Clinical trial NCT04191148: Safety, Tolerability, and PK of LBP-EC01 in Patients With Lower Urinary Tract Colonization Caused by E. Coli
Official title: A Multi-Center Randomized, Double-Blind Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LBP-EC01 in Patients With Lower Urinary Tract Colonization Caused by E. Coli
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Urinary Tract Infections
Keywords: UTI
Bacteriophage
Phage
Lead sponsor: Locus Biosciences
Sponsor class: INDUSTRY
First posted: 2019-12-09
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2:1 randomized, placebo controlled, blinded study
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment-related Adverse Events as Assessed by DAIDS v2.1
timeFrame: 35 days
measure: Pharmacokinetics of LBP-EC01: Cmax
timeFrame: 28 days
measure: Pharmacokinetics of LBP-EC01: Tmax
timeFrame: 28 days
measure: Pharmacokinetics of LBP-EC01: AUC
timeFrame: 28 days
Secondary outcomes:
measure: Reduction in Urinary E.Coli Burden at Any of the Following Time Points: Day 2, Day 3, Day 5, Day 7 (EOT), Day 14 and Day 28
timeFrame: 28 days
measure: Time to 1 Logarithmic Reduction in Urinary E.Coli Count From Baseline
timeFrame: 28 days
measure: Recurrence of E.Coli Colonization or Incidence of Infection Based on Clinical Signs and Symptoms
timeFrame: 28 days
measure: Changes in Immunoglobulin (Ig)A
timeFrame: 28 days
measure: Changes in IgE
timeFrame: 28 days
measure: Changes in IgG
timeFrame: 28 days
measure: Changes in IgM
timeFrame: 28 days
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group
state: Alabama
city: Irvine
country: United States
facility: Tilda Research
state: California
city: Doral
country: United States
facility: Universal Axon Clinical Research
state: Florida
city: Homestead
country: United States
facility: Universal Axon - Homestead, LL
state: Florida
city: Miami Gardens
country: United States
facility: AMPM Research Clinic
state: Florida
city: Palmetto Bay
country: United States
facility: Innovation Medical Research Center
state: Florida
city: Charleston
country: United States
facility: Ralph H. Johnson VA Medical Center
state: South Carolina
Study officials:
References:
citation: Lenneman BR, Fernbach J, Loessner MJ, Lu TK, Kilcher S. Enhancing phage therapy through synthetic biology and genome engineering. Curr Opin Biotechnol. 2021 Apr;68:151-159. doi: 10.1016/j.copbio.2020.11.003. Epub 2020 Dec 10.