Back to resultsA Phase 2a Study, Effect of Vancomycin With vs Without Delpazolid (LCB01-0371) in Patients With MRSA Bacteremia
Primary Purpose
MRSA Bacteremia
Status
Recruiting
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Delpazolid
Vancomycin
Placebo of Delpazolid
Sponsored by
About this trial
This is an interventional treatment trial for MRSA Bacteremia focused on measuring MRSA, Staphylococcus aureus bacteremia, SAB, bloodstream infection, BSI, Bacteremia
Eligibility Criteria
Inclusion Criteria:
- Male or female ≥19 years of age on the date of written consent
- Subject who has confirmed positive MRSA at least one set of blood cultures within 72 hours prior to randomization OR, Subject who has confirmed positive MRSA at least one set of blood culture whthin 96 hours prior to randomization and treated with vancomycin at least 72 hours prior to randomization
- Subject who has clinical symptoms or signs of MRSA bacteremia according to the judgment of the investigator
- Subject who voluntarily decides to participate in this clinical trial after being explained fully, and agrees in writing to implement the clinical trial compliance matters
Exclusion Criteria:
- Subject with polymicrobial bacteremia or infections including Gram-negative strain
- Subject undergoing or in need of treatment with antiviral or antifungal drugs
- Subject who has received treatment for MRSA bacteremia within 3 months of screening
- Subject who has been administered effective antibiotics against MRSA (Vancomycin, etc.) for more than 96 hours prior to the first investigational product administration. (However, antibiotics effective for MRSA such as vancomycin are allowed to be administered for less than 72 hours.)
- Septic shock patients
- Subject who has hypersensitivity to vancomycin or linezolid
- Subject who has a history of hypersensitivity to peptide-based antibiotics and aminoglycoside-based antibiotics
- Subject who is receiving a MAO inhibitor(MAOI) or has received MAOI within 14 days of the first investigational drug administration
- Subject taking serotonin reuptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptan), meperidine, or buspirone
- Subject with severely decreased immunity (Severe neutropenia (ANC <0.5×10^9/L) etc.)
- Subject who is expected to die within 2 days due to serious complications of MRSA bacteremia based on the judgment of the investigator
- Body Mass Index (BMI) ≥35 kg/m2
- Subject who is unable to administer drugs orally
- Pregnant or lactating female, female or male with childbearing potential who disagrees with the use of appropriate contraceptive methods during the study and up to 14 days after the last dose of the investigator product
- Subject who has received other clinical trial drugs within 30 days of screening
- Subject who is not suitable for participation in this clinical trial according to the medical findings of investigators
Sites / Locations
- Korea University Ansan Hospital
- Chonnam National University HospitalRecruiting
- Chosun University Hospital
- Asan Medical CenterRecruiting
- Seoul National University Bundang HospitalRecruiting
- Severance Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Combination therapy - Vancomycin IV plus Delpazolid 800 mg, PO, BID
Monotherapy - Vancomycin IV plus Placebo of Delpazolid
Arm Description
Intravenous vancomycin dosed as per 2020 IDSA guideline Doses of 15 to 20 mg/kg (based on actual body weight) administered every 8 to 12 hours as an intermittent infusion are recommended for most patients with normal renal function when assuming a MICBMD of 1 mg/L. Depending on the investigator's judgment, it is allowed to change to daptomycin after at least one week of administration of vancomycin, and also it is allowed to change to oral antibiotics other than oxazolidinones after two weeks of administration of vancomycin (including daptomycin).
Intravenous vancomycin dosed as per 2020 IDSA guideline Doses of 15 to 20 mg/kg (based on actual body weight) administered every 8 to 12 hours as an intermittent infusion are recommended for most patients with normal renal function when assuming a MICBMD of 1 mg/L. Depending on the investigator's judgment, it is allowed to change to daptomycin after at least one week of administration of vancomycin, and also it is allowed to change to oral antibiotics other than oxazolidinones after two weeks of administration of vancomycin (including daptomycin).
Outcomes
Primary Outcome Measures
Overall cure rate by Day 14 (composite response rate: clinical improvement plus clearance of bacteremia)
'Overall cure' means that there are no symptoms of infection that existed when enrolled in the clinical trial, there are no new metastatic infection due to MRSA and no new infection (clinical improvement), and MRSA negative is confirmed twice in a row as a result of blood culture tests ( clearance of bacteremia).
a. If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as 'clearance of bacteremia'.
Secondary Outcome Measures
Overall cure rate by End of Treatment (EOT)
composite response rate: clinical improvement plus clearance of bacteremia
Mortality due to MRSA bacteremia
Proportion of subjects who died due to MRSA bacteremia
Microbiological relapse rate
Defined as a positive blood culture to MRSA when previous ones were negative
Clearance of MRSA bacteremia rate
Proportion of subjects who confirmed MRSA negative two consecutive set in the blood culture test
Persistent MRSA bacteremia rate
Proportion of subjects who have positive results on blood culture tests
Time to clearance of MRSA bacteremia
If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as clearance of bacteremia. The period until the clearance of bacteremia is defined as the period (day) from the date of the first blood culture test within 72 hours prior to randomization with MRSA positive (index blood culture) to the date of the blood culture test with the first negative result confirmed.
