ELIMINATE trial: uUTI regimen demonstrates initial tolerability, efficacy

Initial data from the phase 2 ELIMINATE trial (NCT05488340) showed that treatment with LBP-EC01, a CRISPR-Cas3-enhanced bacteriophage cocktail, in combination with oral trimethoprim-sulfamethoxazole (TMP-SMX) was well-tolerated and resulted in rapid and durable reductions of Escherichia coli (E coli) in patients with uncomplicated urinary tract infection (uUTI) due to E coli.¹

The ELIMINATE trial remains ongoing.

Specifically, the investigators noted that a regimen consisting of intraurethral LBP-EC01, 3 days of concurrent intravenous LBP-EC01 (1 × 1010 plaque-forming units [PFU]), and oral trimethoprim-sulfamethoxazole (TMP-SMX) twice a day demonstrated the most promise.

In total, the study included 39 patients in the intent-to-treat population.

The authors noted, “Participants were initially randomized in a 1:1:1 ratio into 3 treatment groups, but this part of the trial was terminated on the recommendation of the safety review committee after a non-serious tolerability signal was observed based on systemic drug exposure.”

Following an update of the study protocol, 31 patients were randomly assigned to group A (n = 11), group B (n = 10), and group C (n = 10).

All groups were dosed with intraurethral 2 × 1012 PFU of LBP-EC01 on days 1 and 2 by catheter plus 3 daily intravenous doses of LBP-EC01 on days 1-3. This consisted of 1 mL of 1 × 1010 PFU intravenous bolus in group A, 1 mL of 1 × 109 PFU intravenous bolus in group B, and a 2h 1 × 1011 PFU intravenous infusion in 100 mL of sodium lactate solution in group C.

Data showed a maximum mean urine drug concentration 6·3 × 108 PFU per mL. Maximum mean concentrations were consistent across intraurethral dosing. Conversely, blood plasma level of bacteriophages was intravenous dose-dependent. Maximum mean concentrations were 4·0 × 103 in group A, 2·5 × 103 in group B, and 8·0 × 105 in group C.

A rapid reduction in E coli in the urine was observed among 10 of 16 evaluable patients at 4 hours following the first treatment. This was maintained at day 10 and accompanied by a complete resolution of UTI symptoms in these patients.

Regarding safety, there were 44 adverse events (AEs) reported across 18 of 39 (46%) patients. More AEs were reported among patients who received higher intravenous doses. No serious AEs were observed.

The authors noted, “Three patients in groups 1 to 3 and one patient in group C, all of whom received 1 × 1011 LBP-EC01 intravenously, had non-serious tachycardia and afebrile chills after the second intravenous dose.”

Overall, the open-label phase 2 study enrolled adult female participants with uUTI between August 2022 and August 2023. Patients were enrolled throughout 6 clinical trial sites in the United States.

The primary end point was the level of LBP-EC01 in urine and the blood across the treatment period and at over 48 hours after the last dose. This was assessed in patients who received at least 1 dose of LBP-EC01 and had concentration-time data available throughout the days 1-3 dosing period. The secondary end point was safety, which was assessed in patients who received at least 1 dose of LBP-EC01.

The study remains ongoing to further assess the dosing regimen identified in this first phase of study. Final study completion is anticipated for December 2025.²

The authors concluded, “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.”

Reference

1. Kim P, Sanchez AM, Penke TJR, et al. Safety, pharmacokinetics, and pharmacodynamics of LBP-EC01, a CRISPR-Cas3-enhanced bacteriophage cocktail, in uncomplicated urinary tract infections due to Escherichia coli (ELIMINATE): the randomised, open-label, first part of a two-part phase 2 trial. Lancet Infect Dis. 2024:S1473-3099(24)00424-9. doi:10.1016/S1473-3099(24)00424-9

2. A Study of LBP-EC01 in the treatment of acute uncomplicated UTI caused by drug resistant E. Coli (ELIMINATE Trial) (ELIMINATE). ClinicalTrials.gov. Last updated October 22, 2024. Accessed November 1, 2024. https://clinicaltrials.gov/study/NCT05488340