Safety Study of IL-7 in HIV-infected Patients (Inspire)
This study will evaluate the safety of a new experimental drug, IL-7, in people with HIV infection. Animal studies have shown that IL-7 can improve the function and number of infection-fighting cells called T lymphocytes, or T cells. If this study shows that IL-7 is safe, additional studies will be done to see if it can improve the function or numbers of T-cells in HIV-infected persons.
HIV-infected persons who have been receiving HAART therapy for at least 12 months before enrolling in the study and have been stable on this treatment for at least 3 months before enrollment may be eligible for this study.
Participants have about 10 clinic visits over 3 months. They receive three injections of IL-7, one injection a week for 3 consecutive weeks. The injections are given as a shot under the skin in the arm or leg. On the day of each injection, the participant stays in the clinic for up to 8 hours or longer for observation and collection of blood samples. Three additional visits (one every 3 months) may be scheduled.
During the study visits the following may be done:
- Medical history, physical examination, blood tests every visit.
- Electrocardiogram (EKG) at study days 0 (day of first dose), 1, 7 (day of second dose), 14 (day of third dose) and 21.
- Chest x-ray study on day 21.
- Blood sample collections at frequent intervals during the first 96 hours after the first dose administration. A catheter (thin plastic tube) may be put into a vein in the arm and left in place to allow several blood samples to be drawn without repeated needle sticks.
- Urine tests several times during the study.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Ph I/IIa Rand Placebo Ctrl, S-Blind Multictr Dose-Esc Study of SC Intermittent Interleukin-7 CYT107 in Chronically HIV-Infected Pts With CD4 T Lymphocyte Counts 101-400 Cells-/mm(3) and Plasma HIV RNA Less Than 50 Copies/mL After at Least 12 M of HAART|
- Safety [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
- Changes in T cell counts, changes in T cell proliferation, changes in expression of CD127 on T cells [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||May 2007|
|Study Completion Date:||July 2010|
|Primary Completion Date:||October 2009 (Final data collection date for primary outcome measure)|
CYT107 vs Placebo (4:1 ratio)
Drug: CYT 107
3 dose levels: 3, 10 and 20µg/kg/week.3administrations
Interleukin 7 (IL-7) is an essential cytokine for the thymic development and the post-thymic survival, expansion and maturation of T lymphocytes in humans. The rationale for using IL-7 as immunotherapy in HIV infection would be to support the expansion, survival and functional properties of T lymphocytes and enhance immune reconstitution. Phase I studies of a previous formulation of rhIL7 in cancer and HIV infected patients have shown that T cell proliferation and expansion can be achieved at doses that are well tolerated. The newly glycosylated form of IL-7 tested in this study has a longer half-life allowing weekly administrations.
This is a phase I/IIa, open label, single arm trial that will test the safety of three subcutaneous injections of IL-7 at three different dose levels (10, 20 and 30 micrograms/kilograms) that will be tested sequentially. Eligible subjects (400 cells/microliters greater than CD4 greater than 101 cells/microliters and VL less than 1000 copies/milliliter, on antiretroviral therapy for at least one year) will be given 3 doses of IL-7 at weekly intervals (day 0, day 7 and day 14). Participants will be followed on days 0, 1, 4, 7, 14, 21 and 28 with additional visits on days 35, 56, and 77 and optional follow up every 3 months thereafter until week 56 (approximately 1 year after enrollment). The three doses will be tested sequentially (10, 20 and 30 micrograms/kilograms per dose) and dose escalation will occur only when safety data from day 28 of the previous dose level participants are complete.
Ten subjects will enroll in each dose level and dose escalation will occur only after all subjects complete four weeks without evidence of dose-limiting toxicities. Secondary end points include a PK study of glycosylated rhIL7 as well as immunologic studies throughout the duration of the study to assess evidence of IL7 biologic activity with markers of T cell proliferation and expression of the alpha chain of the IL7 receptor. This is a multi-center international study sponsored by Cytheris with sites in USA, Canada, Italy and France. Children will be excluded and a separate study will be required in the future after the safety and biologic activity of this agent is established in adults. The study will enroll a total of approximately 30 participants.
|United States, Florida|
|University of Miami School of Medicine|
|Miami, Florida, United States, 33136|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|United States, Ohio|
|Case Western Reserve University|
|Cleveland, Ohio, United States, 44106-2602|
|McGill University Health Center (MUHC)|
|Hopital Henri Mendor-Service d'Immunologie Clinique|
|Hopital Kremlin Bicêtre|
|Kremlin Bicêtre, France|
|Hopital Saint Louis|
|San Raffaele Scientific Institute|
|Study Chair:||Michael Lederman||Case Western Reserve University|
|Study Chair:||Yves Levy||Hopital Henri Mondor|
|Study Chair:||Irini Sereti||National Institute of Allergy and Infectious Diseases (NIAID)|