Clinical trial NCT05488340: A Study of LBP-EC01 in the Treatment of Acute Uncomplicated UTI Caused by Drug Resistant E. Coli (ELIMINATE Trial)
Official title: A Phase 2, 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 Drug Resistant E. Coli
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Urinary Tract Infections
Keywords: LBP-EC01
Urinary tract infection
E. coli
Bacteriophage
Phage
crPhage
Recombinant bacteriophage
Lead sponsor: Locus Biosciences
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2022-08-04
Enrollment: 318
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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, 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Day 1 to Day 5
measure: 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).
timeFrame: Day 10
Secondary outcomes:
measure: Part 1: Number of patients with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 to Day 34
measure: Part 1: Number of patients with immunogenicity
timeFrame: Baseline Day 1 to Day 2, Day 5, Day 10, Day 34/Early Termination [ET]) post-hoc
measure: Part 2: Proportion of patients with antimicrobial drug resistant (AMR) E. coli achieving maintenance of combined clinical and microbiologic response (CCMR) at Day 21.
timeFrame: Day 21
measure: Part 2: Proportion of patients with CCMR of uUTI caused by E. coli at Day 10/TOC.
timeFrame: Day 10
measure: Part 2: Proportion of patients with CCMR of uUTI caused by multi-drug resistant (MDR) E. coli at Day 10/TOC.
timeFrame: Day 21
measure: Part 2: Proportion of patients with MDR E. coli achieving maintenance of CCMR at Day 21.
timeFrame: Within the 6-month follow-up period
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site 115
state: Alabama
city: Chula Vista
country: United States
facility: Research Site 143
state: California
city: Fresno
country: United States
facility: Research Site 138
state: California
city: Lancaster
country: United States
facility: Research Site 131
state: California
city: Los Angeles
country: United States
facility: Research Site 123
state: California
city: Montebello
country: United States
facility: Research Site 125
state: California
city: Orange
country: United States
facility: Research Site 139
state: California
city: San Diego
country: United States
facility: Research Site 137
state: California
city: Tustin
country: United States
facility: Research Site 126
state: California
city: Doral
country: United States
facility: Research Site 102
state: Florida
city: Jensen Beach
country: United States
facility: Research Site 140
state: Florida
city: Miami
country: United States
facility: Research Site 103
state: Florida
city: Decatur
country: United States
facility: Research Site 119
state: Georgia
city: Northbrook
country: United States
facility: Research Site 117
state: Illinois
city: Owings Mills
country: United States
facility: Research Site 128
state: Maryland
city: Boston
country: United States
facility: Research Site 120
state: Massachusetts
city: Royal Oak
country: United States
facility: Research Site 114
state: Michigan
city: Winston-Salem
country: United States
facility: Research Site 118
state: North Carolina
city: Edinburg
country: United States
facility: Research Site 141
state: Texas
city: Galveston
country: United States
facility: Research Site 122
state: Texas
city: Richmond
country: United States
facility: Research Site 127
state: Virginia
Study officials:
affiliation: Locus Biosciences
name: Paul Kim
role: STUDY_DIRECTOR
References: