Urinary Tract InfectionsPhase 1NCT04191148
Safety, Tolerability, and PK of LBP-EC01 in Patients With Lower Urinary Tract Colonization Caused by E. Coli
A Phase 1 study testing LBP-EC01 in people with Urinary Tract Infections, run by Locus Biosciences at 7 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urinary Tract Infections
- What is being tested?
- LBP-EC01
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 7 sitesUnited States
- Study dates
- 30 Dec 2019to 19 Nov 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Pinnacle Research Group
Anniston, Alabama, 36207
Ralph H. Johnson VA Medical Center
Charleston, South Carolina, 29401
Universal Axon Clinical Research
Doral, Florida, 33166
Universal Axon - Homestead, LL
Homestead, Florida, 33030
Tilda Research
Irvine, California, 92612
AMPM Research Clinic
Miami Gardens, Florida, 33169
Innovation Medical Research Center
Palmetto Bay, Florida, 45209
About this study
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
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.
Read the 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.
- Conditions
- Urinary Tract Infections
- Being tested
- LBP-EC01, Placebo
- Keywords
- UTI, Bacteriophage, Phage
- Medical subject headings
- Urinary Tract Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LBP-EC01Drug
crPhage cocktail: at approximately 1.5 x 10^10 to 3.0 x 10^10 PFU/vial dosed BID by intraurethral administration
PlaceboDrug
Lactated Ringers Solution for Injection dosed BID by intraurethral administration
| Study group | Role | What they receive |
|---|---|---|
| LBP-EC01 | Experimental | crPhage cocktail Receives: Drug: LBP-EC01 |
| Placebo | Placebo comparator | Lactated Ringer's solution, injection, USP Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 35 days
Pharmacokinetics of LBP-EC01: Cmax
Maximum concentration determined directly from the concentration-time profile
Measured: 28 days
Pharmacokinetics of LBP-EC01: Tmax
Time to maximum concentration
Measured: 28 days
Pharmacokinetics of LBP-EC01: AUC
Area under the concentration versus time curve from time 0 to the last measurable concentration
Measured: 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
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.
Measured: 28 days
Time to 1 Logarithmic Reduction in Urinary E.Coli Count From Baseline
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
Measured: 28 days
Recurrence of E.Coli Colonization or Incidence of Infection Based on Clinical Signs and Symptoms
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
Measured: 28 days
Changes in Immunoglobulin (Ig)A
The secondary objective of this study was to evaluate the pharmacodynamics (PD) of LBP-EC01 through changes in IgA
Measured: 28 days
Changes in IgE
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
Measured: 28 days
Changes in IgG
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)
Measured: 28 days
Changes in IgM
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)
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2019
- Study start30 Dec 2019
- Primary completion19 Nov 2020
- Study completion19 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Urinary Tract InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 2:1 randomized, placebo controlled, blinded study
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Locus Biosciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04191148
- Sponsor's protocol ID
- LBx-1001
- Status last verified
- Nov 2021
- First submitted
- 4 Dec 2019
- Last updated
- 16 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 33310655
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04191148
- Acronym / sponsor ID
- LBx-1001
- Conditions
- Urinary Tract Infections
- Keywords
- UTI, Bacteriophage, Phage
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Locus BiosciencesIndustry (pharma, biotech, devices)
- Study start
- 30 Dec 2019 (actual)
- Primary completion
- 19 Nov 2020 (actual)
- Study completion
- 19 Nov 2020 (actual)
- First posted
- 9 Dec 2019 (actual)
- Results
- Posted 16 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- 2:1 randomized, placebo controlled, blinded study
| Arm | Type | Receives |
|---|---|---|
| LBP-EC01 | Experimental | Drug: LBP-EC01crPhage cocktail |
| Placebo | Placebo comparator | Drug: PlaceboLactated Ringer's solution, injection, USP |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- Patients must have experience with urinary catheterization or have Medical Monitor approval if the patient does not have prior experience with catheterization.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LBP-EC01crPhage cocktail: at approximately 1.5 x 10^10 to 3.0 x 10^10 PFU/vial dosed BID by intraurethral administration | Drug | LBP-EC01 |
| PlaceboLactated Ringers Solution for Injection dosed BID by intraurethral administration | Drug | Placebo |
Primary outcome
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
Pharmacokinetics of LBP-EC01: Cmax
Time frame: 28 days
Maximum concentration determined directly from the concentration-time profile
Pharmacokinetics of LBP-EC01: Tmax
Time frame: 28 days
Time to maximum concentration
Pharmacokinetics of LBP-EC01: AUC
Time frame: 28 days
Area under the concentration versus time curve from time 0 to the last measurable concentration
7 secondary outcomes
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
Time to 1 Logarithmic Reduction in Urinary E.Coli Count From Baseline
Time frame: 28 days
Recurrence of E.Coli Colonization or Incidence of Infection Based on Clinical Signs and Symptoms
Time frame: 28 days
Changes in Immunoglobulin (Ig)A
Time frame: 28 days
Changes in IgE
Time frame: 28 days
Changes in IgG
Time frame: 28 days
Changes in IgM
Time frame: 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33310655Lenneman 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LBP-EC01 in people with Urinary Tract Infections, run by Locus Biosciences at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-related Adverse Events as Assessed by DAIDS v2.1 (time frame: 35 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04191148, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2022.