Safety of Recombinant Fusion Protein ESAT6-CFP10 as a Skin Test Reagent for Tuberculosis Diagnosis: an Open-Label, Randomized, Single-Center Phase I Clinical Trial

Abstract

This trial was conducted to explore the safety of recombinant fusion protein ESAT6-CFP10 as a skin test reagent for the diagnosis of Mycobacterium tuberculosis infection. Twenty-four healthy adult volunteers were recruited and randomized into four groups (groups A to D) to study four increasing doses of ESAT6-CFP10. All subjects in each dose group received an intradermal injection of reagent (0.1 ml) via the Mantoux technique. Then, the vital signs of all subjects were monitored, and skin reactions around injection sites and adverse events were recorded at different detection time points after the skin test. No serious adverse events were observed in this study. A total of 3 subjects had unexpected events. One subject in group A developed subcutaneous hemorrhage 24 h after the skin test, one subject in group B was found with red spots 15 min after the skin test, and another subject in group A showed abnormity during a chest X-ray after the skin test without affecting her health. One of three adverse events (red spots) was probably related to the recombinant ESAT6-CFP10 reagent. A single dose of 1, 5, 10, or 20 μg/ml of recombinant ESAT6-CFP10 as a skin test reagent for M. tuberculosis infection diagnosis is well tolerated and safe in China. (This study has been registered at ClinicalTrials.gov under registration no. NCT01999231.).

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Figures

FIG 1

Flow diagram of study design. All subjects in this trial received an intradermal injection with a single dose of ESAT6-CFP10, with a total volume of 0.1 ml. The increasing doses of the reagent were 1 μg/ml (group A), 5 μg/ml (group B), 10 μg/ml (group C), and 20 μg/ml (group D).

FIG 2

Mild skin reactions in one subject (no. 6) in group A (subjects received 1 μg/ml of ESAT6-CFP10), who developed a 2- by 2-mm subcutaneous hemorrhage at the injection site 24 h after the skin test, which flattened at 48 and 72 h and subsided at 96 h after the skin test.

FIG 3

Mild skin reactions in one subject (no. 2) in group B (subjects received 5 μg/ml of ESAT6-CFP10), who was observed with red spots scattered within an area of 32 by 25 mm at the injection site 15 min after the skin test. These red spots disappeared on the next day after the skin test.