Full Information
NCT ID
NCT05225558
First Posted
January 26, 2022
Last Updated
April 16, 2023
Sponsor
LegoChem Biosciences, Inc
1. Study Identification
Unique Protocol Identification Number
NCT05225558
Brief Title
A Phase 2a Study, Effect of Vancomycin With vs Without Delpazolid (LCB01-0371) in Patients With MRSA Bacteremia
Official Title
A Multicenter, Double-blinded, Randomized, Parallel Design, Phase IIa Clinical Trial to Evaluate the Efficacy, Safety and PK of LCB01-0371 With Vancomycin Versus Vancomycin Monotherapy in Patients With MRSA Bacteremia
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 26, 2022 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
November 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
LegoChem Biosciences, Inc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The objectives of this study is to exploratory whether vancomycin + delpazolid is more effective to the standard of treatment (vancomycin)/ for hospitalised adults with MRSA bacteraemia.
Detailed Description
The mortality from S aureus bacteremia is higher for MRSA than for methicillin-susceptible S aureus (MSSA), typically at 20% to 25%.
The current standard therapy for MRSA bacteremia is vancomycin. Vancomycin has many shortcomings, including poor tissue penetration and slow killing time. Vancomycin has reduced efficacy against MRSA and tended to increase the MIC level (called MIC creep). Addition of Delpazolid to Vancomycin could improve the known drawbacks of Vancomycin alone.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MRSA Bacteremia
Keywords
MRSA, Staphylococcus aureus bacteremia, SAB, bloodstream infection, BSI, Bacteremia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Placebo-controlled
Masking
ParticipantInvestigator
Masking Description
Double-blind with placebo
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Combination therapy - Vancomycin IV plus Delpazolid 800 mg, PO, BID
Arm Type
Experimental
Arm Description
Intravenous vancomycin dosed as per 2020 IDSA guideline
Doses of 15 to 20 mg/kg (based on actual body weight) administered every 8 to 12 hours as an intermittent infusion are recommended for most patients with normal renal function when assuming a MICBMD of 1 mg/L.
Depending on the investigator's judgment, it is allowed to change to daptomycin after at least one week of administration of vancomycin, and also it is allowed to change to oral antibiotics other than oxazolidinones after two weeks of administration of vancomycin (including daptomycin).
Arm Title
Monotherapy - Vancomycin IV plus Placebo of Delpazolid
Arm Type
Placebo Comparator
Arm Description
Intravenous vancomycin dosed as per 2020 IDSA guideline
Doses of 15 to 20 mg/kg (based on actual body weight) administered every 8 to 12 hours as an intermittent infusion are recommended for most patients with normal renal function when assuming a MICBMD of 1 mg/L.
Depending on the investigator's judgment, it is allowed to change to daptomycin after at least one week of administration of vancomycin, and also it is allowed to change to oral antibiotics other than oxazolidinones after two weeks of administration of vancomycin (including daptomycin).
Intervention Type
Drug
Intervention Name(s)
Delpazolid
Other Intervention Name(s)
LCB01-0371
Intervention Description
BID, PO
Intervention Type
Drug
Intervention Name(s)
Vancomycin
Intervention Description
IV infusion per 2020 IDSA guideline
Intervention Type
Drug
Intervention Name(s)
Placebo of Delpazolid
Other Intervention Name(s)
Placebo of LCB01-0371
Intervention Description
BID, PO
Primary Outcome Measure Information:
Title
Overall cure rate by Day 14 (composite response rate: clinical improvement plus clearance of bacteremia)
Description
'Overall cure' means that there are no symptoms of infection that existed when enrolled in the clinical trial, there are no new metastatic infection due to MRSA and no new infection (clinical improvement), and MRSA negative is confirmed twice in a row as a result of blood culture tests ( clearance of bacteremia).
a. If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as 'clearance of bacteremia'.
Time Frame
by Day 14
Secondary Outcome Measure Information:
Title
Overall cure rate by End of Treatment (EOT)
Description
composite response rate: clinical improvement plus clearance of bacteremia
Time Frame
by EOT visit (up to 6 weeks)
Title
Mortality due to MRSA bacteremia
Description
Proportion of subjects who died due to MRSA bacteremia
Time Frame
by Test of Cure (TOC) (=4 weeks after EOT (up to 6 weeks))
Title
Microbiological relapse rate
Description
Defined as a positive blood culture to MRSA when previous ones were negative
Time Frame
by TOC (=4 weeks after EOT)
Title
Clearance of MRSA bacteremia rate
Description
Proportion of subjects who confirmed MRSA negative two consecutive set in the blood culture test
Time Frame
Day 3, Day 5, Day 7, Day 14, EOT (up to 6 weeks)
Title
Persistent MRSA bacteremia rate
Description
Proportion of subjects who have positive results on blood culture tests
Time Frame
Day 3, Day 5, Day 7, Day 14
Title
Time to clearance of MRSA bacteremia
Description
If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as clearance of bacteremia. The period until the clearance of bacteremia is defined as the period (day) from the date of the first blood culture test within 72 hours prior to randomization with MRSA positive (index blood culture) to the date of the blood culture test with the first negative result confirmed.
