Date: 2011-03-01
Type of information:
phase: 2a
Announcement: results
Company: Cytheris (France)
Product: CYT107 (recombinant interleukin-7)
Action mechanism: Recombinant human interleukin-7 (CYT107) is a critical immune-modulator for immune T-cell.
Disease: chronically HIV infected persons
Therapeutic area: Infectious diseases
Country:
Trial
details: INSPIRE 2 is an open-label, multicenter Phase IIa study of CYT107 (IL-7) in chronically HIV infected persons with CD4 T-cell counts between 101-400 cells/mm3 and plasma HIV RNA< 50 copies/mL. Twelve patients were enrolled and received 20 mcg/kg/week of CYT107 for 3 weeks. All were evaluated at the planned primary end point at week 12 (CD4 expansion). The 12 enrolled patients received three weekly injections of CYT107 that were clinically well tolerated and without serious adverse events. Seven patients had transient increases in HIV RNA values (< 500 copies/mL). Median CD4 and CD8 T-cell counts were 272 and 554 cell/mm3 at baseline, increasing to 679 and 986 cells/mm3 at week 12, respectively. CYT107 also decreased PD-1 frequency, a marker of T cell exhaustion, in both CD4 and CD8 T-cells at W12 (p=0.008 and p=0.02). The decrease of PD-1 frequency on CD4 T-cells occurred as early as two weeks following the last administration of CYT107. Twelve patients underwent immunophenotypic analyses of cryopreserved PBMC by flow cytometry at baseline and at week 12. A sustained increase of the gut homing receptor alpha 4beta 7 integrin frequency on peripheral CD4 and CD8 T-cells was noted (1.4-fold in both) as early as day seven post first CYT107 administration (t test; p<0.002), with a peak increase at day 14 (p=0.0001). At week 12 ?4ß7 remained elevated on peripheral CD8 (p=0.009) on T-cells. A subset of 4 patients underwent rectosigmoid biopsies both at baseline and between weeks 10-24. Mucosal gut biopsy analysis showed an increase in both CD4 T-cell frequency and counts.
Latest
news: The findings in the current study confirm previously reported results in SIV infected monkeys showing the ability of IL-7 treatment to drive T-cells to the gut mucosa and facilitate their expansion. The study confirms IL-7’s potential for T-cell expansion, and also showed its ability to send T-cells to the gut mucosa where it triggers local T-cell expansion. Numerous experimental and clinical studies confirm that T-cell reconstitution in the gut is critical for restoring control over the HIV virus. The study therefore provides further evidence suggesting that administration of IL-7 may have an important effect on immunologic recovery in HIV-infected patients whose HAART regimens have been unsuccessful in restoring CD4 T-cells to a stable level. The sustained immunological efficacy suggests that a short course of IL-7 treatment may provide an important avenue for enhancing the immune system and inducing broad spectrum proliferative activity of CD4 and CD8 T-cells in the blood, lymph nodes and small intestine, a key therapeutic effect in achieving long term disease stability in HIV-infected patients.
