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

• ClinicalTrials.gov Identifier: NCT04191148
• Recruitment Status: Completed
• First Posted: December 9, 2019
• Results First Posted: March 16, 2022
• Last Update Posted: March 16, 2022
• Sponsor: Locus Biosciences
• Information provided by (Responsible Party): Locus Biosciences

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Urinary Tract Infections	Drug: LBP-EC01; Drug: Placebo	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• 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
• Primary Purpose: Basic Science
• 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
• Actual Study Start Date: December 30, 2019
• Actual Primary Completion Date: November 19, 2020
• Actual Study Completion Date: November 19, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: LBP-EC01; crPhage cocktail	Drug: LBP-EC01; crPhage cocktail: at approximately 1.5 x 10^10 to 3.0 x 10^10 PFU/vial dosed BID by intraurethral administration
Placebo Comparator: Placebo; Lactated Ringer's solution, injection, USP	Drug: Placebo; Lactated Ringers Solution for Injection dosed BID by intraurethral administration

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment-related Adverse Events as Assessed by DAIDS v2.1 [ Time Frame: 35 days ]
   Safety and tolerability of LBP-EC01: Number of participants with treatment-related adverse events as assessed by DAIDS v2.1
2. Pharmacokinetics of LBP-EC01: Cmax [ Time Frame: 28 days ]
   Maximum concentration determined directly from the concentration-time profile
3. Pharmacokinetics of LBP-EC01: Tmax [ Time Frame: 28 days ]
   Time to maximum concentration
4. Pharmacokinetics of LBP-EC01: AUC [ Time Frame: 28 days ]
   Area under the concentration versus time curve from time 0 to the last measurable concentration

Secondary Outcome Measures :

1. 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 [ Time Frame: 28 days ]
   The secondary objective of this study was to evaluate the pharmacodynamics (PD) of LBP-EC01 through reduction in urinary E.coli burden as defined by at least 1 log CFU reduction from baseline.
2. Time to 1 Logarithmic Reduction in Urinary E.Coli Count From Baseline [ Time Frame: 28 days ]
   The secondary objective of this study was to evaluate the pharmacodynamics (PD) of LBP-EC01 through time to 1 logarithmic reduction in urinary E.coli count from baseline
3. Recurrence of E.Coli Colonization or Incidence of Infection Based on Clinical Signs and Symptoms [ Time Frame: 28 days ]
   The secondary objective of this study was to evaluate the pharmacodynamics (PD) of LBP-EC01 through recurrence of E.Coli colonization or incidence of infection based on clinical signs and symptoms
4. Changes in Immunoglobulin (Ig)A [ Time Frame: 28 days ]
   The secondary objective of this study was to evaluate the pharmacodynamics (PD) of LBP-EC01 through changes in IgA
5. Changes in IgE [ Time Frame: 28 days ]
   The secondary objective of this study was to evaluate the pharmacodynamics (PD) of LBP-EC01 through changes in IgE with a positive detection of >100 IU/mL
6. Changes in IgG [ Time Frame: 28 days ]
   The secondary objective of this study was to evaluate the pharmacodynamics (PD) of LBP-EC01 through changes in IgG with a positive detection of >1600 mg/dL (>16.0 g/L)
7. Changes in IgM [ Time Frame: 28 days ]
   The secondary objective of this study was to evaluate the pharmacodynamics (PD) of LBP-EC01 through changes in IgM with a positive detection >230 mg/dL (>2.3 g/L)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Alabama

Pinnacle Research Group

Anniston, Alabama, United States, 36207

United States, California

Tilda Research

Irvine, California, United States, 92612

United States, Florida

Universal Axon Clinical Research

Doral, Florida, United States, 33166

Universal Axon - Homestead, LL

Homestead, Florida, United States, 33030

AMPM Research Clinic

Miami Gardens, Florida, United States, 33169

Innovation Medical Research Center

Palmetto Bay, Florida, United States, 45209

United States, South Carolina

Ralph H. Johnson VA Medical Center

Charleston, South Carolina, United States, 29401

Sponsors and Collaborators

Locus Biosciences

  Study Documents (Full-Text)

Documents provided by Locus Biosciences:

Study Protocol  [PDF] October 1, 2020

Statistical Analysis Plan  [PDF] December 17, 2020

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Locus Biosciences
• ClinicalTrials.gov Identifier: NCT04191148
• Other Study ID Numbers: LBx-1001
• First Posted: December 9, 2019
• Results First Posted: March 16, 2022
• Last Update Posted: March 16, 2022
• Last Verified: November 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Locus Biosciences:

UTI; Bacteriophage; Phage

Additional relevant MeSH terms:

Urinary Tract Infections; Infections; Urologic Diseases