteers
Status:
COMPLETED
Status Verified Date:
2016-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ISS T-003
Brief Summary:
Tat is a key HIV regulatory protein produced very early after infection prior to virus integration and necessary for viral gene expression cell-to-cell virus transmission and disease progression Previous studies in natural HIV infection indicated that the presence of a Tat-specific immune response correlates with a lower incidence and reduced risk of progression to AIDS as compared to anti-Tat negative individuals suggesting that an immune response to Tat may exert a protective role and control the progression to AIDS in vivo Moreover Tat is conserved in its immunogenic regions both B and T cell among all subtypes subtypes Recent data in fact indicate an effective cross-clade recognition of clade B strain-derived BH-10 Tat protein from the HTLV-IIIB lab-adapted virus strain Buttò 2003 which was isolated about 30 years ago Ratner 1985 by sera from individuals infected with viruses circulating at the present in Italy and in Africa thus reflecting the high degree of conservation of the corresponding Tat regions and providing strong formal evidence that a Tat-based vaccine may indeed be used in the different geographic areas of the world since it is capable of inducing a broad immune response against different virus clades Based on this rationale and on the positive results of preclinical Cafaro Nat Med 1999 and phase I preventive and therapeutic clinical trials with Tat protein ISS P-001 and ISS T-001 respectively Ensoli AIDS 2008 Vaccine 2009 Longo Vaccine 2009 Bellino RRCT 2009 a phase II therapeutic open label clinical study with Tat protein ISS T-002 ClinicalTrialsgov NCT00751595 was sponsored by ISS and activated in 11 clinical sites in Italy in HIV-infected HAART-treated subjects Ensoli F Retrovirology 2015In this study subjects are randomized into two arms to receive 3 or 5 vaccinations monthly each arm is composed of two treatment groups receiving 7 5 or 30 µg of Tat respectivelyResults obtained in 168 individuals after trial completion 48 weeks as well as after a follow-up of 144 weeks for a subgroup of vaccines indicated that Tat vaccination is safe immunogenic and capable of reducing the immune dysregulation which persists despite HAART in treated individuals Ensoli et alPLoS ONE 2010 Anti-Tat Abs were induced in most patients 79 with the highest frequency and durability in the Tat 30 µg groups 89 particularly when given 3 times 92 Ensoli BPLoS ONE 2010 Ensoli F Retrovirology 2015 Moreover vaccination promoted a durable and significant restoration of T B natural killer NK cells and CD4 and CD8 central memory subsets Moreover a significant reduction of blood proviral DNA was seen after week 72 particularly under PI-based regimens and with Tat 30 µg given 3 times 30 μg 3x reaching a predicted 70 decay after 3 years from vaccination with a half-life of 88 weeks This decay was significantly associated with anti-Tat IgM and IgG Abs and neutralization of Tat-mediated entry of oligomeric Env in dendritic cells which predicted HIV-1 DNA decay Finally the 30 μg 3x group was the only one showing significant increases of NK cells and CD38HLA-DRCD8 T cells a phenotype associated with increased killing activity in elite controllers Ensoli F Retrovirology 2015 These data indicate that Tat immunization represents a promising pathogenesis-driven intervention to intensify HAART efficacy Ensoli et alPLoS ONE 2010
Detailed Description:
Based on this the ISS T-003 study in South Africa was started the study was a phase II randomized double-blinded placebo controlled clinical trial to evaluate the immunogenicity as a primary end-point and the safety as a secondary end-point of a therapeutic recombinant biologically active HIV-1 Tat vaccine in HIV-1 infected anti-Tat antibody negative ARV-treated adult volunteers with chronically suppressed HIV-1 infection as indicated by a HIV-1 plasma viraemia 400 copiesml and a CD4 T cell count 200 cellsμl at screening and documented at least once during the 12 month period prior to screening irrespective of the pre-ARV CD4 nadir
After a screening period of up to 21 days the study duration will be 48 weeks including an 8 week treatment phase during which 3 vaccinations will be administered at 4-week intervals and a 40 week follow-up phase
This study will be conducted at 1 clinical site in South Africa 200 Subjects were randomized in a 11 ratio to one of the two treatment groups Tat 30 mcg or placebo administered intradermally 3 times
After a screening period of up to 21 days the study duration will be 48 weeks including an 8 week treatment phase during which 3 vaccinations will be administered at 4-week intervals and a 40 week follow-up phase
This study will be conducted at 1 clinical site in South Africa 200 Subjects were randomized in a 11 ratio to one of the two treatment groups Tat 30 mcg or placebo administered intradermally 3 times
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None