Safety and Diagnostic Performance of Recombinant Fusion Protein ESAT6-CPF10 Skin Test in A Large Population: A Phase 4 Clinical Trial.

Abstract

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. 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. 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%). 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.