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Safety, Tolerability, and PK of LBP-EC01 in Patients With Lower Urinary Tract Colonization Caused by E. Coli

L

Locus Biosciences

Status and phase

Completed
Phase 1

Conditions

Urinary Tract Infections

Treatments

Drug: Placebo
Drug: LBP-EC01

Study type

Interventional

Funder types

Industry

Identifiers

NCT04191148
LBx-1001

Details and patient eligibility

About

Study LBx-1001 is a multi-center randomized, double-blind study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of LBP-EC01 in patients with indwelling urinary catheters, or requiring intermittent catheterization, and/or patients with asymptomatic bacteriuria caused by Escherichia coli (E. coli). This study population has been selected because LBP-EC01 is a phage cocktail where active bacterial host engagement is required to allow for amplification of the phage and evaluation of the safety and PK of the phage cocktail. Eligible patients will require confirmation of colonization with a urine sample taken within 10 days of randomization that cultures contain ≥10^3 E. coli colony forming unit (CFU)/mL, without the patient having clinical signs or symptoms of an active urinary tract infection (UTI) requiring antibiotic treatment. Patients should have E. coli as the primary colonizing bacteria and must not have a secondary bacterial colonization at levels equal to or greater than that seen from E. coli.

Full description

Approximately 30 patients 18 years of age or older with a history of urinary tract infection or colonization caused by E. coli who have indwelling urinary catheters, or who require intermittent catheterization, and/or patients with asymptomatic bacteriuria caused by E. coli colonization (≥10^3 CFU/mL) on microbiological diagnosis, without clinical signs or symptoms of infection requiring antibiotic treatment will be enrolled. Patients will be screened for presence of E. coli colonization (≥10^3 CFU/mL) prior to randomization and evaluated for potential bacterial susceptibility to LBP-EC01.

Secondary Objective: To evaluate the pharmacodynamics (PD) of LBP-EC01. Exploratory Objective: To explore the influence of LBP-EC01 on the urinary tract microbiota.

Enrollment

36 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  1. Provision of signed and dated informed consent form.

  2. Stated willingness to comply with all study procedures and availability for the duration of the study.

  3. Males or females 18 years of age or older.

  4. Patients with a lower urinary tract colonization caused by E. coli (≥10^3 CFU/mL) and who meet at least one of the following criteria:

    • Has an indwelling urinary catheter and medical documentation of a urinary tract infection by E. coli within the past 12 months
    • Requires intermittent catheterization and medical documentation of a urinary tract infection by E. coli within the past 12 months
    • Has medical documentation of a history of asymptomatic bacteriuria (i.e., lower urinary tract colonization) with E. coli at least once in the past 12 months
  5. Patients must have experience with urinary catheterization or have Medical Monitor approval if the patient does not have prior experience with catheterization.

  6. In good general health as evidenced by medical history and physical examination.

  7. Women of childbearing potential and men with female partners of childbearing potential must use two forms of effective contraception, at least 1 of which is a physical barrier method, during the study and which is recommended to continue for 2 weeks after completing the study.

Exclusion criteria

  1. Patients with clinical signs of active UTI or other infection requiring antimicrobial treatment. These may include dysuria, urinary frequency, urinary urgency, suprapubic discomfort and flank pain in addition to non-specific symptoms of urinary leakage, change in voiding habits, worsening muscle spasm, increasing autonomic dysreflexia, sweating, malaise, and fever or hypothermia. Analgesic use is permitted.

  2. Patients who have received Gram-negative bacteria antimicrobials within 14 days of randomization.

    Note: Patients who are currently only receiving antibiotics with only Gram-positive activity (e.g., vancomycin, daptomycin, linezolid) to treat active infections against Gram-positive non-UTIs can be included in the trial.

  3. Presence of a surgically-modified bladder, except for a repaired ruptured bladder.

  4. History of severe autonomic dysreflexia, which is defined as those patients who have a spinal cord injury and who have had a documented sudden increase in systolic blood pressure of greater than 40 mm Hg due to an irritation or stimulation (including bladder or bowel irritation) below the level of the spinal cord injury. Autonomic dysreflexia can include findings of hypertensive crisis or emergency, clinically significant bradycardia/tachycardia, severe headache or other severe reaction requiring an acute intervention, so consultation with the Medical Monitor should take place if a history of severe autonomic dysreflexia is suspected but not clearly identified.

  5. Active severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, or neurologic disease per the investigator's discretion.

  6. Any malignancies within the past 5 years (except those in remission).

  7. Unless deemed acceptable by the Investigator, prescription drugs, over-the-counter (OTC) medications and supplements that acidify the urine are excluded.

  8. Patients who have had allergic reactions to similar compounds, or any excipients.

  9. Participation in an investigational drug or device study within 1 month (or 7 half-lives of drug, whichever is longer) prior to randomization.

  10. Patients who are pregnant or expecting to conceive, are breast feeding or are planning to breast feed, within 1 month of completion of the study.

Trial design

Primary purpose

Basic Science

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

36 participants in 2 patient groups, including a placebo group

LBP-EC01
Experimental group
Description:
crPhage cocktail
Treatment:
Drug: LBP-EC01
Placebo
Placebo Comparator group
Description:
Lactated Ringer's solution, injection, USP
Treatment:
Drug: Placebo

Trial documents
2

Trial contacts and locations

7

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Data sourced from clinicaltrials.gov

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