A Study of LBP-EC01 in the Treatment of Acute Uncomplicated UTI Caused by Multi-drug Resistant E. Coli (ELIMINATE Trial)

Sponsor

Locus Biosciences (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05488340

Collaborator

Parexel (Industry)

580

Enrollment

Locations

Arms

40.6

Anticipated Duration (Months)

82.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 2/3 superiority study of LBP-EC01, a recombinant bacteriophage cocktail, with an initial 3-arm pharmacokinetic (PK) lead-in portion of 30 patients to evaluate the optimal dosing regimen to be used in the subsequent 550 patient portion of the study which will be randomized 1:1 comparing LBP-EC01 + antibiotic versus placebo + antibiotic in patients with a history of prior urinary tract infection (UTI) cased by E. coli. All patients will be required to have an active acute uncomplicated UTI at baseline.

Condition or Disease	Intervention/Treatment	Phase
Urinary Tract Infections	Drug: LBP-EC01 Drug: LBP-EC01 Drug: LBP-EC01 Drug: Placebo Drug: LBP-EC01 Drug: TMP/SMX Drug: Calcium carbonate	Phase 2/Phase 3

Detailed Description

This study will consist of two parts.

Part 1 - Dose regimen selection: An open-label, 30 patient, 3-arm PK assessment of: Arm 1:

Two (2) doses of 6mL of LBP-EC01 (1x10^{10 -1x10}13 PFU) given IV 4hrs apart on Days 1 through 5 and trimethoprim (TMP)/sulfamethoxazole (SMX) (160 mg TMP and 800 mg SMX) given orally BID on Days 1 through 3; Arm 2: The same dosing regimen as Arm 1 with addition of an intravesicular administration on Day 1 of 6mL of LBP-EC01 (1x10^{10 -1x10}13 PFU) diluted in 94 mL of 0.9% NaCl; Arm 3: 6mL of LBP-EC01 (1x10^{10 -1x10}13 PFU)administered IV 4hrs apart on Days 1-2 followed by 6mL of LBP-EC01 taken orally with 14mL of water 4hrs apart on Days 3-5 with TMP/SMX (160 mg trimethoprim and 800 mg sulfamethoxazole) given orally BID on Days 1 through 3.

Part 2 - Efficacy, Safety, Tolerability and Pharmacokinetics: A blinded, 550 patient, 1:1 randomized evaluation of the dose regimen selected from Part 1 versus placebo + antibiotic (TMP/SMX -160 mg TMP and 800 mg SMX) given orally BID on Days 1 through 3.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

580 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Part 1 - open label, Part 2 - blinded.

Primary Purpose:

Treatment

Official Title:

A Phase 2/3, Double-blind, Randomized, Active-controlled Evaluation of the Safety, Tolerability, Pharmacokinetics and Efficacy of LBP-EC01 in the Treatment of Acute Uncomplicated Urinary Tract Infection Caused by Multidrug Resistant E. Coli

Actual Study Start Date :

