A Phase 2a Study, Effect of Vancomycin With vs Without Delpazolid (LCB01-0371) in Patients With MRSA Bacteremia

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

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.

Study Overview

• Status: Recruiting
• Conditions: MRSA Bacteremia
• Intervention / Treatment: Drug: Delpazolid; Drug: Vancomycin; Drug: Placebo of Delpazolid

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: YunHee Lee; Phone Number: +82 2 461 0716; Email: yhlee@legochembio.com

Study Locations

• Korea, Republic of
  • Ansan, Korea, Republic of
    • Not yet recruiting
    • Korea University Ansan Hospital
    • Contact: Yunhee Lee
  • Gwangju, Korea, Republic of
    • Recruiting
    • Chonnam National University Hospital
    • Contact: Yunhee Lee
  • Gwangju, Korea, Republic of
    • Not yet recruiting
    • Chosun University Hospital
    • Contact: Yunhee Lee
  • Seoul, Korea, Republic of
    • Recruiting
    • Asan Medical Center
    • Contact: Yunhee Lee
  • Seoul, Korea, Republic of
    • Not yet recruiting
    • Severance Hospital
    • Contact: Yunhee Lee
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Bundang Hospital
    • Contact: Yunhee Lee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination therapy - Vancomycin IV plus Delpazolid 800 mg, PO, BID; 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).	Drug: Delpazolid; BID, PO; Other Names: LCB01-0371; Drug: Vancomycin; IV infusion per 2020 IDSA guideline
Placebo Comparator: Monotherapy - Vancomycin IV plus Placebo of Delpazolid; 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).	Drug: Vancomycin; IV infusion per 2020 IDSA guideline; Drug: Placebo of Delpazolid; BID, PO; Other Names: Placebo of LCB01-0371

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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'.	by Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall cure rate by End of Treatment (EOT)	composite response rate: clinical improvement plus clearance of bacteremia	by EOT visit (up to 6 weeks)
Mortality due to MRSA bacteremia	Proportion of subjects who died due to MRSA bacteremia	by Test of Cure (TOC) (=4 weeks after EOT (up to 6 weeks))
Microbiological relapse rate	Defined as a positive blood culture to MRSA when previous ones were negative	by TOC (=4 weeks after EOT)
Clearance of MRSA bacteremia rate	Proportion of subjects who confirmed MRSA negative two consecutive set in the blood culture test	Day 3, Day 5, Day 7, Day 14, EOT (up to 6 weeks)
Persistent MRSA bacteremia rate	Proportion of subjects who have positive results on blood culture tests	Day 3, Day 5, Day 7, Day 14
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.	by EOT (up to 6 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vancomycin minimum inhibitory concentration (MIC) levels	Vancomycin MIC level	up to 6 weeks
Delpazolid MIC levels	Delpazolid MIC level by BMD	up to 6 weeks
Pharmacokinetics (PK) parameters: Cmax	Peak Plasma Concentration (Cmax)	up to 6 weeks
Pharmacokinetics (PK) parameters: AUC(0-last)	the area under the concentration-time curve from dosing (time 0) to the time of the last measured concentration	up to 6 weeks
Pharmacokinetics (PK) parameters: Half-life	Half-life	up to 6 weeks
Pharmacokinetics (PK) parameters: Tmax	time to reach Cmax	up to 6 weeks
Pharmacokinetics (PK) parameters: Cl	Clearance	up to 6 weeks

Collaborators and Investigators

• Sponsor: LegoChem Biosciences, Inc

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2022
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: January 26, 2022
• First Submitted That Met QC Criteria: January 26, 2022
• First Posted (Actual): February 4, 2022

Study Record Updates

• Last Update Posted (Actual): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: MRSA; Bacteremia; BSI; bloodstream infection; SAB; Staphylococcus aureus bacteremia
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Sepsis; Bacteremia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Vancomycin; Delpazolid; Oxazolidinones
• Other Study ID Numbers: LCB35-0371-21-2-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No