Phase 1 Dose Escalation Study of Autologous T-cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases in HIV-Infected Patients
HIV Infection, HIV Infections
About this trial
This is an interventional treatment trial for HIV Infection focused on measuring HIV, Treatment Experienced
Eligibility Criteria
Inclusion Criteria:
- Documented HIV infection prior to study entry
- Must be willing to comply with study-mandated evaluations; including not changing their antiretroviral regimen (unless medically indicated) during the study period.
Cohort 1, 2 and 3 (Enrollment Completed)
Cohort 5:
- Must have received HAART therapy, and had undetectable viral loads for at least 1 year.
- HIV-1 RNA < 50 copies/mL obtained within 60 days prior to study entry performed with an ultrasensitive HIV-1 PCR assay.
- CD4+ T cell count >500 cells/mm3
- Heterozygous for the CCR5 delta-32 mutation
- On stable antiretroviral medication (no changes to treatment within 4 weeks of screening and willing to discontinue current antiretroviral therapy during the structured therapy interruption
Cohort 4
- On stable antiretroviral medication (no changes to treatment within 4 weeks of screening and willing to continue on current antiretroviral therapy through week 8 after infusion
- CD4+ T cell count >350 cells/mm3.
- HIV-1 >1,000 copies/mL at screen and not responding to current antiviral therapy (i.e. HIV-RNA plasma levels > 1000 copies/ml after at least 12 weeks of stable, unchanged ARV therapy).
Exclusion Criteria:
- Acute or chronic hepatitis B or hepatitis C infection
- Active or recent (in prior 6 months) AIDS defining complication.
- Any cancer or malignancy within the past 5 years, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin or low grade (0 or 1) anal or cervical dysplasia.
- Current diagnosis of NYHA grade 3 or 4 CHF, uncontrolled angina or uncontrolled arrhythmias.
- History or any features on physical examination indicative of a bleeding diathesis.
- Previous treatment with any HIV experimental vaccine within 6 months prior to screening, or any previous gene therapy using an integrating vector.
- Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents (e.g., interleukin-2, interferon-alpha or gamma, granulocyte colony stimulating factors, etc.) within 30 days prior to enrollment
- Breast-feeding, pregnant or unwilling to use acceptable methods of birth control for 6 months following the last infusion of SB-728-T cells.
- warfarin or any other medication that is likely to affect platelet function or other aspects of blood coagulation during the 2 week period prior to leukapheresis.
- Active drug or alcohol use or dependence
- Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry.
- Recent vaccination or intercurrent illness (within 5 weeks prior to infusion)
- Have an allergy or hypersensitivity to study product excipients (human serum albumin, DMSO and Dextran 40).
- Subjects who are currently taking maraviroc or have received maraviroc within 6 months prior to screening.
Cohort 4 only:
- HIV-1 RNA >1,000 copies/mL at screen and not responding to current antiviral therapy
- CD4+ T cell count >350 cells/mm3
Sites / Locations
- UCLA Center for AIDS Research and Education
- Orange Coast Medical Group
- Quest Clinical Research
- Circle CARE Center, LLC
- Orlando Immunology Center
- Central West Clinical Research, Inc.
- Southwest CARE Center
- Ricky K Hsu, MD, PC
- Gordon Crofoot, MD, PA
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Experimental
Cohort 1
Cohort 2
Cohort 3
Cohort 4
Cohort 5
3 Subjects will receive a single infusion of 0.5-1.0 x 1010 SB-728-T
3 Subjects will receive a single infusion of 2.0 x 1010 SB-728-T
3 Subjects will receive a single infusion of 3.0 x 1010 SB-728-T
Up to 4 HAART failure subjects will receive a single intravenous infusion of 0.5 to 3.0 x 1010 SB-728-T
Up to 20 subjects with heterozygote CCR5 delta-32 mutation will receive a single intravenous infusion of 0.5 to 3.0 x 1010 SB-728-T. Cohort 5 subjects will undergo a structured treatment interruption 2 months following infusion in which their anti-retroviral therapy will be discontinued for 16 weeks. HAART will be reinstituted in subjects whose CD4+ cell counts drop to <350 cells/mm3 and/or whose HIV-RNA increases to >100,000 on three consecutive weekly measurements. At the end of the STI, subjects with a sustained detectable viral load will be reinstituted on HAART. Subjects with HIV RNA levels below the limit of detection will remain off HAART. Subjects with an undetectable viral load will remain off HAART until HIV RNA levels are detectable or their CD4 count drops below 350 cell/mm3 on three consecutive weekly measurements.