Jul 13, 2022

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1- Arm 1 Intravenous (IV) LBP-EC01 and oral TMP/SMX.	Drug: LBP-EC01 Two doses of 6mL of LBP-EC01 (1x10^10 -1x10^13 PFU) given IV 4hrs apart on Days 1 through 5. Drug: TMP/SMX TMP/SMX (160 mg trimethoprim and 800 mg sulfamethoxazole) given orally BID on Days 1 through 3.
Experimental: Part 1- Arm 2 Intraurethral (IU) loading dose of LBP-EC01 followed by IV LBP-EC01 and oral TMP/SMX.	Drug: LBP-EC01 Initial intraurethral (IU) loading dose of 6mL of LBP-EC01 (1x10^10 -1x10^13 PFU) diluted in 94mL of 0.9mL NaCl on Day 1 and two doses of 6mL of LBP-EC01 (1x10^10 -1x10^13 PFU) given IV 4hrs apart on Days 1 through 5. Drug: TMP/SMX TMP/SMX (160 mg trimethoprim and 800 mg sulfamethoxazole) given orally BID on Days 1 through 3.
Experimental: Part 1- Arm 3 IV LBP-EC01 followed by oral LBP-EC01 and oral TMP/SMX.	Drug: LBP-EC01 Two doses of 6mL of LBP-EC01 (1x10^10 -1x10^13 PFU) given IV 4hrs apart on Days 1-2 followed by two doses of 6mL of LBP-EC01 (1x10^10 -1x10^13 PFU) taken orally with 14mL of water 4hrs apart on Days 3 through 5. Drug: TMP/SMX TMP/SMX (160 mg trimethoprim and 800 mg sulfamethoxazole) given orally BID on Days 1 through 3. Drug: Calcium carbonate Oral calcium carbonate (1000 mg) administered approximately 10-20 minutes prior to each oral dose of LBP-EC01.
Experimental: Part 2: LBP-EC01 LBP-EC01 given by dose regimen selected from Part 1 and oral TMP/SMX.	Drug: LBP-EC01 Dose regimen selected from Part 1 of LBP-EC01 (1x10^10 - 1x10^13 PFU) per dose. Drug: TMP/SMX TMP/SMX (160 mg trimethoprim and 800 mg sulfamethoxazole) given orally BID on Days 1 through 3.
Placebo Comparator: Part 2: Placebo Participants will receive placebo concomitantly with TMP/SMX.	Drug: Placebo Dose regimen selected from Part 1 of placebo (Tris buffer). Drug: TMP/SMX TMP/SMX (160 mg trimethoprim and 800 mg sulfamethoxazole) given orally BID on Days 1 through 3.

Outcome Measures

Primary Outcome Measures

Part 1: Levels of LBP-EC01 in urine and blood measured by quantitative plaquing assay across the treatment period and over 48 h after the last dose [Day 1 to Day 7]
The regimen for LBP-EC01 when used concomitantly with TMP/SMX which optimizes pharmacokinetics (PK) for LBP-EC01 will be selected.
Part 2: Proportion of patients with resolution of clinical symptoms of a uncomplicated urinary tract infection (uUTI) and microbiologic response of uUTI caused by multidrug resistant or multidrug resistance (MDR) E. coli as defined at Day 10 [Day 10]
The efficacy of LBP-EC01 when used concomitantly with TMP/SMX compared to placebo when used concomitantly with TMP/SMX on resolution of acute uUTI symptoms and demonstration of microbiologic response of acute uUTI caused by MDR E. coli will be assessed.

Secondary Outcome Measures

Part 1: Number of patients with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Day 1 to Day 34]
The safety and tolerability of LBP-EC01 when given with TMP/SMX will be assessed.
Part 1: Number of patients with immunogenicity [Baseline Day 1 to Day 2, Day 5, Day 10, Day 34/Early Termination [ET]) post-hoc]
The immunogenicity of LBP-EC01 by measuring neutralizing antibody (NAb) levels will be assessed.
Part 2: Proportion of patients with MDR E. coli achieving maintenance of clinical and microbiologic response at Day 21 [Day 21]
The impact of LBP-EC01 when used concomitantly with TMP/SMX compared to placebo when used concomitantly with TMP/SMX on maintenance of clinical (symptom resolution) and microbiologic success in those randomized patients with MDR E. coli uUTI demonstrating an initial response will be assessed.
Part 2: Proportion of patients with resolution of clinical symptoms of an uncomplicated (uUTI) and microbiologic response of uUTI caused by E. coli at Day 10 [Day 10]
The efficacy of LBP-EC01 when used concomitantly with TMP/SMX compared to placebo when used concomitantly with TMP/SMX, on resolution of uUTI symptoms and demonstration of microbiologic response of uUTIs caused by E. coli will be assessed.
Part 2: Proportion of patients with E. coli achieving maintenance of clinical and microbiologic response at Day 21 [Day 21]
The impact of LBP-EC01 when used concomitantly with TMP/SMX compared to placebo when used concomitantly with TMP/SMX on maintenance of clinical (symptom resolution) and microbiologic success in those randomized patients with E. coli uUTI demonstrating an initial response will be assessed.
Part 2: Proportion of patients with recurrence of uUTI episodes caused by E. coli within a 6-month follow-up period [Within the 6-month follow-up period]
Patients will be monitored for 6 months for recurrence of uUTI in those with a documented history of prior E. coli infections of the urinary tract.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

History of recurrent UTI defined as ≥2 UTIs in the past 6 months or ≥ 3 UTIs in the past 12 months prior to Screening (Day 1/Visit 1) with at least one of these caused by

coli (as single pathogen or part of polymicrobial infection where E. coli was the predominant pathogen at quantitation ≥ 1.0 × 10^5 colony forming units [CFU]/mL) based on culture results/documentation.

