Re-boosting of HIV-1 Infected Subjects With Vacc-4x (Re-boost)
Primary Purpose
HIV-1 Infection
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Vacc-4x
Sponsored by

About this trial
This is an interventional treatment trial for HIV-1 Infection focused on measuring CD4, Clinical trial, Human immunodeficiency virus-1 (HIV-1), HIV, Immunomodulary, Infection, Phase II, Re-boost, Vaccine, Vacc-4x
Eligibility Criteria
Inclusion Criteria:
- 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).
- Documented pre-study CD4 cell count ≥400x106/L.
- Documented pre-study viral load < 300 000copies/mL.
- Signed informed consent.
Exclusion Criteria:
- Reported AIDS-defining illness within the previous year.
- Malignant disease.
- On chronic treatment with immune-suppressive therapy.
- 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.
- Concurrent chronic active infection such as viral hepatitis B or C or tuberculosis.
- Pregnant or breastfeeding women.
- 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.
- Current participation in other clinical therapeutic studies.
- Incapability of compliance to treatment protocol, in the opinion of the Investigator.
Sites / Locations
- UCLA CARE Center
- UC Davis Medical Center
- EIPMED - Gesellschaft fűr epidemiologische und klinische Forschung in der Medizin mbH Rubensstrasse 125
- Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I; Immunologische Ambulanz, Siegmund-Freud-Str. 25
- ifi - Studien und Projekte GmbH, an der Asklepios-Klinik St. George
- Universitätsklinikum Hamburg Eppendorf
- Istituto San Raffaele
- Hospital Germans Trias i Pujol
- Unidad de VIH, Hospital de Bellvitge, Calle Feixa Llarga s/n, Hospitalet de Llobregat.
- Harrison Wing St Thomas' Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Re-boosting with Vacc-4x
Arm Description
Intradermal Vacc-4x (1.2 mg) given with Leukine® (rhu-GM-CSF) (0.06 mg) at day 1 and day 15.
Outcomes
Primary Outcome Measures
Vacc-4x Effect on Viral Load Set-point
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
Vacc-4x Effect on Immune Response Measured as CD4 Count
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
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
The proportion of subjects who show Delayed Type Hypersensitivity (DTH) during the treatment phase.
Delayed Type Hypersensitivity Test (DTH), Positive Responses for Erythema
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
To evaluate the safety and tolerability of re-boosting with Vacc-4x by number of participants with Adverse Events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01712256
Brief Title
Re-boosting of HIV-1 Infected Subjects With Vacc-4x
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
December 2012 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
January 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bionor Immuno AS
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV-1 Infection
Keywords
CD4, Clinical trial, Human immunodeficiency virus-1 (HIV-1), HIV, Immunomodulary, Infection, Phase II, Re-boost, Vaccine, Vacc-4x
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Re-boosting with Vacc-4x
Arm Type
Experimental
Arm Description
Intradermal Vacc-4x (1.2 mg) given with Leukine® (rhu-GM-CSF) (0.06 mg) at day 1 and day 15.
Intervention Type
Biological
Intervention Name(s)
Vacc-4x
Other Intervention Name(s)
Combination of Vacc-10, Vacc-11, Vacc-12 and Vacc-13
Intervention Description
Vacc-4x is a peptide-based HIV immunotherapy administered intradermally. Vacc-4x peptides are reconstituted in sterile water.
Primary Outcome Measure Information:
Title
Vacc-4x Effect on Viral Load Set-point
Description
Viral load (VL) set point in the present re-boost study was compared with VL set point in the 2007/1 study.
Time Frame
37 weeks
Secondary Outcome Measure Information:
Title
Vacc-4x Effect on Immune Response Measured as CD4 Count
Description
Effect of Re-boost with Vacc-4x on immune response obtained following immunization with Vacc-4x in Study CT-BI Vacc-4x 2007/1
Time Frame
36 weeks
Title
Vacc-4x Effect on Immune Response Measured as CD8 Count
Description
Effect of Re-boost with Vacc-4x on immune response obtained following immunization with Vacc-4x in Study CT-BI Vacc-4x 2007/1
Time Frame
36 weeks
Title
Delayed Type Hypersensitivity Test (DTH), Positive Responses for Induration
Description
The proportion of subjects who show Delayed Type Hypersensitivity (DTH) during the treatment phase.
Time Frame
4 weeks
Title
Delayed Type Hypersensitivity Test (DTH), Positive Responses for Erythema
Description
The proportion of subjects who show Delayed Type Hypersensitivity (DTH) during the treatment phase.
Time Frame
4 Weeks
Title
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Description
To evaluate the safety and tolerability of re-boosting with Vacc-4x by number of participants with Adverse Events
Time Frame
37 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
63 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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).
Documented pre-study CD4 cell count ≥400x106/L.
Documented pre-study viral load < 300 000copies/mL.
Signed informed consent.
Exclusion Criteria:
Reported AIDS-defining illness within the previous year.
Malignant disease.
On chronic treatment with immune-suppressive therapy.
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.
Concurrent chronic active infection such as viral hepatitis B or C or tuberculosis.
Pregnant or breastfeeding women.
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.
Current participation in other clinical therapeutic studies.
Incapability of compliance to treatment protocol, in the opinion of the Investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vidar Wendel-Hansen, Dr. med
Organizational Affiliation
Bionor Pharma ASA, Kronprinsesse Märthas Plass 1, P.O. Box 1477 Vika, NO-0116 Oslo, Norway
Official's Role
Study Director
Facility Information:
Facility Name
UCLA CARE Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90035
Country
United States
Facility Name
UC Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
EIPMED - Gesellschaft fűr epidemiologische und klinische Forschung in der Medizin mbH Rubensstrasse 125
City
Berlin
ZIP/Postal Code
12157
Country
Germany
Facility Name
Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I; Immunologische Ambulanz, Siegmund-Freud-Str. 25
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
ifi - Studien und Projekte GmbH, an der Asklepios-Klinik St. George
City
Hamburg
ZIP/Postal Code
20099
Country
Germany
Facility Name
Universitätsklinikum Hamburg Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Istituto San Raffaele
City
Milano
ZIP/Postal Code
20127
Country
Italy
Facility Name
Hospital Germans Trias i Pujol
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Unidad de VIH, Hospital de Bellvitge, Calle Feixa Llarga s/n, Hospitalet de Llobregat.
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Harrison Wing St Thomas' Hospital
City
London
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing 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.
Citations:
PubMed Identifier
22339677
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.
Results Reference
background
PubMed Identifier
22339485
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.
Results Reference
background
PubMed Identifier
20721838
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.
Results Reference
background
PubMed Identifier
16470131
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.
Results Reference
background
PubMed Identifier
30699178
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.
Results Reference
derived
Learn more about this trial
Re-boosting of HIV-1 Infected Subjects With Vacc-4x
We'll reach out to this number within 24 hrs