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

NCT ID: NCT05488340

Last Updated: 2025-11-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

318 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-13

Study Completion Date

2026-12-31

Brief Summary

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This is a Phase 2 superiority study of LBP-EC01, a recombinant bacteriophage cocktail, with an initial open-label 3-arm pharmacokinetic (PK) lead-in portion of 30 patients to evaluate the optimal dosing regimen to be used in the subsequent 288 patient blinded 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.

Detailed Description

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This study will consist of two parts.

Part 1 - Dose regimen selection: An open-label, 30 patient, 3-arm PK assessment of: Arm 4 (previously 1): LBP-EC01 (approximately 2×10\^12 PFU) given by IU administration on D1 and D2 and LBP-EC01 (approximately 1×10\^11 PFU) IV given as a 1 milliliter (mL) bolus QD from D1 through D3 concomitantly with oral trimethoprim/sulfamethoxazole (TMP 160mg/SMX 800mg) BID from D1 through D3 (6 doses); Arm 5 (previously 2): LBP-EC01 (approximately 2×10\^12 PFU) given by IU administration on D1 and D2 and LBP-EC01 (approximately 1×10\^10 PFU) IV given as a 1 mL bolus QD from D1 through D3 concomitantly with oral TMP/SMX BID from D1 through D3 (6 doses); Arm 6 (previously 3): LBP-EC01 (2×10\^12 PFU) given by IU administration on D1 and D2 and LBP-EC01 (approximately 1×10\^12 PFU) IV given as a 100 mL IV infusion over 2 h on D1 through D3 concomitantly with oral TMP/SMX BID from D1 through D3 (6 doses).

Part 2 - Efficacy, Safety, Tolerability and Pharmacokinetics: A blinded, 288 patient, 1:1 randomized evaluation of the Arm 4 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.

Conditions

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Urinary Tract Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Part 1 - open label, Part 2 - blinded.

Study Groups

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Part 1- Arm 4 (previously 1)

Intraurethral (IU) LBP-EC01 on D1 and D2 with intravenous (IV) LBP-EC01 (1x10\^11 PFU) and oral TMP/SMX on D1 through D3.

Group Type EXPERIMENTAL

LBP-EC01 0.1 x IV dose

Intervention Type DRUG

Intraurethral (IU) dose of two (2) x 6mL vials of LBP-EC01 (approximately 2x10\^12 PFU) diluted in 188 mL of Lactated Ringer's solution on Day 1 and Day 2. Intravenous (IV) dose of 0.6mL of LBP-EC01 (approximately 1x10\^11 PFU) diluted in 0.4mL of Lactated Ringer's solution given on Days 1 through Day 3.

TMP/SMX

Intervention Type DRUG

TMP/SMX (160 mg trimethoprim and 800 mg sulfamethoxazole) given orally BID on Days 1 through 3.

Part 1- Arm 5 (previously 2)

Intraurethral (IU) LBP-EC01 on D1 and D2 with intravenous (IV) LBP-EC01 (1x10\^10 PFU) and oral TMP/SMX on D1 through D3.

Group Type EXPERIMENTAL

LBP-EC01 0.01x IV Dose

Intervention Type DRUG

Intraurethral (IU) dose of two (2) x 6mL vials of LBP-EC01 (approximately 2x10\^12 PFU) diluted in 188 mL of Lactated Ringer's solution on Day 1 and Day 2. Intravenous (IV) dose of 0.06 mL of LBP-EC01 (approximately 1x10\^10 PFU) diluted in 0.94 mL of Lactated Ringer's solution given on Days 1 through Day 3.

TMP/SMX

Intervention Type DRUG

TMP/SMX (160 mg trimethoprim and 800 mg sulfamethoxazole) given orally BID on Days 1 through 3.

Part 1- Arm 6 (previously 3)

Intraurethral (IU) LBP-EC01 on D1 and D2 with intravenous (IV) LBP-EC01 infusion (1x10\^12 PFU) and oral TMP/SMX on D1 through D3.

Group Type EXPERIMENTAL

LBP-EC01 IV Infusion Dose

Intervention Type DRUG

Intraurethral (IU) dose of two (2) x 6mL vials of LBP-EC01 (approximately 2x10\^12 PFU) diluted in 188 mL of Lactated Ringer's solution on Day 1 and Day 2. Intravenous infusion dose of 6mL of LBP-EC01 (approximately 1x10\^12 PFU) diluted in 94 mL of Lactated Ringer's solution given over 2 hours on Days 1 through Day 3.

TMP/SMX

Intervention Type DRUG

TMP/SMX (160 mg trimethoprim and 800 mg sulfamethoxazole) given orally BID on Days 1 through 3.

Part 2: LBP-EC01

LBP-EC01 given by dose regimen selected from Part 1. IU LBP-EC01 on D1 and D2 with IV LBP-EC01 (1x10\^11 PFU) and oral TMP/SMX on D1 through D3.

Group Type EXPERIMENTAL

LBP-EC01

Intervention Type DRUG

Dose regimen selected from Part 1 of LBP-EC01 (1x10\^10 - 1x10\^13 PFU) per dose.

TMP/SMX

Intervention Type DRUG

TMP/SMX (160 mg trimethoprim and 800 mg sulfamethoxazole) given orally BID on Days 1 through 3.

Part 2: Placebo

Placebo given by dose regimen selected from Part 1. IU placebo on D1 and D2 with IV placebo and oral TMP/SMX on D1 through D3.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Dose regimen selected from Part 1 of placebo (Tris buffer).

TMP/SMX

Intervention Type DRUG

TMP/SMX (160 mg trimethoprim and 800 mg sulfamethoxazole) given orally BID on Days 1 through 3.

