Clinical protocol. A phase 1 open-label clinical trial of the safety and tolerability of single escalating doses of autologous CD4 T cells transduced with VRX496 in HIV-positive subjects.

摘要: The proposed study is a Phase I trial to evaluate HIV-based lentiviral vector carrying an antisense sequence targeted HIV in the treatment of infection. primary objective this determine safety and tolerability with autologous CD4+ T cells modified (transduced) ex vivo VRX496 when administered HIV-infected patients. completely gutted does not code for any viral proteins. contains envelope (env) gene. directly interferes wild-type (wt-HIV) expression via anti-env transduced CD4 that become infected wt-HIV. Expression anti-HIV env from transcript would target wt-HIV RNA destroy it, hence, decrease productive replication cells. clinical goal approach loads promote cell survival vivo. Data vitro studies suggest vectors such as could potentially reduce individuals thus delay onset AIDS while promoting providing immune system better chance control Additionally, preliminary results experiments SCID mice (mice transplanted human cells) indicate implanted into do elicit overt adverse effects. patients (CD4 count >200/mm3, discontinued HAART therapy) will undergo leukoapheresis subsequent isolation. Patient be vector, expanded 8-11 days, then reintroduced patient. Each subject receive single intravenous injection infused over 30 minutes; subjects examined 24, 48, 72 hours post-injection weekly 4 weeks. Patients one four different ascending doses (1 x 10(9), 3 1 10(10), X 10(10) cells/patient). Doses independent, sequential cohorts Groups escalating at 6-week intervals after has been demonstrated previous group. Follow-up examinations conducted 1, 3, 6 months post-injection. Long term follow-up including RCR testing performed.