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

HIV-1 Infection Clinical Trial

— Re-boost  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01712256
• Other study ID #: CT-BI Vacc-4x 2012/1
• Status: Completed
• Phase: Phase 2
• First received: October 16, 2012
• Last updated: January 13, 2014
• Start date: December 2012
• Est. completion date: January 2014

Study information

• Verified date: January 2014
• Source: Bionor Immuno AS
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics CommitteeGermany: Paul-Ehrlich-InstitutGermany: Ethics CommissionItaly: Ethics CommitteeSpain: Spanish Agency of MedicinesSpain: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 63 Years

Eligibility

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

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

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Biological:
• Vacc-4x
Two re-boost immunisations with adjuvant and vacc-4x, one at week 1 and one at week 3.

Locations

Country	Name	City	State
Germany	EIPMED - Gesellschaft fur epidemiologische und klinische Forschung in der Medizin mbH Rubensstrasse 125	Berlin
Germany	Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I; Immunologische Ambulanz, Siegmund-Freud-Str. 25	Bonn
Germany	ifi - Studien und Projekte GmbH, an der Asklepios-Klinik St. George	Hamburg
Germany	Universitätsklinikum Hamburg Eppendorf	Hamburg
Italy	Istituto San Raffaele	Milano
Spain	Hospital Germans Trias i Pujol	Badalona
Spain	Unidad de VIH, Hospital de Bellvitge, Calle Feixa Llarga s/n, Hospitalet de Llobregat.	Barcelona
United Kingdom	Harrison Wing St Thomas' Hospital	London
United States	UCLA CARE Center	Los Angeles	California
United States	UC Davis Medical Center	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
Bionor Immuno AS

Countries where clinical trial is conducted

United States,  Germany,  Italy,  Spain,  United Kingdom, 

References & Publications (4)

Jones T. Vacc-4x, a therapeutic vaccine comprised of four engineered peptides for the potential treatment of HIV infection. Curr Opin Investig Drugs. 2010 Aug;11(8):964-70. — View Citation

Kran AM, Sommerfelt MA, Baksaas I, Sørensen B, Kvale D. Delayed-type hypersensitivity responses to HIV Gag p24 relate to clinical outcome after peptide-based therapeutic immunization for chronic HIV infection. APMIS. 2012 Mar;120(3):204-9. doi: 10.1111/j.1600-0463.2011.02843.x. Epub 2011 Nov 27. — View Citation

Kran AM, Sørensen B, Sommerfelt MA, Nyhus J, Baksaas I, Kvale D. Long-term HIV-specific responses and delayed resumption of antiretroviral therapy after peptide immunization targeting dendritic cells. AIDS. 2006 Feb 28;20(4):627-30. — View Citation

Lind A, Sommerfelt M, Holmberg JO, Baksaas I, Sørensen B, Kvale D. Intradermal vaccination of HIV-infected patients with short HIV Gag p24-like peptides induces CD4 + and CD8 + T cell responses lasting more than seven years. Scand J Infect Dis. 2012 Aug;44(8):566-72. doi: 10.3109/00365548.2011.653581. Epub 2012 Feb 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vacc-4x effect on viral load set-point	The effect of Re-boost with Vacc-4x on the viral load set-point obtained following immunization with Vacc-4x in Study CT-BI Vacc-4x 2007/1 by measuring viral load before and after reboosting.	37 weeks	Yes
Primary	Vacc-4x effect on immune response	Effect of Re-boost with Vacc-4x on immune response obtained following immunization with Vacc-4x in Study CT-BI Vacc-4x 2007/1	37 weeks	No
Secondary	CD4 counts	Effect of a re-boost with Vacc-4x on CD4 counts	37 weeks	Yes
Secondary	Delayed Type Hypersensitivity test(DTH)	In vivo immunogenicity of Vacc-4x by delayed-type hypersensitivity (DTH) and to compare the DTH response to the DTH response observed in the initial study; CT-BI Vacc-4x 2007/1	37 weeks	No
Secondary	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	Yes
Secondary	CD8 counts	Effect of a re-boost with Vacc-4x on CD8 counts	37 weeks	No