Interventions

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LBP-EC01 0.1 x IV dose

Intraurethral (IU) dose of two (2) x 6mL vials of LBP-EC01 (approximately 2x10\^12 PFU) diluted in 188 mL of Lactated Ringer's solution on Day 1 and Day 2. Intravenous (IV) dose of 0.6mL of LBP-EC01 (approximately 1x10\^11 PFU) diluted in 0.4mL of Lactated Ringer's solution given on Days 1 through Day 3.

Intervention Type DRUG

LBP-EC01 0.01x IV Dose

Intraurethral (IU) dose of two (2) x 6mL vials of LBP-EC01 (approximately 2x10\^12 PFU) diluted in 188 mL of Lactated Ringer's solution on Day 1 and Day 2. Intravenous (IV) dose of 0.06 mL of LBP-EC01 (approximately 1x10\^10 PFU) diluted in 0.94 mL of Lactated Ringer's solution given on Days 1 through Day 3.

Intervention Type DRUG

LBP-EC01 IV Infusion Dose

Intraurethral (IU) dose of two (2) x 6mL vials of LBP-EC01 (approximately 2x10\^12 PFU) diluted in 188 mL of Lactated Ringer's solution on Day 1 and Day 2. Intravenous infusion dose of 6mL of LBP-EC01 (approximately 1x10\^12 PFU) diluted in 94 mL of Lactated Ringer's solution given over 2 hours on Days 1 through Day 3.

Intervention Type DRUG

Placebo

Dose regimen selected from Part 1 of placebo (Tris buffer).

Intervention Type DRUG

LBP-EC01

Dose regimen selected from Part 1 of LBP-EC01 (1x10\^10 - 1x10\^13 PFU) per dose.

Intervention Type DRUG

TMP/SMX

TMP/SMX (160 mg trimethoprim and 800 mg sulfamethoxazole) given orally BID on Days 1 through 3.

Intervention Type DRUG

Other Intervention Names

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1x10^11 PFU IV dose 1x10^10 PFU IV Dose 1x10^12 PFU IV Infusion Dose

Eligibility Criteria

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Inclusion Criteria

* History of UTI in the past 12 months and prior or current uUTI caused by AMR E. coli (as single pathogen or part of polymicrobial infection where E. coli is the predominant pathogen). Please note that the current infection can be used to meet the requirement of AMR E. coli documentation.
* Able to supply a mid-stream, clean catch urine sample for microbiological analysis.
* Active acute uUTI infection defined by:

a. 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 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 continuous low dose antimicrobial prophylaxis and/or will maintain the same practices for post-coital antimicrobial prophylaxis to prevent UTI, as during the prior 12-months, 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

* 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 5 days prior to Screening unless the recovered pathogen demonstrates resistance to the initial antibiotic and clinical symptoms persist. In postmenopausal women vaginal estrogen replacement therapy is permitted so long as patient meets all other eligibility criteria, that the dose and regimen has be stable for \> 3 months from Screening (D1/V1), and that there is no planned change to therapy through the 6-month follow-up period or study discontinuation.
* Clinical symptoms for more than 5 days before Screening.
* Presence of indwelling urinary bladder catheters, urinary tract anatomical abnormalities that increase UTI risk or lead to a post void residual (PVR) urine volume \> 150mL, poorly controlled diabetes mellitus (diagnosed but is not being treated/managed by a physician's care or HbA1c \>8), current symptomatic or larger than 5mm renal calculi, or advanced renal dysfunction (determined by eGFR \< 45 mL/min/1.73 m2). Patients with vaginal prolapse beyond the hymen with Valsalva (e.g., when coughing).
* Individuals considered to be immunocompromised.
* 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.
* Pregnant or nursing women.
* 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.
* 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.
* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Parexel

INDUSTRY

Sponsor Role collaborator

Locus Biosciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paul Kim

Role: STUDY_DIRECTOR

Locus Biosciences

Locations

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Research Site 138

Fresno, California, United States

Site Status COMPLETED

Research Site 131

Lancaster, California, United States

Site Status RECRUITING

Research Site 123

Los Angeles, California, United States

Site Status RECRUITING

Research Site 125

Montebello, California, United States

Site Status RECRUITING

Research Site 137

San Diego, California, United States

Site Status RECRUITING

Research Site 126

Tustin, California, United States

Site Status RECRUITING

Research Site 102

Doral, Florida, United States

Site Status RECRUITING

Research Site 140

Jensen Beach, Florida, United States

Site Status COMPLETED

Research Site 103

Miami, Florida, United States

Site Status RECRUITING

Research Site 149

Miami, Florida, United States

Site Status RECRUITING

Research Site 120

Boston, Massachusetts, United States

Site Status COMPLETED

Research Site 118

Winston-Salem, North Carolina, United States

Site Status COMPLETED

Countries

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United States

Central Contacts

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Locus Clinical Operations

Role: CONTACT

(919) 495-4510

Paul Kim

Role: CONTACT

(919) 495-4510

Facility Contacts

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J. Truong, MD

Role: primary

J. Kowalczyk

Role: primary

J. Alarcon

Role: primary

L. Burnett, MD

Role: primary

L. Gabal

Role: primary

B. Penafiel

Role: primary

Y. Rodriguez

Role: primary

M. Ramos

Role: primary

References

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Kim P, Sanchez AM, Penke TJR, Tuson HH, Kime JC, McKee RW, Slone WL, Conley NR, McMillan LJ, Prybol CJ, Garofolo PM. 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 Dec;24(12):1319-1332. doi: 10.1016/S1473-3099(24)00424-9. Epub 2024 Aug 9.

Reference Type DERIVED
PMID: 39134085 (View on PubMed)

Other Identifiers

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LBx-2001

Identifier Type: -

Identifier Source: org_study_id

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