LBP-EC01 for Urinary Tract Infection

(ELIMINATE Trial)

Recruiting at 26 trial locations

Overseen By Locus Clinical Operations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Locus Biosciences

Must not be taking: Antibacterials, Investigational drugs

Disqualifiers: Systemic illness, Diabetes, Immunocompromised, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

318 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called LBP-EC01, which uses a special mix of bacteriophages (viruses that target bacteria) to treat urinary tract infections (UTIs) caused by E. coli bacteria. The researchers aim to determine if LBP-EC01 combined with antibiotics is more effective than antibiotics alone. Individuals who have experienced UTIs in the past year due to E. coli and currently have symptoms like painful urination or frequent urges to urinate might be suitable candidates. Participants will be randomly assigned to receive either the new treatment or a placebo, alongside standard antibiotics. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires participants to stop taking continuous low dose antimicrobial prophylaxis and not use any medication for treating the current UTI for the first 10 days of the study. However, postmenopausal women can continue vaginal estrogen therapy if it has been stable for over 3 months.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that LBP-EC01, a treatment being tested for urinary tract infections (UTIs), was safe in earlier studies. These studies found that LBP-EC01 was well-tolerated by patients, with no major safety issues reported. This is encouraging for those considering joining the trial.

LBP-EC01 is a mix of special viruses called bacteriophages. These viruses specifically attack and kill bacteria, offering a new way to treat infections. In past trials, patients did not experience severe or unexpected side effects, suggesting that this treatment might be safe for people with UTIs caused by E. coli bacteria.

These results indicate that LBP-EC01 has a good safety record, but discussing any concerns or questions with the trial team before participating is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for UTI?

Researchers are excited about LBP-EC01 for urinary tract infections (UTIs) because it targets bacteria in a novel way. Unlike traditional antibiotics, which kill bacteria indiscriminately, LBP-EC01 uses a virus called a bacteriophage, specifically designed to infect and eliminate harmful E. coli bacteria while sparing beneficial bacteria. Additionally, LBP-EC01 is administered both intraurethrally and intravenously, allowing it to act directly at the site of infection and systemically, potentially leading to faster and more effective treatment outcomes. This targeted approach could reduce the risk of antibiotic resistance, a major issue with current UTI treatments.

What evidence suggests that this trial's treatments could be effective for urinary tract infections?

Research has shown that LBP-EC01, a mix of viruses that attack bacteria, may help treat urinary tract infections (UTIs) caused by E. coli. This trial will evaluate LBP-EC01 in various treatment arms, administering it with antibiotics like TMP/SMX. Studies have found that LBP-EC01 can effectively reach the bladder, which is crucial for fighting the infection. Additionally, early tests showed positive results when LBP-EC01 was used with antibiotics, leading to better outcomes than antibiotics alone. These findings suggest that LBP-EC01 could effectively treat UTIs, especially those that recur. ^{1 2 3 4 6}

Who Is on the Research Team?

Paul Kim

Principal Investigator

Locus Biosciences

Are You a Good Fit for This Trial?

This trial is for people who've had at least 2 UTIs in the past 6 months or 3 in the last year, with one caused by E. coli. They must have current symptoms of a UTI and not be using certain products like cranberry or probiotics. Sexually active women must use contraception, and participants can't take other UTI medications for the first 10 days.

Inclusion Criteria

I have a UTI with pain, frequent or urgent urination, and my tests show infection.

I am using effective birth control and will continue for 2 weeks after my last treatment.

I have signs of a UTI and my urine tests show infection.

Exclusion Criteria

Patients who reside in a long-term care facility.

I have had symptoms for more than a week.

I haven't taken antibiotics for UTI in the last 3 days, unless they didn't work and my symptoms continued.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Regimen Selection

An open-label, 30 patient, 3-arm PK assessment to evaluate optimal dosing regimen

5 days

Daily visits (in-person)

Efficacy, Safety, Tolerability and Pharmacokinetics

A blinded, 288 patient, 1:1 randomized evaluation of the selected dose regimen versus placebo

21 days

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• LBP-EC01
• TMP/SMX

Trial Overview The ELIMINATE Trial is testing LBP-EC01, a bacteriophage cocktail against drug-resistant E. coli causing UTIs. It's compared to placebo alongside antibiotics in patients with recurrent infections to find an optimal dose and assess effectiveness.

How Is the Trial Designed?

Group I: Part 2: LBP-EC01 Experimental Treatment 2 Interventions

LBP-EC01 given by dose regimen selected from Part 1. IU LBP-EC01 on D1 and D2 with IV LBP-EC01 (1x10\^11 PFU) and oral TMP/SMX on D1 through D3.

Group II: Part 1- Arm 6 (previously 3) Experimental Treatment 2 Interventions

Intraurethral (IU) LBP-EC01 on D1 and D2 with intravenous (IV) LBP-EC01 infusion (1x10\^12 PFU) and oral TMP/SMX on D1 through D3.

