Date: 2011-11-08
Type of information:
phase: 1-2a
Announcement: Results
Company: Cytheris (France)
Product: CYT107 (Recombinant human interleukin-7)
Action mechanism: Recombinant human interleukin-7 (CYT107) is a critical immune-modulator for immune T-cell recovery and enhancement. As a growth factor and cytokine physiologically produced by marrow or thymic stromal cells and other epithelia, IL-7 has a critical and, at some steps, a non-redundant stimulating effect on T lymphocyte development, notably on thymopoïesis and, downstream from the thymus, on homeostatic expansion of peripheral T-cells.
Disease: hepatitis C
Therapeutic area: Infectious diseases
Country:
Trial
details: ECLIPSE 2 is an open-label, dose-escalating study (3, 10 and 20 microg/kg/week).
CYT107 was administered subcutaneously, one injection per week for 4 weeks (D0 to D21), as an add-on therapy to 24 or 48 weeks of SOC, peginterferon and ribavirin. SOC was initiated 9 weeks (median) before CYT107. Six patients were included at each dose level and 6 more if at least 2 patients showed a HCV RNA drop > 2 logs. Patients <18 years, with liver cirrhosis, abnormal bilirubin or AP, HIV or HBV coinfection were excluded. Interim results reported at AASLD focus on the 16 patients treated at 3 or 10 microg/kg/wk.
Latest
news: Cytheris has announced that data from an interim analysis of its ECLIPSE 2 Phase I/IIa study indicate that treatment with four weeks of the Company’s investigative immune-modulator, recombinant human Interleukin-7 (CYT107), added to peginterferon and ribavirin (SOC) in genotype 1 and 4 treatment experienced patients defined as nonresponders to SOC, induces a broad immune response associated with HCV viral clearance in genotype 1 and 4 treatment experienced patients defined as nonresponders to SOC. In chronic HCV patients defined as non responders to SOC, CYT107 treatment was safe and expanded both CD4 and CD8 T cells, an effect known to provide an efficient and stable immune response. CYT107 also induces a normalization of the diversity of the TCR repertoire. At 10 ?g/kg/wk, this effect was associated with an antiviral effect and disappearance of serum HCV RNA in patients nonresponsive to SOC. These promising results suggest the need for future studies combining direct acting antivirals (DAAs) and CYT107 which act through immune restoration in order to achieve complementary immune and direct antiviral effect to achieve a rapid elimination of HCV RNA under a shortened regimen. In fact, as noted above, 5 of these resistant patients among the 12 treated patients quickly became HCV RNA negative after adding CYT107 to SOC.
The data were presented during a late breaker poster session (Abstract #LB-9:
Four weeks of IL-7 (CYT107) added to peginterferon and ribavirin (SOC) induces a broad immune response associated with HCV viral clearance in genotype 1 and 4 treatment experienced patients defined as nonresponders to SOC.
Interim results reported at AASLD focus on the 16 patients treated at 3 or 10 micro/kg/wk.
During the study, there was only one serious adverse event (AE) that did not lead to study drug discontinuation. There were no other SAEs, DLT orclinically relevant abnormalities in biological parameters related to CYT107 treatment. 78.6% of Aes were of grade less than 1, primarily injection-site reactions, and no neutralizing IL-7 antibodies were detected.
At D56, consistent with CYT107 results in HIV, CYT107 (10 microg/kg/wk) induced (median values):
• A T cell increase +341 CD4/microl (+168%) and +209 CD8/microl (+179%) more than correcting the initial pre-CYT107-SOC induced lymphopenia (-147/?L CD4)
• A broadening of the T cell receptor repertoire (TCR) diversity (+25%) in the 4 patients with low diversity at D0 (45%)
• An increased number of CD3 expressing the alpha4beta7 receptors (+73%)
These increases in T cell counts, diversity and functionality were associated with HCV viral elimination at Week 12 in 1/6 patients treated at 3?g/kg and in 5/12 patients treated at 10 ?g/kg. At CYT107 initiation, all 6 responding patients had a moderate viral load (<4.5 log/mL), showed an increased rate of viral clearance (+25%), and remained undetectable (median current follow up: 11 months).