Time Frame
by EOT (up to 6 weeks)
Other Pre-specified Outcome Measures:
Title
Vancomycin minimum inhibitory concentration (MIC) levels
Description
Vancomycin MIC level
Time Frame
up to 6 weeks
Title
Delpazolid MIC levels
Description
Delpazolid MIC level by BMD
Time Frame
up to 6 weeks
Title
Pharmacokinetics (PK) parameters: Cmax
Description
Peak Plasma Concentration (Cmax)
Time Frame
up to 6 weeks
Title
Pharmacokinetics (PK) parameters: AUC(0-last)
Description
the area under the concentration-time curve from dosing (time 0) to the time of the last measured concentration
Time Frame
up to 6 weeks
Title
Pharmacokinetics (PK) parameters: Half-life
Description
Half-life
Time Frame
up to 6 weeks
Title
Pharmacokinetics (PK) parameters: Tmax
Description
time to reach Cmax
Time Frame
up to 6 weeks
Title
Pharmacokinetics (PK) parameters: Cl
Description
Clearance
Time Frame
up to 6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female ≥19 years of age on the date of written consent
Subject who has confirmed positive MRSA at least one set of blood cultures within 72 hours prior to randomization OR, Subject who has confirmed positive MRSA at least one set of blood culture whthin 96 hours prior to randomization and treated with vancomycin at least 72 hours prior to randomization
Subject who has clinical symptoms or signs of MRSA bacteremia according to the judgment of the investigator
Subject who voluntarily decides to participate in this clinical trial after being explained fully, and agrees in writing to implement the clinical trial compliance matters
Exclusion Criteria:
Subject with polymicrobial bacteremia or infections including Gram-negative strain
Subject undergoing or in need of treatment with antiviral or antifungal drugs
Subject who has received treatment for MRSA bacteremia within 3 months of screening (Subjects who have "re-infection" by investigator's judgement may participant in the study.)
Subject who has been administered effective antibiotics against MRSA (Vancomycin, etc.) for more than 96 hours prior to the first investigational product administration. (However, antibiotics effective for MRSA such as vancomycin are allowed to be administered for less than 72 hours.)
Septic shock patients
Subject who has hypersensitivity to vancomycin or linezolid
Subject who has a history of hypersensitivity to peptide-based antibiotics and aminoglycoside-based antibiotics
Subject who is receiving a MAO inhibitor(MAOI) or has received MAOI within 14 days of the first investigational drug administration
Subject taking serotonin reuptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptan), meperidine, or buspirone
Subject with severely decreased immunity (Severe neutropenia (ANC <0.5×10^9/L) etc.)
Subject who is expected to die within 2 days due to serious complications of MRSA bacteremia based on the judgment of the investigator
Body Mass Index (BMI) ≥35 kg/m2
Subject who is unable to administer drugs orally
Pregnant or lactating female, female or male with childbearing potential who disagrees with the use of appropriate contraceptive methods during the study and up to 14 days after the last dose of the investigator product
Subject who has received other clinical trial drugs within 30 days of screening
Subject who is not suitable for participation in this clinical trial according to the medical findings of investigators
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
YunHee Lee
Phone
+82 2 461 0716
Email
yhlee@legochembio.com
Facility Information:
Facility Name
Korea University Ansan Hospital
City
Ansan
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yunhee Lee
Facility Name
Chonnam National University Hospital
City
Gwangju
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yunhee Lee
Facility Name
Chosun University Hospital
City
Gwangju
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yunhee Lee
Facility Name
Asan Medical Center
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yunhee Lee
Facility Name
Seoul National University Bundang Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yunhee Lee
Facility Name
Severance Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yunhee Lee
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Deidentified individual patient data, that underlie the results in published article(s) based on data from the trial which including text, tables, figures will be presented to various stakeholders. This reported will be presented to various stakeholder during various forums or meetings. First results will be disclosed to participants, staff and our site Community Advisory Board. Thereafter we would invite several stakeholders from the community or visit their establishments to review study results. Simultaneously, the studying findings report will be sent to the various regulatory authorities, including the National Department of Health (NDoH). With NDoH and its divisions we will establish needs for further engagement and suggestions for policy or programmatic changes.
IPD Sharing Time Frame
IPD will be provided 1-2 years after and up to 5 years after the publication of the article on the results of the trial.
IPD Sharing Access Criteria
IPD access will be provided for analyses of the related to the aims of research described in the protocol and for individual patient data meta analyses to researches who provide a methodologically sound proposal to lcb_pv@legochembio.com
Learn more about this trial
A Phase 2a Study, Effect of Vancomycin With vs Without Delpazolid (LCB01-0371) in Patients With MRSA Bacteremia
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