Initial results from the phase 2 ELIMINATE trial suggest that LBP-EC01, a CRISPR-Cas3-enhanced bacteriophage cocktail, in conjunction with oral trimethoprim-sulfamethoxazole (TMP-SMX), shows promise in treating uncomplicated urinary tract infections (uUTIs) caused by Escherichia coli (E. coli). The open-label trial (NCT05488340) demonstrated that the treatment was well-tolerated and led to rapid and sustained reductions in E. coli levels in the urine of affected patients. These findings offer a potential alternative in the face of increasing antibiotic resistance.
The ELIMINATE trial, which is still ongoing, enrolled 39 patients in the intent-to-treat population across six clinical trial sites in the United States between August 2022 and August 2023. Initial randomization into three treatment groups was halted after a tolerability signal was observed. Subsequently, the study protocol was updated, and 31 patients were randomly assigned to three groups (A, B, and C) to assess different dosing regimens of intravenous LBP-EC01 in combination with intraurethral LBP-EC01 and oral TMP-SMX.
Dosing and Pharmacokinetics
All groups received intraurethral LBP-EC01 (2 × 10^12 PFU) on days 1 and 2, plus three daily intravenous doses of LBP-EC01 on days 1-3. Group A received 1 mL of 1 × 10^10 PFU intravenous bolus, group B received 1 mL of 1 × 10^9 PFU intravenous bolus, and group C received a 2-hour 1 × 10^11 PFU intravenous infusion in 100 mL of sodium lactate solution.
Pharmacokinetic data revealed a maximum mean urine drug concentration of 6.3 × 10^8 PFU per mL, consistent across intraurethral dosing. Blood plasma levels of bacteriophages were intravenous dose-dependent, with maximum mean concentrations of 4.0 × 10^3 in group A, 2.5 × 10^3 in group B, and 8.0 × 10^5 in group C.
Efficacy and Safety
Results indicated a rapid reduction in E. coli in the urine of 10 out of 16 evaluable patients within 4 hours of the first treatment. This reduction was maintained at day 10 and was accompanied by a complete resolution of UTI symptoms in these patients. Regarding safety, 44 adverse events (AEs) were reported across 18 of 39 (46%) patients. The incidence of AEs was higher among patients receiving higher intravenous doses. Notably, no serious AEs were observed.
According to the study, "Three patients in groups 1 to 3 and one patient in group C, all of whom received 1 × 10^11 LBP-EC01 intravenously, had non-serious tachycardia and afebrile chills after the second intravenous dose."
The primary endpoint of the trial was the level of LBP-EC01 in urine and blood over the treatment period and 48 hours after the last dose. The secondary endpoint was safety, assessed in patients who received at least one dose of LBP-EC01.
Future Directions
The study is ongoing to further assess the dosing regimen identified in this first phase, with final study completion anticipated for December 2025. The authors concluded that "LBP-EC01 holds promise in providing an alternative therapy for uncomplicated UTIs, with further testing of the group A dosing regimen planned in the controlled, double-blind, second part of ELIMINATE."
