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

NCT ID: NCT01712256

Last Updated: 2017-03-06

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

33 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-12-31

Study Completion Date

2014-01-31

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.

Conditions

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HIV-1 Infection

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Re-boosting with Vacc-4x

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

Group Type EXPERIMENTAL

Vacc-4x

Intervention Type BIOLOGICAL

Vacc-4x is a peptide-based HIV immunotherapy administered intradermally. Vacc-4x peptides are reconstituted in sterile water.

Interventions

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Vacc-4x

Vacc-4x is a peptide-based HIV immunotherapy administered intradermally. Vacc-4x peptides are reconstituted in sterile water.

Intervention Type BIOLOGICAL

Other Intervention Names

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Combination of Vacc-10, Vacc-11, Vacc-12 and Vacc-13

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

63 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bionor Immuno AS

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Vidar Wendel-Hansen, Dr. med

Role: STUDY_DIRECTOR

Bionor Pharma ASA, Kronprinsesse Märthas Plass 1, P.O. Box 1477 Vika, NO-0116 Oslo, Norway

Locations

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UCLA CARE Center

Los Angeles, California, United States

Site Status

UC Davis Medical Center

Sacramento, California, United States

Site Status

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

Bonn, Bonn, Germany

Site Status

ifi - Studien und Projekte GmbH, an der Asklepios-Klinik St. George

Hamburg, City state of Hamburg, Germany

Site Status

EIPMED - Gesellschaft fűr epidemiologische und klinische Forschung in der Medizin mbH Rubensstrasse 125

Berlin, State of Berlin, Germany

Site Status

Universitätsklinikum Hamburg Eppendorf

Hamburg, , Germany

Site Status

Istituto San Raffaele

Milan, Milano, Italy

Site Status

Hospital Germans Trias i Pujol

Badalona, , Spain

Site Status

Unidad de VIH, Hospital de Bellvitge, Calle Feixa Llarga s/n, Hospitalet de Llobregat.

Barcelona, , Spain

Site Status

Harrison Wing St Thomas' Hospital

London, London, United Kingdom

Site Status

Countries

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United States Germany Italy Spain United Kingdom

References

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Kran AM, Sommerfelt MA, Baksaas I, Sorensen 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.

Reference Type BACKGROUND
PMID: 22339677 (View on PubMed)

Lind A, Sommerfelt M, Holmberg JO, Baksaas I, Sorensen 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.

Reference Type BACKGROUND
PMID: 22339485 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20721838 (View on PubMed)

Kran AM, Sorensen 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. doi: 10.1097/01.aids.0000210620.75707.ac.

Reference Type BACKGROUND
PMID: 16470131 (View on PubMed)

Rockstroh JK, Asmuth D, Pantaleo G, Clotet B, Podzamczer D, van Lunzen J, Arasteh K, Mitsuyasu R, Peters B, Silvia N, Jolliffe D, Okvist M, Krogsgaard K, Sommerfelt MA. Re-boost immunizations with the peptide-based therapeutic HIV vaccine, Vacc-4x, restores geometric mean viral load set-point during treatment interruption. PLoS One. 2019 Jan 30;14(1):e0210965. doi: 10.1371/journal.pone.0210965. eCollection 2019.

Reference Type DERIVED
PMID: 30699178 (View on PubMed)

Other Identifiers

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CT-BI Vacc-4x 2012/1

Identifier Type: -

Identifier Source: org_study_id

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