Trial ID Number: CLI-107-06

Title: A Phase I/IIa Randomized Placebo Controlled, Single-Blind Multicenter Dose-Escalation Study of Subcutaneous Intermittent Interleukin-7 CYT107 in Chronically HIV-Infected Patientswith CD4 T-Lymphocyte Counts Between 101-400 Cells/Mm3 and Plasma HIV RNA< 50 copies/mL after at Least 12 Months of HAART.

Trial Name: INSPIRE (INvestigational Study of Placebo versus IL-7
in haaRt-trEated patients)
Countries: United States, Canada, France and Italy
Status: Ongoing
Link to Clinical Trial: Clinical Trials.Gov

About the INSPIRE HIV Study
The HIV trial (CLI-107-06) is a randomized placebo controlled, single-blind multi-center dose-escalation study of chronically HIV-infected patients with CD4 T-lymphocyte counts between 101-400 cells/mm3 and plasma HIV RNA < 50 copies/mL after at least 12 months of Highly Active Anti-Retroviral Therapy (HAART). The dose escalation scheme is designed to establish the safety of biologically active doses of CYT107, to document the residual CD4 increase achieved at 3 months (“targeted sustained activity”) and to define a dose and schedule for phase II investigation.  In addition, potential biologic Dose Limiting Toxicities (DLT), unique to IL-7 (such as viral reactivation or immunogenicity) will be sought.

Michael M. Lederman, MD, the Scott R. Inkley Professor of Medicine and Director of the Case Western Reserve University/University Hospitals Center for AIDS Research, Cleveland, Ohio, will chair the study along with co-chairs Irini Sereti, MD, US National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, and Yves Levy, MD, PhD, Service d’Immunologie Clinique, Hôpital Henri Mondor, Créteil, France. 

Results of two promising Phase I studies of Cytheris’ IL-7 in HIV patients, one conducted by Dr. Levy’s team and the other by the US National Institutes of Health/AIDS Clinical Trials Group (ACTG), were reported at the 2007 Conference on Retroviruses and Opportunistic Infections (CROI) held in Los Angeles. Dr. Levy also presented long-term follow-up results (at week 48) of the French study at the 2008 Conference on Retroviruses and Opportunistic Infections (CROI) held in Boston. This study has since been published in Lévy Y, et al Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment. J Clin Invest. 2009, Vol. 119, No. 4: 997-1007.

Trial ID Number: CLI-107-13

Title: An open-label, multicenter study of subcutaneous intermittent recombinant Interleukin-7 (CYT107) in chronically HIV-infected patients with CD4 T-lymphocyte counts between 101-400 cells/mm³ and plasma HIV RNA< 50 copies/mL after at least 12 months of HAART.

Trial Name: INSPIRE 2
Countries: United States, Canada
Status: Ongoing
Link to Clinical Trial:

About the INSPIRE 2 HIV Study
INSPIRE 2 is an open-label, multicenter study of subcutaneous intermittent recombinant Interleukin-7 (CYT107) in chronically HIV-infected patients with CD4 T-lymphocyte counts between 101-400 cells/mm3 and plasma HIV RNA< 50 copies/mL after at least 12 months of HAART. The study will be conducted across4 investigative sites in the United States and Canada.

This phase IIa confirmatory study is designed to further demonstrate the biological activity of CYT107 and provide data that will help in the design of phase IIb/III trials. The study objectives include characterization of CYT107 pharmacokinetics and pharmacodynamics in patients with moderate to severe lymphopenia, delineation of the relationship between CYT107 dose and biological activity, and confirmation of the relevance of the treatment schedule evaluated in the first INSPIRE study reported in an oral late breaker session at the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) held September 12-15, 2009, in San Francisco, CA (Abstract H-1230a).

The primary objective of the study is to determine in detail the biological activity and PK profile of CYT107 (20 µg/kg/week), during a 12 week study period with a follow up period of up to 1 year, in an HIV-infected cohort with CD4 counts of 101-400 cells/µL. The dose of 20 µg/Kg/week that will be evaluated in this study has shown a good safety profile and biological activity in the first INSPIRE study CLI-107-06) conducted in a similar population.

Secondary objectives are:

• To characterize the pharmacokinetics and pharmacodynamics of CYT107 in the targeted population.
  
  
• To further evaluate the safety profile established with CYT107 at 20µg/kg. Safety assessments will include a close monitoring of the impact OF CYT107 on HIV RNA viral load and immunogenicity.
  
  
• To further evaluate the immunological effects established with CYT107 at 20µg/kg.
  
  
• To document the potential sustained CD4 increase achieved at D21, D28, Weeks 9 and 12 (“targeted sustained activity”)
  
  
• To document safety and sustained CD4 increase quarterly until the end of the first year.
  
  
• To document other immunological properties of IL-7, (i.e. T-cell homing within the lower GI tract).