Safety and Diagnostic Performance of Recombinant Fusion Protein ESAT6-CPF10 Skin Test in A Large Population: A Phase 4 Clinical Trial.
Junji Chen, Luqing Zhao, Xiang Zhou, Yi Mo, Lanting Kong, Fangli Ma, Liangyong Wu, Dingjin Huang, et al. (10 authors)
The Journal of infectious diseases · 2025-10
Abstract
BACKGROUND: This study aimed to evaluate the safety and diagnostic performance of recombinant fusion protein early secretory antigenic target protein 6-culture filtrate protein 10 (EC) in a community-based population aged ≥6 months.
METHODS: We conducted a 2-stage trial in a community-based population. The first stage used a randomized, double-blind, controlled design (n = 500), while the second stage used a nonrandomized, open design (n = 7000). Stage 1 participants underwent tuberculosis-specific enzyme-linked immunospot assay (T-SPOT.TB), tuberculin skin test (TST), and EC skin test (ECST). Stage 2 participants only received the ECST. The purposes of the first and second stage were to evaluate the diagnostic performance and safety of the ECST, respectively.
RESULTS: At the first stage, the sensitivity of ECST and TST was 89.41% (95% confidence interval [CI], 80.85%-95.04%) and 85.88% (95% CI, 76.64%-92.49%), respectively. The specificity of the ECST and TST was 96.98% (95% CI, 94.79%-98.43%%) and 61.06% (95% CI, 56.07%-65.87%), respectively. The consistency between ECST and T-SPOT.TB was higher than that between TST and T-SPOT.TB (κ = 0.85 and 0.28, respectively). At the second stage, the incidence of adverse drug reactions (ADRs) was 11.75%, with 0.67% graded ≥3. The incidence of ADRs varied among age groups (<18 years, 2.89%; 18-64 years, 11.51%; ≥65 years, 16.98%) and was significantly higher in individuals with pulmonary tuberculosis (46.58%), human immunodeficiency virus infection (33.33%), diabetes mellitus (15.56%), close contacts of patients with tuberculosis (14.35%), and those with allergic histories (11.93%).
CONCLUSIONS: ECST has a satisfactory safety and diagnostic performance profile and is suitable for screening Mycobacterium tuberculosis infection in the community-based population aged ≥6 months. Clinical Trials Registration. NCT05746611.
MeSH terms
- Humans
- Male
- Female
- Adult
- Antigens, Bacterial
- Middle Aged
- Double-Blind Method
- Adolescent
- Young Adult
- Bacterial Proteins
- Recombinant Fusion Proteins
- Tuberculin Test
- Child
- Tuberculosis
- Child, Preschool
- Aged
- Skin Tests
- Sensitivity and Specificity
- Infant
- Mycobacterium tuberculosis
- Enzyme-Linked Immunospot Assay