Safety and Immunogenicity Study of GX-70 in TB Patient

Pulmonary Tuberculoses Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03159975
• Other study ID #: 4-2016-1144
• Status: Withdrawn
• Phase: Phase 1
• Start date: March 2018
• Est. completion date: August 2018

Study information

• Verified date: January 2019
• Source: Yonsei University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 2018
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• High Risk Factors for Relapse
• Pulmonary Tuberculoses
• Recurrence
• Treatment Failure
• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

Drug:
• GX-70 by electroporation
Gx-70 0.26mg will be administered by electroporation in the deltoid muscles every 4 weeks 5 times
• GX-70 by electroporation
Gx-70 1mg will be administered by electroporation in the deltoid muscles every 4 weeks 5 times
• GX-70 by electroporation
Gx-70 4mg will be administered by electroporation in the deltoid muscles every 4 weeks 5 times

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

References & Publications (3)

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. — View 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. Epub 2004 Sep 16. — View Citation

Flynn JL, Chan J. Tuberculosis: latency and reactivation. Infect Immun. 2001 Jul;69(7):4195-201. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MTD (Maximum Tolerant Dose)		Every 4 weeks up to 16 weeks
Secondary	IFN-? (SFC/106 cells)	IFN-? response stimulated by TB antigens	Every 8 weeks up to 24 weeks
Secondary	Flt3L concentration (pg/ml)	Every 8 weeks up to 24 weeks	Every 8 weeks up to 24 weeks

External Links

•   World Health Organization. Global tuberculosis report 2012.