Group III: Part 1- Arm 5 (previously 2) Experimental Treatment 2 Interventions

Intraurethral (IU) LBP-EC01 on D1 and D2 with intravenous (IV) LBP-EC01 (1x10\^10 PFU) and oral TMP/SMX on D1 through D3.

Group IV: Part 1- Arm 4 (previously 1) Experimental Treatment 2 Interventions

Intraurethral (IU) LBP-EC01 on D1 and D2 with intravenous (IV) LBP-EC01 (1x10\^11 PFU) and oral TMP/SMX on D1 through D3.

Group V: Part 2: Placebo Placebo Group 2 Interventions

Placebo given by dose regimen selected from Part 1. IU placebo on D1 and D2 with IV placebo and oral TMP/SMX on D1 through D3.

Who Is Running the Clinical Trial?

Locus Biosciences

Lead Sponsor

Trials

2

Recruited

350+

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

In a study involving 26 young women, neither trimethoprim (TMP) alone nor the combination with sulfamethoxazole (TMP-SMX) led to the development of resistant bacterial strains in fecal or introital floras after treatment for urinary tract infections.

Both TMP and TMP-SMX effectively cleared Enterobacteriaceae from the introitus and rectal areas, and adequate concentrations of TMP were found in vaginal secretions to inhibit most E. coli strains responsible for urinary tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of trimethoprim and trimethoprim-sulfamethoxazole on development of drug-resistant vaginal and fecal floras. Pancoast, SJ., Hyams, DM., Neu, HC.[2021]

In a study of 6162 outpatients, those receiving high-dose trimethoprim-sulfamethoxazole (TMP-SMX) had a significantly higher incidence of hyperkalemia (3.06% vs 1.05%) and acute renal injury (1.99% vs 0.70%) compared to those on low-dose TMP-SMX.

Key risk factors for hyperkalemia and acute renal injury included older age, use of NSAIDs or ACE inhibitors, and elevated baseline serum creatinine, highlighting the need for careful monitoring of potassium and kidney function in patients prescribed high-dose TMP-SMX.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of hyperkalemia and serum creatinine elevation associated with different dosage levels of outpatient trimethoprim-sulfamethoxazole with and without concomitant medications. Gentry, CA., Nguyen, AT.[2015]

In a study involving 32 women and 6 preadolescents, thrice-weekly treatment with trimethoprim-sulfamethoxazole for six months effectively reduced the incidence of recurrent urinary tract infections to 0.1 infections per patient-year.

The prophylactic treatment did not lead to increased colonization or infection with trimethoprim-resistant bacteria, although some patients experienced recurrence of infections after stopping the treatment, with a mean time to recurrence of 2.6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylaxis of recurrent urinary tract infection in female patients. Efficacy of low-dose, thrice-weekly therapy with trimethoprim-sulfamethoxazole. Harding, GK., Buckwold, FJ., Marrie, TJ., et al.[2016]

Trimethoprim-sulfamethoxazole (TMP-SMX) significantly reduces the occurrence of bacteriuria and symptomatic urinary tract infections in individuals with recent spinal cord injuries during the first 4 months of intermittent catheterization, as shown in a study of 129 adults.

Despite its efficacy, TMP-SMX is associated with common adverse reactions, and a high proportion of bacteriuria episodes were caused by TMP-SMX-resistant organisms, which may limit its effectiveness in long-term use, especially in institutional settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylaxis of urinary tract infection in persons with recent spinal cord injury: a prospective, randomized, double-blind, placebo-controlled study of trimethoprim-sulfamethoxazole. Gribble, MJ., Puterman, ML.[2019]

In a study of 403 women with uncomplicated pyelonephritis, the resistance rate of E. coli to trimethoprim-sulfamethoxazole (TMP-SMX) was found to be 24%, indicating a significant prevalence of resistance in many areas of the U.S.

Despite the resistance to TMP-SMX, fluoroquinolone resistance rates were low (1% for ciprofloxacin and 3% for levofloxacin), suggesting that fluoroquinolones remain the preferred treatment for uncomplicated pyelonephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and risk factor analysis of trimethoprim-sulfamethoxazole- and fluoroquinolone-resistant Escherichia coli infection among emergency department patients with pyelonephritis. Talan, DA., Krishnadasan, A., Abrahamian, FM., et al.[2022]

In a study of healthy nonpregnant premenopausal women with uncomplicated urinary tract infections (UTIs), trimethoprim-sulfamethoxazole (TMP-SMX) was effective in treating infections caused by TMP-SMX-susceptible pathogens, achieving a microbiological cure in 86% of those cases.

However, for infections caused by TMP-SMX-resistant pathogens, only 42% achieved microbiological cure, indicating that TMP-SMX is not effective for these resistant infections and should not be the first choice treatment in areas with high resistance rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empiric use of trimethoprim-sulfamethoxazole (TMP-SMX) in the treatment of women with uncomplicated urinary tract infections, in a geographical area with a high prevalence of TMP-SMX-resistant uropathogens. Raz, R., Chazan, B., Kennes, Y., et al.[2022]

In a study involving 52 patients, the combination of trimethoprim and sulfamethoxazole effectively treated urinary tract infections, showing a strong correlation between in vitro sensitivity and clinical response.

