Efficacy Study of T Cell Vaccination in HIV Infection

HIV Infections Clinical Trial

Official title:

Phase II Study of Efficacy, Tolerability and Safety of CD4-Specific T-cell Vaccine in HIV Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00407836
• Other study ID #: sor444006ctil
• Status: Completed
• Phase: Phase 2
• First received: December 3, 2006
• Last updated: December 1, 2009
• Start date: November 2006
• Est. completion date: November 2008

Study information

• Verified date: November 2006
• Source: Soroka University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical Trial Summary

The hallmark of HIV infection and AIDS is the continuous attrition of CD4 T cells. One of the mechanisms that may account for the CD4 attrition , is autoimmunity against the CD4 T cells, caused by autologous immune cells. Vaccination against autoimmune reactive T cells has been successfully tried in animal models of autoimmune diseases and is now being tried in patients with Multiple Sclerosis. The purpose of the present study is to test this hypothesis in HIV infection. We will vaccinate HIV infected patients in whom specific autoimmune reactivity against CD4 is present , with their own CD4 reactive T cells. Following that, we shall study the patients and find out if the T cell vaccination caused a rise in CD4 T cell levels, and whether it influenced HIV viral load, as well as HIV and CD4 specific immunity.

Description:

The study will be based on forty HIV infected patients, receiving anti retroviral treatment (HAART), with CD4 levels between 150-350 and HIV plasma viral load < 5000, for at least 12 months and despite continuous anti-retroviral treatment. The patients will be randomly divided into two groups, one that will get the T cell vaccination, and the other that will serve as controls. The T cell vaccine will be prepared from autologous T cells that responded by specific proliferation to recombinant CD4, further expanded in vitro by IL-2, and then fixed by glutaraldehyde. Each vaccine portion will consist of 10,000 such cells suspended in saline and given subcutaneously every three months during the first year of the trial. The outcome measures will be CD4 levels, specific immunity to HIV antigens, immune activation profile and HIV plasma viral loads, determined sequentially during the 24 months of the trial. These outcome measures will be compared between the experimental and the control groups, to determine if this mode of treatment is effective in influencing CD4 levels as an additional mode of treatment during HIV infection.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: November 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. CD4 cell counts -from 150 to 450/mm3 and stable for at least 12 months, and treatment with HAART for at least 6 months.

2. Positive cell proliferation assay to CD4 molecule

3. Low HIV viral load (<400 - 5000 copies/ml) for at least 12 months

4. No change of antiretroviral treatment for at least 6 months

5. Signed informed consent

Exclusion Criteria:

1. Concomitant immunosuppressive or antineoplastic treatment as well as chronic systemic glucocorticoid therapy.

2. Pregnancy and women without any efficacious contraception.

3. Clinically relevant liver disease (AST and/or ALT >2,5x upper limit of normal range, or total bilirubin > 3,5 mg/dl).

4. Serum creatinine >1,8mg/dl or creatinine clearance <30ml/min.

5. Patients who cannot fully understand the treatment protocol or are unable to sign the informed consent.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Infection

Intervention

Biological:
• T cell vaccination
Approximately 10-20 million glutaraldehyde fixed CD4 responsive autologous T cells in 1-2 ml, per vaccine injection.
• T cell vaccination
Approximately 10-20 million autologous CD4 reactive T cells per each vaccine injection

Locations

Country	Name	City	State
Israel	Soroka Medical Center	Beer Sheba

Sponsors (1)

Lead Sponsor	Collaborator
Soroka University Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (2)

Abulafia-Lapid R, Bentwich Z, Keren-Zur Y, Cohen IR, Atlan H. T-cell vaccination against anti-CD4 autoimmunity in HIV-1 infected patients. J Clin Virol. 2004 Dec;31 Suppl 1:S48-54. — View Citation

Abulafia-Lapid R, Mayan S, Bentwich Z, Keren-Zur Y, Avbramovitz Y, Cohen IR, Atlan H. T-cell vaccination against anti-CD4 autoimmunity in HIV-1 subtypes B and C-infected patients--an extended open trial. Vaccine. 2005 Mar 18;23(17-18):2149-53. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CD4 T cell levels		one year follow up	No
Primary	HIV plasma viral load		one year follow up	No
Primary	Clinical HIV infection		one year follow up	No
Secondary	HIV specific immune responses		One year follow up	No
Secondary	CD4 specific responses		One year follow up	No
Secondary	Immune profile		One year follow up	No