HIV-1 Infection Clinical Trial
Official title:
A Pilot Study of Safety and Feasibility of T-Cell Immunotherapy Using Lentivirus Vector-Expressed RNAi in Autologous T-Cells of HIV-1 Infected Patients Who Have Failed Anti-Retroviral Therapy
This is a pilot study to determine the safety and feasibility of lentivirus-transduced T-cell immunotherapy in patients who have failed highly active anti-retrovirus therapy (HAART).
Study Design This is a pilot study to determine the safety and feasibility of
lentivirus-transduced T cell immunotherapy in patients who have failed highly active
anti-retrovirus therapy (HAART) as defined by HIV levels or by intolerance to drug therapy.
The lentivirus vector induces 3 forms of anti-HIV RNA: RNAi in the form of a short hairpin
RNA (shRNA) targeted to an exon in HIV-1 tat/rev (shI), a decoy for HIV TAT-activated RNA
(TAR), and a ribozyme that targets the host T cell CCR5 cytokine receptor (CCR5RZ). The
vector is called rHIV7-shI-TAR-CCR5RZ and will be used in the transduction and expansion of
autologous CD4-enriched T cells. Doses of 1 x 109 T cells will be given at 0, +6, and +12
weeks to the first cohort of 3 subjects. Following completion of this cohort, if no serious
adverse events have occurred within 3 weeks of the last infusion, then the next cohort will
receive 10 x 109 T cells at 0, +6, and +12 weeks using the same 8 week spacing between
subjects.
Study Endpoints:
The primary endpoints of this pilot study are patient safety and study feasibility. Safety
will be determined by clinical and laboratory observation and grading of adverse events,
analysis of T cell repertoire clonality, and evaluation of HIV isolates for evidence of
vector recombination. Feasibility will be determined by the ability to obtain suitable
numbers of expanded T cells and expression of the RNA transgenes in these cells. The
secondary endpoints are the duration of T cell circulation in blood post-infusion and the
effect of the T cell infusion on CD4 count and on HIV load. Conventional CD4 counts and HIV
RNA levels in blood will be determined at follow-up intervals.
Subject Eligibility and Number. Subjects must be HIV-1 infected adults ≥18 and ≤60 years of
age who have been on HAART therapy for at least one year and have evidence of virologic
failure defined by >5000 HIV RNA genome copies (gc) per mL in blood. Subjects must have a
CD4 count of at least 200 CD4+ T cells/mL. This pilot study is expected to accrue five
evaluable patients.
;
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT03188523 -
Activity of MK-8504 in Anti-retroviral-naïve, Human Immunodeficiency Virus 1 (HIV-1) Infected Participants (MK-8504-002)
|
Phase 1 | |
Active, not recruiting |
NCT06185452 -
Implementation of Out-of-HOspital Administration of the Long-Acting Cabotegravir+Rilpivirine
|
Phase 4 | |
Recruiting |
NCT02881320 -
Study of Bictegravir/Emtricitabine/Tenofovir Alafenamide Fixed Dose Combination in Adolescents and Children With Human Immunodeficiency Virus-1
|
Phase 2/Phase 3 | |
Completed |
NCT02542852 -
A Study of a Nucleoside Sparing Regimen in HIV-1 Infected Patients With Detectable Viremia
|
Phase 2 | |
Completed |
NCT02513771 -
Sitagliptin for Reducing Inflammation and Immune Activation
|
Phase 2 | |
Terminated |
NCT02732457 -
Allogeneic Hematopoietic Stem Cell Transplantation in HIV-1 Infected Patients
|
||
Completed |
NCT02057796 -
Systematic Empirical vs. Test-guided Anti-TB Treatment Impact in Severely Immunosuppressed HIV-infected Adults Initiating ART With CD4 Cell Counts <100/mm3
|
Phase 4 | |
Completed |
NCT01989910 -
Compare the Efficacy and Safety of Raltegravir Versus Efavirenz Combination Therapy in Treatment-naïve HIV-1 Patients
|
Phase 4 | |
Completed |
NCT01627678 -
Immunotherapy With Vacc-C5 With Adjuvant GM-CSF or Alhydrogel in HIV-1-infected Subjects on ART
|
Phase 1/Phase 2 | |
Completed |
NCT01704781 -
Vacc-4x + Lenalidomide vs. Vacc-4x +Placebo in HIV-1-infected Subjects on Antiretroviral Therapy (ART)
|
Phase 1/Phase 2 | |
Completed |
NCT01403051 -
High Dose Vitamin D and Calcium for Bone Health in Individuals Initiating HAART
|
Phase 2 | |
Completed |
NCT01348308 -
Immuno-stimulation With Maraviroc Combined to Antiretroviral Therapy in Advanced Late Diagnosed HIV-1 Infected Patients
|
Phase 3 | |
Completed |
NCT01466595 -
Rifaximin as a Modulator of Microbial Translocation and Immune Activation
|
Phase 2 | |
Completed |
NCT01019551 -
Therapeutic Intensification Plus Immunomodulation in HIV-infected Patients
|
Phase 2 | |
Completed |
NCT01511809 -
Efficacy of Atazanavir/Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression
|
Phase 3 | |
Terminated |
NCT01130376 -
Novel Interventions in HIV-1 Infection
|
Phase 1 | |
Completed |
NCT00323687 -
SONETT: Switch Study to Once Daily HIV Treatment Regimen With Truvada
|
Phase 4 | |
Completed |
NCT04003103 -
Safety and Pharmacokinetics of Oral Islatravir (MK-8591) Once Monthly in Participants at Low Risk of Human Immunodeficiency Virus 1 (HIV-1) Infection (MK-8591-016)
|
Phase 2 | |
Completed |
NCT02527096 -
A Trial Evaluating Maintenance Therapy With Lamivudine (Epivir®) and Dolutegravir (Tivicay®) in Human Immunodeficiency Virus 1 (HIV-1) Infected Patients Virologically Suppressed With Triple Highly Active Antiretroviral Therapy (HAART) (ANRS 167 Lamidol)
|
Phase 2 | |
Active, not recruiting |
NCT04776252 -
Open-label, Follow-up of Doravirine/Islatravir (DOR/ISL 100 mg/0.75mg) for Participants With Human Immunodeficiency Virus-1 (HIV-1) Infection (MK-8591A-033)
|
Phase 3 |