Safety and Diagnostic Performance of Recombinant Fusion Protein ESAT6-CPF10 Skin Test in A Large Population: A Phase IV Clinical Trial

Abstract Background This study aimed to evaluate the safety and diagnostic performance of recombinant fusion protein ESAT6-CPF10 (EC) in a community-based population aged ≥6 months. Methods We conducted a two-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 non-randomized, 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% 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 (Kappa=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 (TB) (46.58%), HIV infection (33.33%), diabetes mellitus (15.56%), close contacts of TB patients (14.35%), and those with allergic histories (11.93%). Conclusions EC has a satisfactory safety and diagnostic performance profile, and it is suitable for screening Mycobacterium tuberculosis (MTB) infection in the community-based population aged ≥6 months. Clinical Trials Registration NCT05746611.