This is a Phase 2 superiority study of LBP-EC01, a recombinant bacteriophage cocktail, with an initial open-label 3-arm pharmacokinetic (PK) lead-in portion of 30 patients to evaluate the optimal dosing regimen to be used in the subsequent 288 patient blinded portion of the study which will be randomized 1:1 comparing LBP-EC01 + antibiotic versus placebo + antibiotic in patients with a history of prior urinary tract infection (UTI) cased by E. coli. All patients will be required to have an active acute uncomplicated UTI at baseline.
This study will consist of two parts. Part 1 - Dose regimen selection: An open-label, 30 patient, 3-arm PK assessment of: Arm 4 (previously 1): LBP-EC01 (approximately 2×10\^12 PFU) given by IU administration on D1 and D2 and LBP-EC01 (approximately 1×10\^11 PFU) IV given as a 1 milliliter (mL) bolus QD from D1 through D3 concomitantly with oral trimethoprim/sulfamethoxazole (TMP 160mg/SMX 800mg) BID from D1 through D3 (6 doses); Arm 5 (previously 2): LBP-EC01 (approximately 2×10\^12 PFU) given by IU administration on D1 and D2 and LBP-EC01 (approximately 1×10\^10 PFU) IV given as a 1 mL bolus QD from D1 through D3 concomitantly with oral TMP/SMX BID from D1 through D3 (6 doses); Arm 6 (previously 3): LBP-EC01 (2×10\^12 PFU) given by IU administration on D1 and D2 and LBP-EC01 (approximately 1×10\^12 PFU) IV given as a 100 mL IV infusion over 2 h on D1 through D3 concomitantly with oral TMP/SMX BID from D1 through D3 (6 doses). Part 2 - Efficacy, Safety, Tolerability and Pharmacokinetics: A blinded, 288 patient, 1:1 randomized evaluation of the Arm 4 dose regimen, selected from Part 1, versus placebo + antibiotic (TMP/SMX -160 mg TMP and 800 mg SMX) given orally BID on Days 1 through 3.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
318
Intraurethral (IU) dose of two (2) x 6mL vials of LBP-EC01 (approximately 2x10\^12 PFU) diluted in 188 mL of Lactated Ringer's solution on Day 1 and Day 2. Intravenous (IV) dose of 0.6mL of LBP-EC01 (approximately 1x10\^11 PFU) diluted in 0.4mL of Lactated Ringer's solution given on Days 1 through Day 3.
Intraurethral (IU) dose of two (2) x 6mL vials of LBP-EC01 (approximately 2x10\^12 PFU) diluted in 188 mL of Lactated Ringer's solution on Day 1 and Day 2. Intravenous (IV) dose of 0.06 mL of LBP-EC01 (approximately 1x10\^10 PFU) diluted in 0.94 mL of Lactated Ringer's solution given on Days 1 through Day 3.
Intraurethral (IU) dose of two (2) x 6mL vials of LBP-EC01 (approximately 2x10\^12 PFU) diluted in 188 mL of Lactated Ringer's solution on Day 1 and Day 2. Intravenous infusion dose of 6mL of LBP-EC01 (approximately 1x10\^12 PFU) diluted in 94 mL of Lactated Ringer's solution given over 2 hours on Days 1 through Day 3.
Dose regimen selected from Part 1 of placebo (Tris buffer).
Dose regimen selected from Part 1 of LBP-EC01 (1x10\^10 - 1x10\^13 PFU) per dose.
TMP/SMX (160 mg trimethoprim and 800 mg sulfamethoxazole) given orally BID on Days 1 through 3.
Research Site 138
Fresno, California, United States
COMPLETEDResearch Site 131
Lancaster, California, United States
RECRUITINGResearch Site 123
Los Angeles, California, United States
RECRUITINGResearch Site 125
Montebello, California, United States
RECRUITINGResearch Site 137
San Diego, California, United States
RECRUITINGResearch Site 126
Tustin, California, United States
RECRUITINGResearch Site 102
Doral, Florida, United States
RECRUITINGResearch Site 140
Jensen Beach, Florida, United States
COMPLETEDResearch Site 103
Miami, Florida, United States
RECRUITINGResearch Site 149
Miami, Florida, United States
RECRUITING...and 2 more locations
Part 1: Levels of LBP-EC01 in urine and blood measured by quantitative plaquing assay across the treatment period and over 48 h after the last dose
The regimen for LBP-EC01 when used concomitantly with TMP/SMX which optimizes pharmacokinetics (PK) for LBP-EC01 will be selected.
Time frame: Day 1 to Day 5
Part 2: Proportion of patients with resolution of clinical symptoms and microbiologic response of uUTI caused by drug resistant E. coli as defined at Day 10 test of cure (TOC).
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 symptoms and demonstration of microbiologic response (CCMR) of acute uUTI caused by drug resistant E. coli will be assessed.
Time frame: Day 10
Part 1: Number of patients with Adverse Events (AEs) and Serious Adverse Events (SAEs)
The safety and tolerability of LBP-EC01 when given with TMP/SMX will be assessed.
Time frame: Day 1 to Day 34
Part 1: Number of patients with immunogenicity
The immunogenicity of LBP-EC01 by measuring neutralizing antibody (NAb) levels will be assessed.
Time frame: Baseline Day 1 to Day 2, Day 5, Day 10, Day 34/Early Termination [ET]) post-hoc
Part 2: Proportion of patients with antimicrobial drug resistant (AMR) E. coli achieving maintenance of combined clinical and microbiologic response (CCMR) at Day 21.
The impact of LBP-EC01 when used concomitantly with TMP/SMX compared to placebo when used concomitantly with TMP/SMX on maintenance of CCMR success in those randomized patients with AMR E. coli uUTI demonstrating an initial response will be assessed.
Time frame: Day 21
Part 2: Proportion of patients with CCMR of uUTI caused by E. coli at Day 10/TOC.
The efficacy of LBP-EC01 when used concomitantly with TMP/SMX compared to placebo when used concomitantly with TMP/SMX, on CCMR of uUTI caused by E. coli (irrespective of drug resistant status) will be assessed.
Time frame: Day 10
Part 2: Proportion of patients with CCMR of uUTI caused by multi-drug resistant (MDR) E. coli at Day 10/TOC.
The impact of LBP-EC01 when used concomitantly with TMP/SMX compared to placebo when used concomitantly with TMP/SMX on CCMR in patients with uUTI caused by MDR E. coli at Day 10/TOC.
Time frame: Day 21
Part 2: Proportion of patients with MDR E. coli achieving maintenance of CCMR at Day 21.
The impact of LBP-EC01 when used concomitantly with TMP/SMX compared to placebo when used concomitantly with TMP/SMX on the maintenance of CCMR in patients with uUTI caused by MDR E. coli at Day 21.
Time frame: Within the 6-month follow-up period
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.