History of positive urine culture with presence of MDR OR extended spectrum beta-lactamases (ESBL) E. coli within the last 12 months.
Able to supply a mid-stream, clean catch urine sample for microbiological analysis.
Active acute uUTI infection defined by:

Evidence of pyuria: i. >10 white blood cell (WBC)/mL3 on microscopic evaluation of spun, clean, mid-stream urine specimen or >3 WBC/high power field on unspun clean, mid-stream urine specimen, AND/OR ii. Dipstick analysis of a clean, mid-stream urine specimen positive for leukocytes, AND/OR iii. Positive catalase test of a clean, mid-stream urine specimen. AND b. At least 2 of the following signs or symptoms of UTI: dysuria, urinary frequency, urinary urgency, or suprapubic pain"

Willing to comply with all aspects of study design including study restrictions, blood, urine, and stool sampling, and scheduled study visits.
All sexually active female patients of childbearing potential must use highly effective contraception during the study and until 2 weeks after the last dose of study drug treatment.
Agrees to STOP the use of cranberry products, probiotics (Lactobacillus spp), D-mannose, OM-89 (various strains of E. coli), continuous low dose antimicrobial prophylaxis and/or post-coital antimicrobial prophylaxis to prevent UTI for the entire study duration (throughout the 6-month follow-up period or study discharge).
Agrees to not use any prescription or non-prescription medication for the microbiological or symptomatic treatment of the presenting acute uUTI for the first 10 days of the study.
Capable of providing their own signed informed consent form (ICF) prior to any study-related procedures being performed.
If participating in Part 1 of the study, agrees to fast for ≥2 h prior to first dose of study drug on Day 1/Visit 1 except for drinking 240 mL of water with study drug administration.

Exclusion Criteria:

Pregnant or nursing women.
Allergies to excipients of the study drug or antibiotics.
History of autonomic dysreflexia.
History of intravenous (IV) drug abuse or is currently using or has positive results for drugs of abuse at screening.
Signs or symptoms of systemic illness such as fever greater than 38° Centigrade/Celsius, shaking chills, or other clinical manifestations suggestive of complicated UTI.
Treatment with other antibacterial drugs including those that are effective for treatment of the acute uUTI or prevention of recurrent UTI in the 3 days prior to Screening unless the recovered pathogen demonstrates resistance to the initial antibiotic and clinical symptoms persist.
Clinical symptoms for more than 7 days before Screening.
Presence of indwelling urinary bladder catheters, urinary tract anatomical abnormalities, poorly-controlled diabetes mellitus, immunocompromising condition and/or treatment, or advanced renal disfunction.
Clinically significant serious unstable physical illness that in the investigator's opinion prevents patient from completing the study or prevents interpretation or resolution of clinical symptoms.
Exposure to any investigational drugs or other phage therapy 30 days prior to Screening (D1/V1) or prior to participation in this study. Patients who participate in Part 1 are not eligible for participation in Part 2.
Patients who reside in a long-term care facility.
Suspected or confirmed acute coronavirus disease 2019 (COVID-19) or recent COVID-19 infection with ongoing symptoms.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site 104	Anniston	Alabama	United States	36207
2	Research Site 105	Irvine	California	United States	92604
3	Research Site 102	Doral	Florida	United States	33166
4	Research Site 107	Miami	Florida	United States	33165
5	Research Site 106	Miami	Florida	United States	33173
6	Research Site 103	Miami	Florida	United States	33176
7	Research Site 100	Palmetto Bay	Florida	United States	33157