Safety, Tolerability, and PK of LBP-EC01 in Patients With Lower Urinary Tract Colonization Caused by E. Coli
Condition: Urinary Tract Infections
MeSH terms: Urinary Tract Infections
Intervention: LBP-EC01; Placebo
Intervention description: crPhage cocktail: at approximately 1.5 x 10^10 to 3.0 x 10^10 PFU/vial dosed BID by intraurethral administration; Lactated Ringers Solution for Injection dosed BID by intraurethral administration
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 2:1 randomized, placebo controlled, blinded study
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Double blind
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: UTI; Bacteriophage; Phage

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.
    

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.