Repeat Doses of SB-728mR-T After Cyclophosphamide Conditioning in HIV-Infected Subjects on HAART

A Phase 1/2, Open-Label Study to Assess the Safety and Tolerability of Repeat Doses of Autologous T-Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases in HIV-Infected Subjects Following Cyclophosphamide Conditioning

The purpose of this study is to evaluate the safety and tolerability of repeat doses of T-cell immunotherapy (SB-728mR-T) following cyclophosphamide conditioning.

CCR5 is a major co-receptor for HIV entry into T-cells. Disruption of CCR5 by zinc finger nuclease (SB-728mR), blocks HIV entry into the T-cells, therefore, protects the T-cells from HIV infection. Safety (primary outcome) and anti-viral effect (secondary outcome) of zinc finger nuclease-mediated CCR5 disrupted autologous T-cells (SB-728mR-T) will be evaluated in the study.

Inclusion Criteria:

• Male or female, 18 years of age or older with documented HIV diagnosis.
• Must be willing to comply with study-mandated evaluations; including discontinuation of current antiretroviral therapy during the treatment interruption.
• Initiated HAART therapy within (≤) 1 year of HIV diagnosis or suspected infection.
• Undetectable HIV-1 RNA for at least 2 months prior to screening and at screening.
• CD4+ T-cell count ≥500 cells/µL.
• Absolute neutrophil count (ANC) ≥ 2500/mm3.
• Platelet count ≥ 200,000/mm3.

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.
• Received 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 within 30 days prior to screening.
• Use of Aspirin, dipyridamole, 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.
• Currently participating in another clinical trial or participation in such a trial within 30 days prior to screening visit.
• Currently taking maraviroc or have received maraviroc within 6 months prior to screening.