LBP-EC01 for Urinary Tract Infection

(ELIMINATE Trial)

Recruiting at37 trial locations

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Locus Biosciences

Must not be taking: Antibacterials, Investigational drugs

Disqualifiers: Systemic illness, Diabetes, Immunocompromised, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing LBP-EC01, a virus mixture that targets E. coli bacteria, in patients with recurring UTIs caused by E. coli. The study aims to find the best dose and compare its effectiveness and safety with standard antibiotic treatment.

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.

What data supports the effectiveness of the drug LBP-EC01, which includes trimethoprim-sulfamethoxazole, for treating urinary tract infections?

Research shows that trimethoprim-sulfamethoxazole is effective in treating urinary tract infections, with high rates of success in clearing infections in patients. It has been used successfully for both short-term treatment and long-term prevention of recurrent infections. ^{1 2 3 4 5}

Is LBP-EC01 (also known as TMP-SMX, Septra, Bactrim) generally safe for humans?

TMP-SMX is generally well tolerated, but it can cause some side effects like skin rashes, changes in kidney and liver function, and rare cases of mental confusion or hallucinations. Serious side effects are uncommon, but mild reactions like skin rashes and temporary changes in kidney or liver function have been reported. ^{1 6 7 8 9}

How is the drug LBP-EC01 for urinary tract infections different from other treatments?

LBP-EC01 is unique because it combines trimethoprim-sulfamethoxazole (TMP-SMX), a common antibiotic for UTIs, with another component, potentially offering a novel approach to treatment. However, resistance to TMP-SMX is a concern, and its effectiveness may vary depending on local resistance patterns. ^{1 4 10 11 12}

Research Team

Paul Kim

Principal Investigator

Locus Biosciences

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• LBP-EC01 (Virus Therapy)
• TMP/SMX (Antibiotic)

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.

Participant Groups

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

Findings from Research

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 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]

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 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 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]

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 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 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]

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 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]

References

1. United States 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. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Short-term treatment of urinary tract infections with trimethoprim/sulphamethoxazole: a clinical and bacteriological study. [2015]

3. Canada pubmed.ncbi.nlm.nih.gov

The combination of trimethoprim and sulfamethoxazole in the treatment of urinary tract infection. [2018]

4. United States 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Prophylaxis of recurrent urinary tract infection in female patients. Efficacy of low-dose, thrice-weekly therapy with trimethoprim-sulfamethoxazole. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Transient psychosis in an immune-competent patient after oral trimethoprim-sulfamethoxazole administration. [2015]

7. United States 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. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Clinical evaluation of intravenous trimethoprim-sulfamethoxazole for serious infections. [2019]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Hyponatremia after initiation and rechallenge with trimethoprim-sulfamethoxazole in an older adult. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Antimicrobial resistance in uncomplicated urinary tract infections in 3 California EDs. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Effect of trimethoprim and trimethoprim-sulfamethoxazole on development of drug-resistant vaginal and fecal floras. [2021]

12. United States 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. [2022]