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INSPIRE Study: Effects of r-hIL-7 on T Cell Recovery and Thymic Output in HIV-infected Patients Receiving c-ART - Interim Analysis of a Phase I/IIa Multicenter Study
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Reported by Jules Levin
ICAAC Sept 11-15 2009 San Francisco
Y.LEVY1, I. SERETI2, G. TAMBUSSI3, J-P ROUTY4, J-F DELFRAISSY5, J-M MOLINA6, M FISCHL7, T CROUGHS8, R-P SEKALY9, M LEDERMAN10
1Hosp H.Mondor, Creteil, FR; 2NIAID/NIH, Bethesda, MD, US;3San Raffaele Scientific Institute, Milano, IT 4McGill Univ Health Center, Montreal, CA; 5Hosp Kremlin Bicetre, FR; 6Hosp St-Louis, Paris, FR ; 7 University Miami School of Medecine, Miami,Fl, US; 8Cytheris, FR ; 9 NIML, Montreal, CA ; 10Case Western Reserve University, Cleveland, OH, US
from Jules: As I said before I went to the microphone and mentioned we just spent 7 yrs and $30 millions dollars to evaluate IL-2 to find no clinical benefit and perhaps toxicities so how will they proceed. In response Levy and a representative from the company said they plan to design a study using different parameters, outcomes - that is shorter-term outcomes, and that IL-7 is different than IL-2. We'll see what the FDA says.
ABSTRACT
Background: r-hIL-7 therapy increases T cell counts in chronic HIV-infected patients (pts). Effects of rh-IL-7 on thymic output in these pts has not been explored. Here we report interim results at week 12 from the first 2 dose levels of a new phase I/IIa study performed with a glycosylated form of IL-7 (CYT107).
Methods: Chronically HIV-infected pts with 101-400 CD4 cells/mm3 and plasma HIV RNA< 50 cp/mL while on ART received 3 weekly subcutaneous injections of CYT107. 3 doses were tested: 10, 20 or 30 µg/kg (8 pts CYT107 vs 2 placebo per dose). T cell subsets and thymopoiesis (RTE and sj/ßTRECs ratio quantification) analyses were performed.
Results: No clinical or laboratory side effects > grade 2 recorded. At 20µg/kg, 4 pts had a transient increase of HIV RNA values (<500 cp/mL in 3 of 4 and 1023 cp/mL in 1). Activity of CYT107 is shown below:
Total and naïve CD4 and CD8 increases are statistically significant vs placebo group (P<0.005). 1/7 and 5/8 of pts experienced CD4 counts > 500 cells/mm3 at week 12 (P<0.005) at the 10 and 20mcg/kg dose respectively.
Conclusions: A 3 injection cycle of rh-IL-7 induces a dose dependent and sustained increase of CD4 T cells. A higher proportion of pts experienced CD4 counts > 500 cells/mm3 and a trend toward higher thymic output at 20mcg/kg.
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