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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05488340
Recruitment Status : Recruiting
First Posted : August 4, 2022
Last Update Posted : March 2, 2023
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
Locus Biosciences

Study Description
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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 0.1 x IV dose Drug: LBP-EC01 0.01x IV Dose Drug: LBP-EC01 IV Infusion Dose Drug: Placebo Drug: LBP-EC01 Drug: TMP/SMX 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 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, 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
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Study Type : Interventional  (Clinical Trial)
Estimated 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 : July 13, 2022
Estimated Primary Completion Date : June 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Drug: 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.
Other Name: 1x10^11 PFU IV dose

Drug: TMP/SMX
TMP/SMX (160 mg trimethoprim and 800 mg sulfamethoxazole) given orally BID on Days 1 through 3.
Experimental: 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.
 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.
Other Name: 1x10^10 PFU IV Dose

Drug: TMP/SMX
TMP/SMX (160 mg trimethoprim and 800 mg sulfamethoxazole) given orally BID on Days 1 through 3.
Experimental: 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.
 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.
Other Name: 1x10^12 PFU IV Infusion Dose

Drug: TMP/SMX
TMP/SMX (160 mg trimethoprim and 800 mg sulfamethoxazole) given orally BID on Days 1 through 3.
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
Placebo given by dose regimen selected from Part 1 and oral 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
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Primary Outcome Measures :
  1. 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 [ Time Frame: Day 1 to Day 5 ]
    The regimen for LBP-EC01 when used concomitantly with TMP/SMX which optimizes pharmacokinetics (PK) for LBP-EC01 will be selected.

  2. 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 [ Time Frame: 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 :
  1. Part 1: Number of patients with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 to Day 34 ]
    The safety and tolerability of LBP-EC01 when given with TMP/SMX will be assessed.

  2. Part 1: Number of patients with immunogenicity [ Time Frame: 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.

  3. Part 2: Proportion of patients with MDR E. coli achieving maintenance of clinical and microbiologic response at Day 21 [ Time Frame: 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.

  4. 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 [ Time Frame: 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.

  5. Part 2: Proportion of patients with E. coli achieving maintenance of clinical and microbiologic response at Day 21 [ Time Frame: 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.

  6. Part 2: Proportion of patients with recurrence of uUTI episodes caused by E. coli within a 6-month follow-up period [ Time Frame: 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
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

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 E. 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:

    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/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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05488340


Contacts
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Contact: William Slone (919) 495-4510 will.slone@locus-bio.com
Contact: Paul Kim (919) 495-4510 Paul.kim@locus-bio.com

Locations
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United States, Alabama
Research Site 104 Recruiting
Anniston, Alabama, United States, 36207
Contact: S. Pulliam         
United States, California
Research Site 105 Recruiting
Irvine, California, United States, 92604
Contact: J. Urrutia         
United States, Florida
Research Site 102 Recruiting
Doral, Florida, United States, 33166
Contact: B. Penafiel         
Research Site 107 Recruiting
Miami, Florida, United States, 33165
Contact: L. Lopez         
Research Site 106 Recruiting
Miami, Florida, United States, 33173
Contact: A. Gonzalez         
Research Site 103 Recruiting
Miami, Florida, United States, 33176
Contact: Y. Rodriguez         
Research Site 100 Recruiting
Palmetto Bay, Florida, United States, 33157
Contact: S. Chang         
United States, Texas
Research Site 108 Recruiting
Forney, Texas, United States, 75126
Contact: Jennifer Jasso         
Sponsors and Collaborators
Locus Biosciences
Parexel
Investigators
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Study Director: Paul Kim Locus Biosciences
More Information
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Responsible Party: Locus Biosciences
ClinicalTrials.gov Identifier: NCT05488340    
Other Study ID Numbers: LBx-2001
First Posted: August 4, 2022    Key Record Dates
Last Update Posted: March 2, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Locus Biosciences:
LBP-EC01
Urinary tract infection
E. coli
Bacteriophage
 Phage
crPhage
Recombinant bacteriophage
Additional relevant MeSH terms:
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Infections
Urinary Tract Infections
Urologic Diseases
Female Urogenital Diseases
 Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases