This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Some individuals who maintain HIV control fail to significantly increase their CD4 T cells. This is likely to be due to thymic dysfunction. Palifermin is a recombinant human keratinocyte growth factor that has been shown to increase thymic output in animals and is licensed to prevent mucositis in stem-cell transplant recipients. It does have some serious side effects (i.e., rash and oral abnormalities such as impaired taste). A5212 is a double blind, phase II study designed to evaluate whether palifermin in at least one of three IV bolus doses will be effective at increasing CD4+ lymphocyte counts through enhanced thymopoiesis in HIV-1-infected subjects with suppressed viral loads but inadequate CD4+ T-cell counts. The primary endpoint of the study is the change of CD4+ T-lymphocyte counts from baseline to week 12. A total of 96 subjects will be enrolled into the trial, with 24 subjects randomized into 4 treatment arms: Arm A: palifermin placebo IV bolus daily for 3 days Arm B: palifermin 20 mcg/kg IV bolus daily for 3 days Arm C: palifermin 40 mcg/kg IV bolus daily for 3 days Arm D: palifermin 60 mcg/kg IV bolus daily for 3 daysTo maintain study product blinding, each subject will receive three IV bolus doses of palifermin or palifermin placebo on each of 3 consecutive days: day 1 (Entry), day 2, and day 3. Subjects will be followed on study for a total of 24 weeks. Significance: This is a proof of concept study. Approach: This is a dose-finding study that is relatively short term in treatment and has intensive immunologic studies of thymic function. Hypothesis: Palifermin (recombinant human keratinocyte growth factor [rHuKGF]) in at least one of three doses will be effective in increasing CD4+ lymphocyte counts through enhanced thymopoiesis in HIV-1-infected subjects with suppressed viral loads but inadequate CD4+ cell counts. Primary Objective: To demonstrate a greater rise in absolute CD4+ lymphocyte count with one of the three dose regimens of palifermin compared with placebo at the week 12 time point. Secondary Objectives: To demonstrate a greater rise in na ve CD4+ cell counts with palifermin treatment compared with placebo.
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