Interluekin-7 to Treat HIV-Infected People Receiving Antiretroviral Treatment

HIV Infections Clinical Trial

Official title: A Phase I, Randomized, Placebo-Controlled, Double-Blind Study Evaluating the Safety of Subcutaneous Single Dose Interleukin-7 in HIV-1-Infected Subjects Who Are Receiving Antiretroviral Treatment (A5214)

Status Completed

Clinical Trial Summary

This study will evaluate whether interleukin-7 (IL-7) a drug similar to the natural IL-7 protein produced by the body, is safe to use in people infected with HIV. IL-7 is important in immune system function. In humans, it can extend the life of immune cells called T-cells and increase their function and maturation; in mice, it can speed up immune system recovery following chemotherapy of transplantation; and in monkeys, it can make T-cells increase in numbers. If this study shows that IL-7 is safe, other trials will determine if it can improve the numbers or function of T-cells in HIV-infected people.

Patients 18 years of age and older with HIV infection who have been taking anti-HIV medications for at least 12 months, whose CD4 counts are at least 100 cells/microliter, and whose viral load is no more than 50,000 copies/milliliter may be eligible for this study. Candidates are screened with a physical examination, blood and urine tests, including a blood test for HLA type (a genetic test of markers of the immune system), chest x-ray, electrocardiogram, and ultrasound of the spleen.

Participants undergo the following tests and procedures during 9 visits, as follows:

Pre-entry visit

• Brief physical examination, including examination of lymph nodes and spleen.

• Medical history, including questions about current and past medications.

• Urine pregnancy test for women who are able to become pregnant.

• Blood draw for viral load, immune responses, and other routine safety tests.

Entry visit

• Complete physical examination, including examination of lymph nodes and spleen.

• Routine urine test and urine pregnancy test for women who are able to become pregnant.

• Blood draw for viral load, immune responses, and other routine safety tests.

• IL-7 dosing. Participants are randomly assigned to receive one of five doses of IL-7 (3, 10, 30, 60 or 100 micrograms per kilogram of body weight) or placebo (a salt solution that does not contain IL-7). The dose may be given in one or more injections, with higher doses possibly requiring as many as seven or eight injections. The injections are given subcutaneously (under the skin), usually in the arm or leg. After the injection, patients are monitored closely for 12 hours for skin or allergic reactions. Blood is drawn before the injection and again at 0.5, 1, 1.5, 2, 2.5, 4, 8 and 12 hours after the injection to check blood levels of the study medication.

Follow-up visits

Patients come to the clinic 7 times during follow-up-every day for the first 4 days after the injection, then at 14 days, 4 weeks, and 8 weeks after the injection. At most study visits, patients have the following procedures:

• Brief physical examination, including examination of lymph nodes and spleen.

• Routine urine test and urine pregnancy test for women who are able to become pregnant.

• Blood draw for viral load, immune responses, and other routine safety tests.

• Blood test to measure the amount of study medication in the blood 1, 2, and 3 days after the injection

• Electrocardiogram 1 day after the injection

Clinical Trial Description

Interleukin 7 is an essential cytokine for the thymic development and the post-thymic survival, expansion and maturation of the T lymphocytes in humans. Therapeutic use of IL7 in mouse models has shown enhancement of immune reconstitution after chemotherapy or bone marrow transplantation. 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. More specifically, IL7 may provide the means to support CD4 expansions in patients with good viral suppression but persistent low CD4 counts (immunologic non-responders) or in patients who have no available antiretroviral options. Finally, given the role of IL7 in T cell memory maturation and survival, IL-7 may be a promising vaccine adjuvant.

Studies of rhIL7 in non-human primates have shown that T cell proliferation and expansion can be achieved at doses that are well tolerated without significant toxicity. A safety study in cancer patients is currently ongoing at the NCI. A5214 (Pleiades) will be the first study of rhIL7 to evaluate the safety of a single subcutaneous injection in HIV infected adults. Eligible subjects (CD4 greater than 100 cells/micro l and VL less than 50,000 copies/ml, on antiretroviral therapy for at least one year) will be stratified by viral load (less than 50 or 50-50,000 copies/ml) and will be randomized 3:1 to receive rhIL7 or placebo.

Pleiades is a phase I, double-blind trial that will test the safety of a single subcutaneous injection of IL-7 at 5 different doses (3, 10, 30, 60 and 100 micro g/kg) tested sequentially. Four 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 as reviewed by the safety monitoring committee. Secondary end points include a PK study of rhIL7 as well as immunologic studies throughout the duration of the study to assess evidence of IL7 biologic activity with markers of T cell activation, proliferation and differentiation as well as expression of the alpha chain of the IL7 receptor.

This is an Adult AIDS Clinical Trial Group (AACTG) study and the NIAID will participate as a site. The NIAID site will follow all NIAID IRB reporting requirements and all grade 1 and 2 toxicities will be included in the annual review. 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 40-80 patients followed for a total of eight weeks, with approximately 15-20 anticipated to enroll in our site. ;

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV
• HIV Infections

• NCT number: NCT00105417
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: March 2005
• Completion date: May 2006