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

NCT05488340 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: LBx-2001
• Study Type: interventional
• Target: 318
• Locations: 1 country
• Sites: 17

Brief Summary

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.

Conditions

Urinary Tract Infections

Keywords

LBP-EC01; Urinary tract infection; E. coli; Bacteriophage; Phage; crPhage; Recombinant bacteriophage

Outcome Measures

Primary Outcomes (2)

• 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

  The regimen for LBP-EC01 when used concomitantly with TMP/SMX which optimizes pharmacokinetics (PK) for LBP-EC01 will be selected.

  Day 1 to Day 5

• Part 2: Proportion of patients with resolution of clinical symptoms and microbiologic response of uUTI caused by drug resistant E. coli as defined at Day 10 test of cure (TOC).

  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 clinical symptoms and demonstration of microbiologic response (CCMR) of acute uUTI caused by drug resistant E. coli will be assessed.

  Day 10

Secondary Outcomes (6)

• Part 1: Number of patients with Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Day 1 to Day 34

• Part 1: Number of patients with immunogenicity

  Baseline Day 1 to Day 2, Day 5, Day 10, Day 34/Early Termination [ET]) post-hoc

• Part 2: Proportion of patients with antimicrobial drug resistant (AMR) E. coli achieving maintenance of combined clinical and microbiologic response (CCMR) at Day 21.

  Day 21

• Part 2: Proportion of patients with CCMR of uUTI caused by E. coli at Day 10/TOC.

  Day 10

• Part 2: Proportion of patients with CCMR of uUTI caused by multi-drug resistant (MDR) E. coli at Day 10/TOC.

  Day 21

Study Arms (5)

Part 1- Arm 4 (previously 1)

EXPERIMENTAL

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

Drug: LBP-EC01 0.1 x IV dose; Drug: TMP/SMX

Part 1- Arm 5 (previously 2)

EXPERIMENTAL

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

Drug: LBP-EC01 0.01x IV Dose; Drug: TMP/SMX

Part 1- Arm 6 (previously 3)

EXPERIMENTAL

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.

Drug: LBP-EC01 IV Infusion Dose; Drug: TMP/SMX

Part 2: LBP-EC01

EXPERIMENTAL

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.

Drug: LBP-EC01; Drug: TMP/SMX

Part 2: Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: TMP/SMX

Interventions

LBP-EC01 0.1 x IV dose 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.

Also known as: 1x10^11 PFU IV dose

Part 1- Arm 4 (previously 1)

LBP-EC01 0.01x IV Dose 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.

Also known as: 1x10^10 PFU IV Dose

Part 1- Arm 5 (previously 2)

LBP-EC01 IV Infusion Dose 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.

Also known as: 1x10^12 PFU IV Infusion Dose

Part 1- Arm 6 (previously 3)

Placebo DRUG

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

Part 2: Placebo

LBP-EC01 DRUG

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

Part 2: LBP-EC01

TMP/SMX DRUG

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

Part 1- Arm 4 (previously 1); Part 1- Arm 5 (previously 2); Part 1- Arm 6 (previously 3); Part 2: LBP-EC01; Part 2: Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Locus Biosciences: lead
• Parexel: collaborator

Study Sites (17)

Research Site 138

Fresno, California, 93710, United States

COMPLETED

Research Site 131

Lancaster, California, 93534, United States

RECRUITING

Research Site 123

Los Angeles, California, 90027, United States

RECRUITING

Research Site 125

Montebello, California, 90640, United States

COMPLETED

Research Site 152

Murrieta, California, 92563, United States

RECRUITING

Research Site 137

San Diego, California, 92037, United States

RECRUITING

Research Site 126

Tustin, California, 92780, United States

RECRUITING

Research Site 102

Doral, Florida, 33166, United States

RECRUITING

Research Site 151

Hialeah, Florida, 33013, United States

RECRUITING

Research Site 140

Jensen Beach, Florida, 34957, United States

COMPLETED

Research Site 103

Miami, Florida, 33176, United States

RECRUITING

Research Site 149

Miami, Florida, 33176, United States

RECRUITING

Research Site 153

Ocala, Florida, 34473, United States

RECRUITING

Research Site 120

Boston, Massachusetts, 02115, United States

COMPLETED

Research Site 154

St Louis, Missouri, 63141, United States

RECRUITING

Research Site 145

Raleigh, North Carolina, 27708, United States

RECRUITING

Research Site 118

Winston-Salem, North Carolina, 27157, United States

COMPLETED

Related Publications (1)

• 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.

  PMID: 39134085 DERIVED

MeSH Terms

Conditions

Urinary Tract Infections; Escherichia coli Infections

Interventions

Trimethoprim, Sulfamethoxazole Drug Combination

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Paul Kim

  Locus Biosciences

  STUDY DIRECTOR

Central Study Contacts

Locus Clinical Operations

CONTACT

(919) 495-4510; clinicaloperations@locus-bio.com

Paul Kim

CONTACT

(919) 495-4510; Paul.kim@locus-bio.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part 1 - open label, Part 2 - blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2022
• First Posted: August 4, 2022
• Study Start: July 13, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (17)