The following is a summary of “Efficacy and safety of fexinidazole for treatment of chronic indeterminate Chagas disease (FEXI-12): a multicentre, randomised, double-blind, phase 2 trial,” published in the January 2024 issue of Infectious Diseases by Pinazo et al.

Chagas disease, affecting over six million globally, particularly in Latin America, faces limited access to diagnosis and treatment, with outdated drugs and significant adverse reactions hindering therapeutic success despite promising but previously poorly tolerated options like fexinidazole.

Researchers conducted a retrospective study to assess the efficacy and tolerability of fexinidazole at reduced doses and shorter treatment durations for Chagas disease.

They conducted a phase 2 trial, enrolling adult patients aged 18–60 with confirmed Trypanosoma cruzi infection via serology and PCR without signs of organ involvement. 3 fexinidazole regimens were evaluated as 600 mg once daily for 10 days (total dose 6.0 g), 1200 mg daily for 3 days (total dose 3.6 g), and 600 mg daily for 3 days followed by 1200 mg daily for 4 days (total dose 6.6 g). These were compared with a historical placebo control group (n=47). The primary endpoint was sustained negative PCR results at the end of treatment and on each visit up to four months of follow-up.

The results showed that 45 patients (n=15 for each group) were enrolled (between October 16, 2017, and August 7, 2018), with 43 completing the study. 8 (19%) out of 43 fexinidazole-treated patients reached the primary endpoint, compared to 6 (13%) out of 46 in the historical control group. The mean parasite load experienced a notable decline post-treatment. Still, it rebounded after 10 weeks. 5 participants encountered seven grade 3 adverse events, including carpal tunnel, sciatica, device infection, pneumonia, staphylococcal infection, and joint and device dislocation. Two participants discontinued treatment due to adverse events unrelated to fexinidazole.

Investigators concluded that while safe, fexinidazole monotherapy failed to treat Trypanosoma cruzi infection effectively, halting its development for Chagas disease.

Source: thelancet.com/journals/laninf/article/PIIS1473-3099(23)00651-5/fulltext#%20