Novel TB skin test as accurate as IGRAs in phase 3 trials

Results from two phase 3 clinical trials recently demonstrated that a new tuberculosis skin test was safe, easy to use and comparable in accuracy to an interferon gamma release assay.

The C-Tb skin test, which measures the body’s immune response to the EAST-6 and CFP10 TB antigens, is administered in a similar fashion to a tuberculin skin test (TST), and results are interpreted by measuring skin induration 2 to 3 days later. While the size of induration is often adjusted to increase the accuracy of TST testing in different populations, C-Tb uses a universal 5-mm or larger induration to identify TB infection across all patient groups.

Figure 1. An image of Mycobacterium tuberculosis.

Source: ATS

According to study researcher Morten Ruhwald, MD, PhD, head of human immunology at Statens Serum Institut in Denmark, which developed the test, C-Tb combines the “field friendliness of the PPD-based tuberculin skin test with the high specificity of interferon gamma release assays, or IGRAs.”

At the American Thoracic Society International Conference in San Francisco, Ruhwald presented data from TESEC-06 and TESEC-05 — double blind clinical trials that compared C-Tb with TST and IGRA testing (QuantiFERON-TB Gold In-Tube test, Qiagen Group). TESEC-06 was conducted at 13 sites across Catalonia, Galicia and Basque Country in Spain, and included 979 adults with various risk profiles of Mycobacterium tuberculosis infection. TESEC-05 enrolled more than 1,000 participants with TB symptoms in South Africa, including young children and patients with HIV — two populations in which TST and IGRA testing are known to have limited sensitivity.

Results of the first clinical trial showed that the safety profile of C-Tb was acceptable and comparable to that of TST. Both C-Tb and IGRA had a specificity of 97%, and unlike TST, which had a specificity of 62%, C-Tb was unaffected by prior bacille Calmette-Guérin vaccination and therefore less likely to give a false-positive result. According to the researchers, C-Tb was highly concordant to IGRA in 95% of participants, and the sensitivity of C-Tb and IGRA was similar in patients with confirmed TB (77% vs. 81%).

In the second clinical trial, the researchers found that the accuracy of all three tests was diminished among participants with HIV. However, C-Tb testing was more robust in HIV patients with low CD4 T-cell counts. Among children aged younger than 5 years, C-Tb was comparable to TST and IGRA in identifying TB infection.

According to the researchers, C-Tb’s ease of use and high specificity could help improve targeted treatment of patients with M. tuberculosis infection in resource-limited settings where IGRAs are too complicated to use.

Statens Serum Institut currently is seeking regulatory approval of C-Tb and a commercial partner to market the test. Although the cost of a C-Tb test has not been established, it is expected to be significantly less than an IGRA, according to Ruhwald. – by John Schoen

Reference:

Ruhwald M, et al. Abstract 9953. Presented at: American Thoracic Society International Conference; May 13-18, 2016; San Francisco.

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