Re-boosting of HIV-1 Infected Subjects With Vacc-4x

Study Overview
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Brief Summary
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During the course of HIV infection the number of CD4 cells decreases, resulting in a reduced immunological response and eventually immune deficiency. Vacc-4x is a peptide-based HIV immunotherapy vaccine and is anticipated to strengthen the immune system's response to HIV. All patients participating in this trial have previously received the vacc-4x vaccine in order to reduce the amount of HIV-1 virus in the blood and increase the immune response. The primary objective of this study is to evaluate if a re-boost with Vacc-4x could further reduce the amount of HIV-1 virus and increase the immune response.

Detailed Description
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Human immunodeficiency virus (HIV) infects the cluster of differentiation 4 (CD4) subset of T-cells that are critical for initiating immune responses to infection. The level of CD4 cells in the blood is a marker of a patient's immunological status. During the course of an HIV infection, the number of CD4 cells decreases, resulting in reduced immunological responsiveness and ultimately immune deficiency. Current management of an HIV infection includes antiretroviral therapy (ART). The advent of effective ART in 1996 led to a profound decrease in type 1 HIV (HIV-1)-associated morbidity and mortality in developed countries where ART has been available. Despite the ability of ART to inhibit HIV-1 replication, it cannot cure infection, making ART a lifelong treatment that requires sustained compliance and imposes significant individual and societal financial burdens on healthcare services. Furthermore, ART side effects (e.g., metabolic toxicity and stigmatizing body fat redistribution) often require medication that further increases the inconveniences and financial burdens of HIV management. Of additional concern is the emergence of viruses resistant to ART that can result in treatment failure. Vacc-4x is a peptide-based HIV therapeutic vaccine. The primary objective of Vacc-4x therapeutic vaccine is to strengthen the immune system's response to HIV p24. ART dramatically reduces the level of virus in circulation in the body, thereby allowing the immune system to focus on the therapeutic vaccine that is administered. ART also allows for the generation of new naïve CD4 cells that can be triggered by the therapeutic vaccine to generate new immune responses to HIV-1. Subjects are therefore immunized with Vacc-4x in the presence of ART to generate new HIV-specific immune responses that can sustain immunological fitness for prolonged periods when patients are removed from ART. It is likely that periodic boosting on ART will be required to sustain the immunotherapeutic effect - in this way ART may become an intermittent therapy. This study is a follow-up, re-boosting study of Study CT-BI Vacc-4x 2007/1 (EudraCT Number 2007-006302-13) performed in US and Europe (UK, Germany, Spain and Italy). All subjects to be included have been given a therapeutic immunization with Vacc-4x during the CT-BI Vacc-4x 2007/1 study. During the study a reduction in the viral load set-point (mean viral load at Week 48 and Week 52, or if Week 52 not reached, mean viral load of the last two measured values before restart of ART) was seen in the Vacc-4x group compared to placebo group. Further stimulation of the immune system by re-boosting with Vacc-4x could reduce the viral load set-point further.

Official Title
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Re-boosting of Subjects Previously Included in the CT BI-Vacc-4x 2007/1 Study. An Open, Multicenter, Immunogenicity, Follow-up Re-boosting Study With Vacc-4x in Subjects Infected With HIV-1 Who Have Maintained an Adequate Response to ART

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Biological: Vacc-4x


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed immunization regimen with Vacc-4x active and stopped ART (at Week 28) in the CT-BI Vacc-4x 2007/1 study. (No re-start of ART is required). Documented pre-study CD4 cell count ≥400x106/L. Documented pre-study viral load < 300 000copies/mL. Signed informed consent. Exclusion Criteria: Reported AIDS-defining illness within the previous year. Malignant disease. On chronic treatment with immune-suppressive therapy. Unacceptable values of the hematologic and clinical chemistry parameters, as judged by the Investigator, including creatinine values >1.5 x upper limit of normal (ULN), and AST, ALT and alkaline phosphatase (ALP) values >2.5 x ULN. Concurrent chronic active infection such as viral hepatitis B or C or tuberculosis. Pregnant or breastfeeding women. Women of childbearing potential not using reliable and adequate contraceptive methods (defined as: use of oral, implanted, injectable, mechanical or barrier products for the prevention of pregnancy; practicing abstinence; sterile) during the 5 weeks re-boosting period including the DTH and for 2 weeks after the DTH test, or sexually active male subjects with partners of child bearing potential unwilling to practice effective contraception during the 5 weeks re-boosting period including the DTH and for 12 weeks after the DTH-test. Current participation in other clinical therapeutic studies. Incapability of compliance to treatment protocol, in the opinion of the Investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 63 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Re-boosting with Vacc-4x<br>Intradermal Vacc-4x (1.2 mg) given with Leukine® (rhu-GM-CSF) (0.06 mg) at day 1 and day 15. | Biological: Vacc-4x<br>* Vacc-4x is a peptide-based HIV immunotherapy administered intradermally. Vacc-4x peptides are reconstituted in sterile water.<br>* Other names: Combination of Vacc-10, Vacc-11, Vacc-12 and Vacc-13;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vacc-4x Effect on Viral Load Set-point | Viral load (VL) set point in the present re-boost study was compared with VL set point in the 2007/1 study. | 37 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vacc-4x Effect on Immune Response Measured as CD4 Count | Effect of Re-boost with Vacc-4x on immune response obtained following immunization with Vacc-4x in Study CT-BI Vacc-4x 2007/1 | 36 weeks | 
| Vacc-4x Effect on Immune Response Measured as CD8 Count | Effect of Re-boost with Vacc-4x on immune response obtained following immunization with Vacc-4x in Study CT-BI Vacc-4x 2007/1 | 36 weeks | 
| Delayed Type Hypersensitivity Test (DTH), Positive Responses for Induration | The proportion of subjects who show Delayed Type Hypersensitivity (DTH) during the treatment phase. | 4 weeks | 
| Delayed Type Hypersensitivity Test (DTH), Positive Responses for Erythema | The proportion of subjects who show Delayed Type Hypersensitivity (DTH) during the treatment phase. | 4 Weeks | 
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | To evaluate the safety and tolerability of re-boosting with Vacc-4x by number of participants with Adverse Events | 37 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD4, Clinical trial, Human immunodeficiency virus-1 (HIV-1), HIV, Immunomodulary, Infection, Phase II, Re-boost, Vaccine, Vacc-4x