Safety Study of IL-7 in HIV-infected Patients (Inspire)

NCT00477321 | Completed Phase 1 DMC

• 1 other identifier: CLI-107-06
• Study Type: interventional
• Target: 30
• Locations: 4 countries
• Sites: 8

Brief Summary

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.

Conditions

HIV Infections; Lymphopenia

Keywords

Interleukin 7; Immune Reconstitution; T Cell Turnover; CD4 Lymphenia; Immune-Based Therapies; HIV Infection

Outcome Measures

Primary Outcomes (1)

• Safety

  12 weeks

Secondary Outcomes (1)

• Changes in T cell counts, changes in T cell proliferation, changes in expression of CD127 on T cells

  12 weeks

Study Arms (1)

CYT107

EXPERIMENTAL

CYT107 vs Placebo (4:1 ratio)

Drug: CYT 107

Interventions

CYT 107 DRUG

3 dose levels: 3, 10 and 20µg/kg/week.3administrations

Also known as: CYT107, Interleukin-7, rhIL-7

CYT107

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 18 years
• HIV1 infection as documented by any licensed ELISA test kit and confirmed by Western Blot at anytime prior to study entry.
• On HAART for at least 12 months, and stable on treatment for at least 3 months prior to enrollment. HAART is defined as any protease inhibitor (PI or without ritonavir) + 2 nucleoside reverse transcriptase inhibitors (NNRTI) or any non nucleoside reverse transcriptase inhibitors (NNRTI) + 2 NRTIs. NOTE: RTV-boosted PIs will be considered one antiretroviral drug.
• CD4 cell counts greater than or equal to 101 and less than or equal to 400 cells/mm(3) on at least three consecutive measurements (including the screening value) within the previous 6 months prior to enrollment.
• Patient with CD4 cell counts greater than or equal to 101 and less than or equal to 150 cells/mm(3) with a NADIR greater than or equal to 50 if the NADIR was reached less than 24 months prior to enrollment.
• Plasma HIV RNA less than 50 copies/mL on at least two consecutive measurements (including the screening value) within the previous 6 months prior to enrollment.
• No AIDS-defining illness (Category C) within the last 6 months prior to enrollment
• Normal thyroid-stimulating hormone (TSH).
• Ability to understand and give written informed consent.

You may not qualify if:

• Dual or single antiretroviral therapies with nucleoside analogs.
• Enfuvirtide or any other investigational antiretroviral agent.
• Any planned or probable modification of the antiretroviral treatment during the 3-month study period.
• Current or recent history (less than 30 days prior to screening) of a viral, bacteria, parasitic or fungal infection requiring systemic treatment and/or hospitalization.
• Positive PPD (North American subjects, except those who have received and completed INH prophylaxis).
• Any serious illness requiring systemic treatment and/or hospitalization until the patient either completes therapy or is clinically stable on therapy, in the opinion of the principal investigator, for at least 28 days prior to study entry.
• Any history of malignancy (except basal carcinoma of the skin) including any hematologic malignancy or AIDS defining malignancy, such as lymphoproliferative disorder or Kaposi's sarcoma. (Patients with Kaposi's sarcoma limited to the skin that disappeared while on HAART therapy, and without requiring any other systemic therapy, 1 year prior to study entry will be eligible to participate).
• Any history of HIV related encephalopathy.
• Hepatitis B or C (positive HBs Ag or positive anti HBc antibodies with a detectable HBV DNA viral load or positive anti HCV antibodies with a detectable HCV RNA viral load). Patients who became negative to HBV DNA or HCV RNA following an antiviral treatment should not be enrolled.
• HIV-2, HTLV-1 and HTLV-2 seropositivity.
• Pregnant or lactating women. Women of childbearing potential must have a negative serum or urine pregnancy test within 1 week prior to study entry.
• Refusal or inability to practice contraception during therapy regardless of the gender of the patient.
• Participation in another investigational interventional study during this study or within the last 6 months.
• Family history of sudden cardiac death.
• Corrected QT interval (QTc) prolongation defined as a QTc greater than or equal to 470 ms or a prior history of cardiovascular disease, arrhythmias, or significant ECG abnormalities.

Sponsors & Collaborators

• Cytheris SA: lead

Study Sites (8)

University of Miami School of Medicine

Miami, Florida, 33136, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106-2602, United States

Location

McGill University Health Center (MUHC)

Montreal, Canada

Location

Hopital Henri Mendor-Service d'Immunologie Clinique

Créteil, France

Location

Hopital Kremlin Bicêtre

Le Kremlin-Bicêtre, France

Location

Hopital Saint Louis

Paris, France

Location

San Raffaele Scientific Institute

Milan, Italy

Location

Related Publications (3)

• Stebbing J, Gazzard B, Douek DC. Where does HIV live? N Engl J Med. 2004 Apr 29;350(18):1872-80. doi: 10.1056/NEJMra032395. No abstract available.

  PMID: 15115833 BACKGROUND

• Battegay M, Nuesch R, Hirschel B, Kaufmann GR. Immunological recovery and antiretroviral therapy in HIV-1 infection. Lancet Infect Dis. 2006 May;6(5):280-7. doi: 10.1016/S1473-3099(06)70463-7.

  PMID: 16631548 BACKGROUND

• Douek DC, Picker LJ, Koup RA. T cell dynamics in HIV-1 infection. Annu Rev Immunol. 2003;21:265-304. doi: 10.1146/annurev.immunol.21.120601.141053. Epub 2001 Dec 19.

  PMID: 12524385 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

HIV Infections; Lymphopenia

Interventions

Interleukin-7; efineptakin alfa

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• 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)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2007
• First Posted: May 23, 2007
• Study Start: May 1, 2007
• Primary Completion: October 1, 2009
• Study Completion: July 1, 2010
• Last Updated: October 18, 2012

Record last verified: 2012-10

Locations

CA (1); IT (1); US (3); FR (3)