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

NCT04191148 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: LBx-1001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 7

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.

Conditions

Urinary Tract Infections

Keywords

UTI; Bacteriophage; Phage

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Treatment-related Adverse Events as Assessed by DAIDS v2.1

  Safety and tolerability of LBP-EC01: Number of participants with treatment-related adverse events as assessed by DAIDS v2.1

  35 days

• Pharmacokinetics of LBP-EC01: Cmax

  Maximum concentration determined directly from the concentration-time profile

  28 days

• Pharmacokinetics of LBP-EC01: Tmax

  Time to maximum concentration

  28 days

• Pharmacokinetics of LBP-EC01: AUC

  Area under the concentration versus time curve from time 0 to the last measurable concentration

  28 days

Secondary Outcomes (7)

• 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

  28 days

• Time to 1 Logarithmic Reduction in Urinary E.Coli Count From Baseline

  28 days

• Recurrence of E.Coli Colonization or Incidence of Infection Based on Clinical Signs and Symptoms

  28 days

• Changes in Immunoglobulin (Ig)A

  28 days

• Changes in IgE

  28 days

Study Arms (2)

LBP-EC01

EXPERIMENTAL

crPhage cocktail

Drug: LBP-EC01

Placebo

PLACEBO COMPARATOR

Lactated Ringer's solution, injection, USP

Drug: Placebo

Interventions

LBP-EC01 DRUG

crPhage cocktail: at approximately 1.5 x 10\^10 to 3.0 x 10\^10 PFU/vial dosed BID by intraurethral administration

LBP-EC01

Placebo DRUG

Lactated Ringers Solution for Injection dosed BID by intraurethral administration

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Males or females 18 years of age or older.
• 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
• Patients must have experience with urinary catheterization or have Medical Monitor approval if the patient does not have prior experience with catheterization.
• In good general health as evidenced by medical history and physical examination.
• 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.

You may not qualify if:

• 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.
• 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.
• Presence of a surgically-modified bladder, except for a repaired ruptured bladder.
• 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.
• Active severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, or neurologic disease per the investigator's discretion.
• Any malignancies within the past 5 years (except those in remission).
• Unless deemed acceptable by the Investigator, prescription drugs, over-the-counter (OTC) medications and supplements that acidify the urine are excluded.
• Patients who have had allergic reactions to similar compounds, or any excipients.
• Participation in an investigational drug or device study within 1 month (or 7 half-lives of drug, whichever is longer) prior to randomization.
• 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.

Sponsors & Collaborators

• Locus Biosciences: lead

Study Sites (7)

Pinnacle Research Group

Anniston, Alabama, 36207, United States

Location

Tilda Research

Irvine, California, 92612, United States

Location

Universal Axon Clinical Research

Doral, Florida, 33166, United States

Location

Universal Axon - Homestead, LL

Homestead, Florida, 33030, United States

Location

AMPM Research Clinic

Miami Gardens, Florida, 33169, United States

Location

Innovation Medical Research Center

Palmetto Bay, Florida, 45209, United States

Location

Ralph H. Johnson VA Medical Center

Charleston, South Carolina, 29401, United States

Location

Related Publications (1)

• 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.

  PMID: 33310655 DERIVED

MeSH Terms

Conditions

Urinary Tract Infections

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Clinical Trial Manager
• Organization: Medpace

E.Plummer@Medpace.com

513-630-0130

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double blind
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 2:1 randomized, placebo controlled, blinded study

Study Record Dates

• First Submitted: December 4, 2019
• First Posted: December 9, 2019
• Study Start: December 30, 2019
• Primary Completion: November 19, 2020
• Study Completion: November 19, 2020
• Last Updated: March 16, 2022
• Results First Posted: March 16, 2022

Record last verified: 2021-11

Locations

US (7)