Safety Study of TXA127 to Elevate CD4+ T-Lymphocyte Counts in HIV-Infected Patients on Stable HAART Therapy

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.

Four escalating dosing cohorts will be examined to determine the MTD. The four dosing
cohorts will receive 50, 100, 200 and 300 mcg/kg of TXA127 by subcutaneous injection daily
for 14 days then 14 days without treatment. The 28 days will be defined as one cycle. The
cycle of therapy will be repeated once, for a total of two courses of treatment. Between 2
and 6 subjects will be enrolled in a dose cohort depending on the incidence of dose-limiting
toxicities (DLT)among the within-cohort subject population. Dose escalation to the next
cohort of subjects will be permitted if no more than one subject in a dose cohort develops a
DLT considered to be probably or definitely related to the investigational drug.

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).