Clinical trial NCT01712256: Re-boosting of HIV-1 Infected Subjects With Vacc-4x
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1 Infection
Keywords: CD4
Clinical trial
Human immunodeficiency virus-1 (HIV-1)
HIV
Immunomodulary
Infection
Phase II
Re-boost
Vaccine
Vacc-4x
Lead sponsor: Bionor Immuno AS
Sponsor class: INDUSTRY
First posted: 2012-10-23
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 63
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Vacc-4x Effect on Viral Load Set-point
timeFrame: 37 weeks
Secondary outcomes:
measure: Vacc-4x Effect on Immune Response Measured as CD4 Count
timeFrame: 36 weeks
measure: Vacc-4x Effect on Immune Response Measured as CD8 Count
timeFrame: 36 weeks
measure: Delayed Type Hypersensitivity Test (DTH), Positive Responses for Induration
timeFrame: 4 weeks
measure: Delayed Type Hypersensitivity Test (DTH), Positive Responses for Erythema
timeFrame: 4 Weeks
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: 37 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA CARE Center
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Berlin
country: Germany
facility: EIPMED - Gesellschaft fűr epidemiologische und klinische Forschung in der Medizin mbH Rubensstrasse 125
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I; Immunologische Ambulanz, Siegmund-Freud-Str. 25
city: Hamburg
country: Germany
facility: ifi - Studien und Projekte GmbH, an der Asklepios-Klinik St. George
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf
city: Milano
country: Italy
facility: Istituto San Raffaele
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Unidad de VIH, Hospital de Bellvitge, Calle Feixa Llarga s/n, Hospitalet de Llobregat.
city: London
country: United Kingdom
facility: Harrison Wing St Thomas' Hospital
Study officials:
affiliation: Bionor Pharma ASA, Kronprinsesse Märthas Plass 1, P.O. Box 1477 Vika, NO-0116 Oslo, Norway
name: Vidar Wendel-Hansen, Dr. med
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.