Immunogenicity Study of Vacc-4x Versus Placebo in Patients Infected With HIV

Study Overview
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Brief Summary
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Current management of HIV infection includes anti-retroviral therapy (ART). ART cannot cure the infection, making it a life-long treatment that requires sustained patient compliance and imposes significant individual and societal financial burdens on healthcare services. Furthermore, ART side effects often require medication that increases the inconveniences and financial burdens of HIV management. Of further concern is the emergence of viruses resistant to ART that can result in treatment failure. ART-free periods could provide substantial benefit. Vacc-4x is a peptide-based HIV immunotherapy that is proposed for prolongation of ART-free periods. The purpose of this study is to determine whether Vacc-4x immunotherapy can give safe ART-free period.

Detailed Description
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Current management of HIV infection includes anti-retroviral therapy (ART). ART cannot cure the infection, making it a life-long treatment that requires sustained patient compliance and imposes significant individual and societal financial burdens on healthcare services. Furthermore,ART side effects often require medication that increases the inconveniences and financial burdens of HIV management. Of further concern is the emergence of viruses resistant to ART that can result in treatment failure. ART-free periods could provide substantial benefit. Vacc-4x is a peptide-based HIV immunotherapy that is proposed for prolongation of ART-free periods. The purpose of this study is to determine whether Vacc-4x immunotherapy can give safe ART-free period.

Official Title
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A Phase II, Randomized, Double-blind, Multicenter, Immunogenicity Study of Vacc-4x Versus Placebo in Patients Infected With HIV-1 Who Have Maintained an Adequate Response to ART

Conditions
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HIV I Infection

Intervention / Treatment
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* Drug: Vacc-4x
* Drug: Sterile water


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-55 HIV positive at least one year Clinically stable on ART for at least six months Documented viral load less than 50 copies/mL for the last six months Documented prestudy CD4 cell count equal or more than 400x10exp6/L Nadir CD4 cell count equal or more than 200x10exp6/L Signed informed consent Exclusion Criteria: Reported pre-study AIDS-defining illness within the previous year Malignant disease On chronic treatment with immuno-suppressive therapy Unacceptable values of hematology and clinical chemistry parameters Current chronic infection such as HCV and HBV or active tuberculosis Pregnant or breastfeeding women Not using safe contraceptive methods Participation in other clinical trial Incapability of compliance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vacc-4x<br>Vacc-4x reconstituted in sterile water (0.1 mL) at a dose of 1.2mg per intradermal administration. Participants are given a total of 6 immunizations over 18 weeks (weeks 1, 2, 3, 4, 16, 18). Recombinant human granulocyte macrophage colony stimulating factor (rhuGM-CSF) Leukine (0.06mg in 0.1 mL) administered intradermally is used as a local adjuvant. | Drug: Vacc-4x<br>* Vacc-4x is a peptide-based HIV immunotherapy administered intradermally. Vacc-4x peptides are reconstituted in sterile water.<br>* Other names: Combination of Vacc-10, Vacc-11, Vacc-12 and Vacc-13.;|
| Placebo Comparator: Placebo<br>Placebo injections consisting of sterile water (0.1 mL) in place of Vacc-4x. Placebo injections consisting of sterile water (0.1 mL) in place of Leukine. | Drug: Sterile water<br>* Sterile water is used in place of Vacc-4x and in place of Leukine<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Who Require Resumption of ART Between the Interruption of ART at Week 28 and End of Study at Week 52. |  | From Week 28 to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Any Treatment Emergent Adverse Event, Related Treatment Emergent Adverse Events and Deaths | Brief summary of treatment emergent adverse events or related treatment emergent events and deaths. The intensity of adverse events was described according to the Division of AIDS table for grading severity of adult and pediatric adverse events, 2004. | Up to week 52 | 
| Immunogenicity | Immunogenicity of Vacc-4x evaluated by DTH (Delayed-type Hypersensitivity) reaction. The number of participants showing induration and/or erythema | Week 1, week 18 and week 52 | 
| Effect of Vacc-4x on CD8 Counts | CD8 Count Over Time for subjects who stopped ART at Week 28 and remained off ART until Week 52 | Weeks 6,18,24,28,32,36,40,44,48,52. | 
| Time to Restart of ART for Vacc-4x Subjects Versus Placebo | Kaplan-Meier Estimate of Time to restart ART (from time coming off ART) | Between Week 28 to Week 52 | 
| Effects on Vacc-4x on HIV-1 RNA |  | Weeks 24,28,32,36,40,44,48,52. |