A Phase I Evaluation of the Safety and Biologic Activity of TXA127 in HIV-Infected Subjects With CD4+ T-Lymphocyte Counts Less Than 250 Per mm3 Who Have Responded to HAART

This is a Phase I, single institution, open-label, within-dosing-cohort-schedule randomized, dose escalation study of TXA127 in HIV-infected subjects with CD4+ T-lymphocyte counts less than 250 per mm3 who have responded to highly active retroviral therapy (HAART). The study has been designed to determine the maximum tolerated dose (MTD) of TXA127 in this subject population. This study will also obtain safety and biologic activity information about the subcutaneous injection of TXA127.

Five escalating dosing cohorts will be examined to determine the MTD. The first four dosing cohorts will receive 50, 100, 200 and 300 mcg/kg of TXA127 by subcutaneous injection daily for 14 days, followed by 14 days without treatment. These 28 days will be defined as one cycle. The cycle of therapy will be repeated once, for a total of two courses of treatment. The 5th dosing cohort will receive 300 mcg/kg of TXA127 by subcutaneous injection daily for 28 days, then 14 days without treatment followed by an additional 28 days of TXA127 administration. Dose escalation to the next cohort of subjects will be permitted to the next higher dosing level provided the following criteria have been met.

A standard Simon Phase I dose escalation trial has been proposed. The MTD will have been exceeded if the proportion of subjects that develops the same or similar study-drug-related, DLT in an assigned dosing schedule equals 2/2, 2/3, 2/4, 2/5, and 2/6 subjects. The MTD is defined as the largest dose that <2 of 6 subjects experiences a DLT. Dose-limiting toxicity is defined as a study-drug-related grade 3 or 4 adverse event (AE).