Studies

A randomized, open-label, phase 2 study of subcutaneous interleukin-2 (ProleukinR) plus antiretroviral therapy (ART) versus ART alone in patients with HIV infection and CD4+ lymphocyte count greater than 350 cells/mm3

December 31, 1998

Background:

  • Interleukin-2 (IL-2) is an immuno-stimulatory protein, which is central to the appropriate responsiveness of the immune system challenged by invading pathogens
  • Previous studies have shown that the administration of IL-2 in cycles of 5 days every 8 weeks resulted in significant and sustained increases in CD4+ cell counts (Kovacs et al, 1995a)

Objectives: To evaluate the safety. tolerance and efficacy (as measured by changes in CD+ cell counts) of IL-2 in combination with antiretroviral therapy

Study Design

  • The comparative study enrolled 72 patients who were randomized to one of the following two arm
    • Antiretroviral double nucleoside combination therapy alone (n = 36)
    • Antiretroviral double nucleoside combination therapy plus IL-2 q12h for 5 days every 8 weeks (n = 36)
  • The first group of 12 patients received IL-2 at a dose of 1.5 MID q12h for 5 days. This was increased to 4.5 MIU and then 7.5 MIU when at least 9 patients from each group completed the first cycle without significant toxicity
  • Patients initiated with 1.5 or 4.5 MIU and completing 3 cycles were escalated by 3 MIU/cycle to maximum of 7.5 MIU
  • Monitoring at days 1, 2, 3, 4, 5 and 29 of each cycle and also at day 8 in the first cycle for patients receiving IL-2
  • Patients on ART alone monitored at weeks 8, 16 and 24

Result and Discussion:

  • 67% of participants were female
  • Mean baseline CD4+ cell count was 520
  • Adverse events reported include fever, myalgia, malaise and edema
  • There were infrequent in the 1.5 MIU group, but more common at 4.5 and 7.5 MIU
  • No serious adverse events related to study medication were reported
  • At week 16, median CD4+ counts were 1370, 954, 714 and 598 cells/ml in the IL-2 groups 7.5, 4.5 and 1.5 MIU and the ARV alone group, respectively (p < 0.05)
  • Analyses of viral load, T cell subsets and apoptosis are ongoing
  • Despite the smaller body weight of participants in this study compared to those in other studies with IL-2, these preliminary result suggest that the maximum tolerated and effective dose of subcutaneous IL-2 among Thai patients is 7.5 MIU twice dialy
  • Therefore, it is appropriate to consider this as the initial dose in the proposed phase three study

Project no.: HIV-NAT 004 Extension Phase

All patients who complete at least 6 months therapy as part of the above protocol with acceptable compliance are eligible for this extension phase

Study Design

  • Patients randomized to subcutaneous IL-2 in protocol HIV-NAT 004 may continue to receive cycles of IL-2 for this extended one-year of follow-up
  • Administration of IL-2 is on an individual basis according to following guildlines:
    • Objective of ongoing IL-2 therapy is to maintain the individual’s CD4+ cell count at a level at least twice baseline, or 1000 cell/mm3 or greater
    • Cycles of IL-2 therapy continue every 8 weeks for those individuals whose CD4+ cell count is below these levels
    • If CD4 cell count is above these desired levels, the next protocol mandated cycle of treatment may be postponed until the CD4 cell count falls below these levels
    • Follow-up visits are every 4 months (or any interval deemed appropriate for routine patient care)
  • Gradual, stepped dose escalation to a maximum of 7.5 MIU is permitted for those receiving IL-2 at doses of 1.5 MIU and 4.5 MIU
  • Dose reduction is permitted in ceses of intolerance

Results: Interim data analysis pending