Safety and Immunogenicity Study of GX-70 in TB Patient

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety, tolerability, and immunogenicity in patients with pulmonary tuberculosis of an investigational DNA vaccine being developed for the prevention of relapse of tuberculosis.

Detailed Description
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Tuberculosis still matters in domestic as well as global public health. According to WHO, 8,700,000 cases of tuberculosis occured in 2011, and 1,400,000 of them resulted dead. Tuberculosis patients with the cavity and positive on AFB show high rate of relapse and treatment failure. Those with high risk of relapse and treatment failure may need more effective treatment before acquiring resistance and infecting others. GX-70, which consists of the four-antigen plasmids from MTB together with recombinant Flt3 ligand is an investigational DNA vaccine designed to prevent relapse or treatment failure. The purpose of this study is to assess safety of GX-70, in pulmonary TB patients with high risk factors for treatment failure or relapse.

Official Title
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A Open-label, Dose Escalation, Phase 1 Clinical Trial to Evaluate the Tolerability, Safety and Immunogenicity of GX-70, a DNA-based Therapeutic Vaccine, Administered Intramuscularly by Electroporation (EP) in Patients With Pulmonary Tuberculosis Who Have High Risk Factors for Relapse or Treatment Failure

Conditions
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Pulmonary Tuberculoses, High Risk Factors for Relapse, Treatment Failure

Intervention / Treatment
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* Drug: GX-70 by electroporation
* Drug: GX-70 by electroporation
* Drug: GX-70 by electroporation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who voluntarily consented, after listening enough explanation for this study and investigational product. Adults between 19 and 65 years. TB patients without a history of TB diagnosis, who show positive on both AFB smear and TB-PCR TB patients who satisfy following conditions: cavity spotted from chest imaging before TB therapy, positive on AFB smear 2 months after TB therapy. Exclusion Criteria: At 2 months after therapy started, AFB smear shows 1+ or higher, but TB PCR shows NTM positive. If positive on AFB smear is resulted from dead MTB Serious TB such as tuberculous encephalomeningitis Patients with serious pulmonary symptom except TB Patients show poor vital sign considered to be difficult to participate Patients with heart, renal, or liver failure Patients with infection, ulcer, edema, tattoo, scar, wound and other conditions in skin around 3cm of deltoid muscle that result inappropriate to inject through electroporation. When thickness of skin around deltoid muscle which is to be injected exceeds 40mm Patients with QTc prolongation on 12-lead ECG Patients with a cardiac device (such as a pacemaker) Patients that the researchers do not think fit into the group, including patients failed in compliance assessment

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 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: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Dose level 1 : GX-70 0.26mg Dose level 2 : GX-70 1mg Dose level 3 : GX-70 4mg
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose level 1 (GX-70 0.26mg)<br>Administrating GX-70 0.26mg | Drug: GX-70 by electroporation<br>* Gx-70 0.26mg will be administered by electroporation in the deltoid muscles every 4 weeks 5 times<br>|
| Experimental: Dose level 2 (GX-70 1mg)<br>Administrating GX-70 1mg | Drug: GX-70 by electroporation<br>* Gx-70 1mg will be administered by electroporation in the deltoid muscles every 4 weeks 5 times<br>|
| Experimental: Dose level 3 (GX-70 4mg)<br>Administrating GX-70 4mg | Drug: GX-70 by electroporation<br>* Gx-70 4mg will be administered by electroporation in the deltoid muscles every 4 weeks 5 times<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD (Maximum Tolerant Dose) |  | Every 4 weeks up to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IFN-γ (SFC/106 cells) | IFN-γ response stimulated by TB antigens | Every 8 weeks up to 24 weeks | 
| Flt3L concentration (pg/ml) | Every 8 weeks up to 24 weeks | Every 8 weeks up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis, DNA vaccine, Electroporation, GX-70