Results
poisoning, late-stage disease, death, suffocation, peripheral ascending polyneuropathy, acute pulmonary oedema, cord prolapse, deaths, acoziborole
NEONATAL INFECTION, SUFFOCATION, ACUTE PULMONARY OEDEMA, ADVERSE EVENTS, DISEASE, THYROID, SECONDARY, ADVERSE EVENT, EVENTS, EXTRAPULMONARY TUBERCULOSIS, COMPLICATIONS
Between Oct 11, 2016, and March 25, 2019, 260 patients were screened, of whom 52 were ineligible and 208 were enrolled (167 with late-stage and 41 with early-stage or intermediate-stage gambiense HAT; Patient dispositionGambiense HAT refers to HAT caused by Trypanosomes in the CSF were detected in 139 (83%) of 167 patients with late-stage disease and 128 (77%) of those had more than 100 WBC per μl of CSF (Baseline characteristics (modified intention-to-treat population)Data are presented as n (%) or mean (SD).Documented with video.WBC count per μL of cerebrospinal fluid from baseline to 18 months follow-up in the modified intention-to-treat populationData are n, mean (SD), or median (IQR). WBC=white blood cells.In terms of the primary efficacy endpoint, treatment success rate at 18 months was 95·2% (95% CI 91·2–97·7) reached in 159 of 167 patients with late-stage gambiense HAT (mITT population) and 98·1% (95·1–99·5) reached in 159 of 162 patients (evaluable population). For secondary efficacy endpoints, the treatment success rates at 6, 12, and 18 months were similar (Complementary post-hoc analysis after adjustment for key baseline characteristics (because patients in pivotal NECT had less severe disease than in our study) showed that the success rates of acoziborole and NECT were similar regardless of disease severity (based on CSF WBC count; The overall frequency of all signs and symptoms of HAT decreased during the study from day 15, reaching a low frequency or absence at 18 months (Summary of all adverse events in the treated populationData are presented as n (%), unless stated otherwise. TEAE=treatment-emergent adverse event.Serious treatment-emergent adverse events were reported in 21 (10%) of 208 patients, but none of these events were considered drug-related (During the study, incidental pregnancies were detected within 6 months of acoziborole treatment in seven women; in utero exposure was considered in six of these women, all of which were full-term pregnancies without complications. Four children were born without health problems (pregnancies diagnosed on days 11, 30, 85, and 140 after dosing), and three newborn babies died (death at delivery due to cord prolapse and no assistance for 10 h; acute neonatal infection; and accidental suffocation during breastfeeding). Five further pregnancies and deliveries were observed outside of the reporting period (>6 months after drug intake) without any health complications.Four deaths occurred after dosing in the treated population (poisoning on day 24, worsening of progressive peripheral ascending polyneuropathy on day 9, extrapulmonary tuberculosis on day 233, and acute pulmonary oedema on day 387) and none were considered related to treatment or HAT. The laboratory results showed no substantial changes from baseline in haematology parameters, liver enzymes (alanine and aspartate aminotransferases), and other biochemistry data. Thyroid function tests (thyroid-stimulating hormone [TSH], free tri-iodothyronine [TPharmacokinetic analysis revealed a T