Gene Therapy With GX-12 in Combination With HAART for the HIV-1 Infected Patients

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety of GX-12 gene therapy combined with HAART in the HIV-1 infected patients and to investigate the efficacy with the value of plasma viral load and with CD4 counts and HIV-1 specific IFN-gamma expressed T-lymphocytes

Detailed Description
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Currently, management of HIV infection and AIDS is mainly done by antiviral chemotherapy which inhibits reverse transcriptase or proteolytic enzyme. The HAART (highly active antiretroviral therapy) has indeed succeeded extraordinary in decrease of the mortality and in increase of the life expediency of AIDS patients. However, there have been some significant limitations of them (for example, treatment fatigues, the side effects, the emergency of resistant, high medical costs, etc.). Recently, there has been a number of bioresearch for immunotherapy to overcome these limitations of current medications. GX-12 is a genetic using a naked DNA with human IL-12 mutant as immune adjuvant. GX-12 is designed to vaccinate the individuals with HIV antigens, which is to result in enhancing the HIV specific immunity and to expand broadly the immune responses nonspecifically. In this study, the safety and efficacy of GX-12 will be investigated.

Official Title
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Phase I Study for Assessment of Safety of Gene Therapy With GX-12 in Combination With HAART for the HIV-1 Infected Patients

Conditions
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HIV Infections

Intervention / Treatment
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* Genetic: GX-12
* Drug: HAART


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 18 and 50 years HIV-1 type B infected but asymptomatic patient Patient who has received HAART less than 6 months according to the standard management guidelines and reached to aviremia Patient with appropriate immunity (i.e., CD4 counts>=400cells/ul and SI>3 by CD4+ T-cell proliferation in vitro assay) Patient with negative HBV and HCV Woman who is not childbearing or who has used any contraceptive at least for 3 months before study entry Patients given a written consent Exclusion Criteria: Patient who has received other investigational drug or who participated into other study within 30 days before this study Patient who had an experience of hypersensitivity to same drug (for example: a plasmid DNA, etc) Patient who has received an immunosuppressant Patient who has received other HIV vaccine Patient who has received other interleukin(s) Patient who experienced an opportunistic infection defined as AIDS before this study Patient with any severe recurrent diarrhea or vomiting Patient with clinically significant acute or chronic liver dysfunction, kidney dysfunction, hematological disorder, endocrine disorder, immune disorder, heart disease, infection, etc. Patient with malignant tumor(s) Patient with alcohol or drug abuse Patient of potential harm due to drug interactions by HAART Woman of pregnancy (positive pregnancy test) or beast feeding Patient who is not appropriate at investigator's discretion, not specified in above

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>GX-12 combined with HAART | Genetic: GX-12<br>* a mixed plasma DNA (HIV-1 antigen genes and human IL-12 mutant) 4, 8, 16mg, i.m., once every other weeks for 22 weeks (total 12 times)<br>Drug: HAART<br>* Highly active antiretroviral therapy; Discontinuation at 24 weeks; NB: The patients should be treated with 2 NRTIs+1 NNRTI or 2 NRTIs + 1 PI, according to the guidelines published by DHHS in the USA.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: adverse events and laboratory abnormalities |  | 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary efficacy endpoint: plasma viral load Secondary efficacy endpoint: CD4 counts and HIV-1 Antigen specific IFN-gamma expressed T-lymphocytes |  | 24, 28, 32 and 36 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gene Therapy, GX-12, HIV-1, Interleukin, AIDS, HIV-1 type B infection, Treatment Naive