High Risk Factors for Relapse, Pulmonary Tuberculoses, Treatment Failure
Conditions
Keywords
Tuberculosis, DNA vaccine, Electroporation, GX-70
Brief summary
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
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.
Interventions
DRUGGX-70 by electroporation
Gx-70 0.26mg will be administered by electroporation in the deltoid muscles every 4 weeks 5 times
Sponsors
Yonsei University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
1. Dose level 1 : GX-70 0.26mg 2. Dose level 2 : GX-70 1mg 3. Dose level 3 : GX-70 4mg
Eligibility
Sex/Gender
ALL
Age
19 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects who voluntarily consented, after listening enough explanation for this study and investigational product. 2. Adults between 19 and 65 years. 3. TB patients without a history of TB diagnosis, who show positive on both AFB smear and TB-PCR 4. 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
1. At 2 months after therapy started, AFB smear shows 1+ or higher, but TB PCR shows NTM positive. 2. If positive on AFB smear is resulted from dead MTB 3. Serious TB such as tuberculous encephalomeningitis 4. Patients with serious pulmonary symptom except TB 5. Patients show poor vital sign considered to be difficult to participate 6. Patients with heart, renal, or liver failure 7. 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. 8. When thickness of skin around deltoid muscle which is to be injected exceeds 40mm 9. Patients with QTc prolongation on 12-lead ECG 10. Patients with a cardiac device (such as a pacemaker) 11. Patients that the researchers do not think fit into the group, including patients failed in compliance assessment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| MTD (Maximum Tolerant Dose) | Every 4 weeks up to 16 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| IFN-γ (SFC/106 cells) | Every 8 weeks up to 24 weeks | IFN-γ response stimulated by TB antigens |
| Flt3L concentration (pg/ml) | Every 8 weeks up to 24 weeks | Every 8 weeks up to 24 weeks |
Outcome results
None listed