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

Phase 2

Completed

• Conditions: HIV-1 Infection
• Interventions: Biological: Vacc-4x

• Registration Number: NCT01712256
• Lead Sponsor: Bionor Immuno AS

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2012-10-16
• Study First Submitted QC: 2012-10-19
• Study First Posted: 2012-10-23
• Study Start: 2012-12
• Primary Completion: 2014-01
• Study Completion: 2014-01
• Status Verified: 2017-01
• Results First Submitted: 2017-01-11
• Results First Submitted QC: 2017-01-11
• Last Update Submitted: 2017-01-11
• Results First Posted: 2017-03-06
• Last Update Posted: 2017-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

Inclusion Criteria

1. 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).
2. Documented pre-study CD4 cell count ≥400x106/L.
3. Documented pre-study viral load < 300 000copies/mL.
4. Signed informed consent.

Exclusion Criteria

1. Reported AIDS-defining illness within the previous year.
2. Malignant disease.
3. On chronic treatment with immune-suppressive therapy.
4. 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.
5. Concurrent chronic active infection such as viral hepatitis B or C or tuberculosis.
6. Pregnant or breastfeeding women.
7. 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.
8. Current participation in other clinical therapeutic studies.
9. Incapability of compliance to treatment protocol, in the opinion of the Investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Re-boosting with Vacc-4x	Vacc-4x	Intradermal Vacc-4x (1.2 mg) given with Leukine® (rhu-GM-CSF) (0.06 mg) at day 1 and day 15.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (10)

UC Davis Medical Center; 🇺🇸 Sacramento, California, United States

EIPMED - Gesellschaft fűr epidemiologische und klinische Forschung in der Medizin mbH Rubensstrasse 125; 🇩🇪 Berlin, Germany

ifi - Studien und Projekte GmbH, an der Asklepios-Klinik St. George; 🇩🇪 Hamburg, Germany

Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I; Immunologische Ambulanz, Siegmund-Freud-Str. 25; 🇩🇪 Bonn, Germany

Istituto San Raffaele; 🇮🇹 Milano, Italy

Hospital Germans Trias i Pujol; 🇪🇸 Badalona, Spain

Unidad de VIH, Hospital de Bellvitge, Calle Feixa Llarga s/n, Hospitalet de Llobregat.; 🇪🇸 Barcelona, Spain

Universitätsklinikum Hamburg Eppendorf; 🇩🇪 Hamburg, Germany

Harrison Wing St Thomas' Hospital; 🇬🇧 London, United Kingdom

UCLA CARE Center; 🇺🇸 Los Angeles, California, United States