This drug combination was particularly effective against certain bacterial strains that were resistant to commonly used antibiotics, highlighting its potential as a valuable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The combination of trimethoprim and sulfamethoxazole in the treatment of urinary tract infection. Crichton, EP., McDonnell, CE.[2018]

In a study of 40 patients with urinary tract infections, the combination of trimethoprim and sulfamethoxazole was effective, achieving sterile urine in 100% of patients with uncomplicated infections after 3 days and 89% after 14 days.

The treatment showed a synergistic effect against 55% of bacterial strains tested, including some that were resistant to sulfamethoxazole, although side effects were reported in 3 patients, leading to treatment withdrawal in 2 cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term treatment of urinary tract infections with trimethoprim/sulphamethoxazole: a clinical and bacteriological study. Nielsen, ML., Laursen, H., Strøyer, I.[2015]

A rare adverse reaction to trimethoprim-sulfamethoxazole (TMP-SMX) was observed in a healthy adolescent, who experienced severe mental status changes and hallucinations after just three doses of the medication.

The patient's symptoms improved significantly after stopping TMP-SMX, highlighting the importance of monitoring for unusual side effects even in otherwise healthy individuals when using this commonly prescribed antibiotic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transient psychosis in an immune-competent patient after oral trimethoprim-sulfamethoxazole administration. Saidinejad, M., Ewald, MB., Shannon, MW.[2015]

In a study of 22 adults with serious gram-negative bacterial infections, intravenous trimethoprim-sulfamethoxazole (TMP-SMZ) demonstrated a cure rate of 63% and improvement in 21% of patients, indicating its efficacy in treating severe infections.

While mild adverse reactions were common, including skin rashes and transient declines in renal and hepatic function, the only serious side effect was an acute reaction in one patient, suggesting that TMP-SMZ can be a safe option for life-threatening infections resistant to other antibiotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of intravenous trimethoprim-sulfamethoxazole for serious infections. Schmidt, U., Sen, P., Kapila, R., et al.[2019]

An 82-year-old woman experienced significant hyponatremia (low sodium levels) after taking trimethoprim-sulfamethoxazole (TMP-SMX) for a urinary tract infection, with sodium dropping from 132 mmol/L to 121 mmol/L after treatment.

Rechallenging the patient with TMP-SMX led to another decrease in sodium levels, confirming the drug's role in causing hyponatremia, which, while rare, is a potentially serious side effect that healthcare providers should monitor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyponatremia after initiation and rechallenge with trimethoprim-sulfamethoxazole in an older adult. Huntsberry, AM., Linnebur, SA., Vejar, M.[2018]

In a study of 283 female patients with urinary tract infections (UTIs), resistance to trimethoprim/sulfamethoxazole (TMP/SMX) was found to be 18%, which is just below the 20% threshold recommended by the Infectious Disease Society of America for continued use as an empiric treatment.

Fluoroquinolone resistance was very low at only 1.5%, and overall resistance rates to other narrow-spectrum agents like nitrofurantoin (5%) and cefazolin (4%) were lower than published antibiograms, suggesting that these agents remain effective options for treating UTIs in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimicrobial resistance in uncomplicated urinary tract infections in 3 California EDs. Moffett, SE., Frazee, BW., Stein, JC., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39134085/

the randomised, open-label, first part of a ... The primary outcome was the level of LBP-EC01 in urine and blood across the treatment period and over 48 h after the last dose and was ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1473309924004249

Safety, pharmacokinetics, and pharmacodynamics of LBP ... The primary endpoint for part 1, pharmacokinetic verification that high levels of LBP-EC01 could be delivered to the bladder, was achieved. ... Urinary tract ...

3. locus-bio.com locus-bio.com/locus-biosciences-announces-positive-results-from-part-1-of-eliminate-phase-2-trial-of-the-engineered-bacteriophage-therapy-lbp-ec01-published-in-the-lancet-infectious-diseases/

Locus Biosciences This Phase 2 trial is evaluating LBP-EC01, a CRISPR-Cas3 genetically engineered bacteriophage therapy designed to treat patients with uncomplicated urinary ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05488340

NCT05488340 | A Study of LBP-EC01 in the Treatment ... The efficacy of LBP-EC01 when used concomitantly with TMP/SMX compared to placebo when used concomitantly with TMP/SMX on resolution of acute uUTI clinical ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04191148

NCT04191148 | Safety, Tolerability, and PK of LBP-EC01 ... Study LBx-1001 is a multi-center randomized, double-blind study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ...

6. crisprmedicinenews.com crisprmedicinenews.com/news/locus-biosciences-shares-positive-phase-2-data-for-crispr-edited-phage-treatment-for-urinary-tract-i/

Locus Biosciences Shares Positive Phase 2 Data for ... LBP-EC01 is being developed as a novel treatment for uncomplicated urinary tract infections caused by antimicrobial-resistant and multi-drug-resistant E. coli.