Clinical trial NCT03159975: Safety and Immunogenicity Study of GX-70 in TB Patient
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Pulmonary Tuberculoses
High Risk Factors for Relapse
Treatment Failure
Keywords: Tuberculosis
DNA vaccine
Electroporation
GX-70
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2017-05-19
Enrollment: 0
Sex: ALL
Minimum age (years): 19
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
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
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: MTD (Maximum Tolerant Dose)
timeFrame: Every 4 weeks up to 16 weeks
Secondary outcomes:
measure: IFN-γ (SFC/106 cells)
timeFrame: Every 8 weeks up to 24 weeks
measure: Flt3L concentration (pg/ml)
timeFrame: Every 8 weeks up to 24 weeks
Other outcomes:
Locations:
Study officials:
References:
citation: Flynn JL, Chan J. Tuberculosis: latency and reactivation. Infect Immun. 2001 Jul;69(7):4195-201. doi: 10.1128/IAI.69.7.4195-4201.2001. No abstract available.
citation: Chang KC, Leung CC, Yew WW, Ho SC, Tam CM. A nested case-control study on treatment-related risk factors for early relapse of tuberculosis. Am J Respir Crit Care Med. 2004 Nov 15;170(10):1124-30. doi: 10.1164/rccm.200407-905OC. Epub 2004 Sep 16.
citation: Ahn SS, Jeon BY, Kim KS, Kwack JY, Lee EG, Park KS, Sung YC, Cho SN. Mtb32 is a promising tuberculosis antigen for DNA vaccination in pre- and post-exposure mouse models. Gene Ther. 2012 May;19(5):570-5. doi: 10.1038/gt.2011.140. Epub 2011 Sep 29.