Background
TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for
the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not
been evaluated.
Methods and Findings
In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of
TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment
capacity was reached, patients were enrolled into a concurrent observational cohort. The
primary outcome was survival to day 14 after admission, excluding patients who died within
48 h of admission.
After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary
was reached, indicating a probability of survival to day 14 of 0.55, and enrolment was
stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients
was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108
, 6.66 × 109
). Two of the TKM-
130803 recipients died within 48 h of admission and were therefore excluded from the primary
outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently
survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions
were well tolerated, with 56 doses administered and only one possible infusionrelated
reaction observed. Three patients were enrolled in the observational cohort, of
whom two died.
Conclusions
Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult
patients with severe EVD was not shown to improve survival when compared to historic
controls.