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

• ClinicalTrials.gov Identifier: NCT01712256
• Recruitment Status: Completed
• First Posted: October 23, 2012
• Results First Posted: March 6, 2017
• Last Update Posted: March 6, 2017
• Sponsor: Bionor Immuno AS
• Information provided by (Responsible Party): Bionor Immuno AS

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV-1 Infection	Biological: Vacc-4x	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: December 2012
• Actual Primary Completion Date: January 2014
• Actual Study Completion Date: January 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Biological: Vacc-4x; Vacc-4x is a peptide-based HIV immunotherapy administered intradermally. Vacc-4x peptides are reconstituted in sterile water.; Other Name: Combination of Vacc-10, Vacc-11, Vacc-12 and Vacc-13

Outcome Measures

Primary Outcome Measures :

1. Vacc-4x Effect on Viral Load Set-point [ Time Frame: 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 :

1. Vacc-4x Effect on Immune Response Measured as CD4 Count [ Time Frame: 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
2. Vacc-4x Effect on Immune Response Measured as CD8 Count [ Time Frame: 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
3. Delayed Type Hypersensitivity Test (DTH), Positive Responses for Induration [ Time Frame: 4 weeks ]
   The proportion of subjects who show Delayed Type Hypersensitivity (DTH) during the treatment phase.
4. Delayed Type Hypersensitivity Test (DTH), Positive Responses for Erythema [ Time Frame: 4 Weeks ]
   The proportion of subjects who show Delayed Type Hypersensitivity (DTH) during the treatment phase.
5. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 37 weeks ]
   To evaluate the safety and tolerability of re-boosting with Vacc-4x by number of participants with Adverse Events

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 63 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

UCLA CARE Center

Los Angeles, California, United States, 90035

UC Davis Medical Center

Sacramento, California, United States, 95817

Germany

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

Berlin, Germany, 12157

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

Bonn, Germany, 53127

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

Hamburg, Germany, 20099

Universitätsklinikum Hamburg Eppendorf

Hamburg, Germany, 20246

Italy

Istituto San Raffaele

Milano, Italy, 20127

Spain

Hospital Germans Trias i Pujol

Badalona, Spain, 08916

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

Barcelona, Spain, 08907

United Kingdom

Harrison Wing St Thomas' Hospital

London, United Kingdom, SE1 7EH

Sponsors and Collaborators

Bionor Immuno AS

Investigators

• Study Director: Vidar Wendel-Hansen, Dr. med; Bionor Pharma ASA, Kronprinsesse Märthas Plass 1, P.O. Box 1477 Vika, NO-0116 Oslo, Norway

More Information

Publications:

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.

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.

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Bionor Immuno AS
• ClinicalTrials.gov Identifier: NCT01712256
• Other Study ID Numbers: CT-BI Vacc-4x 2012/1
• First Posted: October 23, 2012
• Results First Posted: March 6, 2017
• Last Update Posted: March 6, 2017
• Last Verified: January 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Participants have not provided informed consent for their anonymized individual data to be made available beyond that described in the patient information sheet.

Keywords provided by Bionor Immuno AS:

CD4; Clinical trial; Human immunodeficiency virus-1 (HIV-1); HIV; Immunomodulary; Infection; Phase II; Re-boost; Vaccine; Vacc-4x

Additional relevant MeSH terms:

Infections