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

Phase 2TerminatedNCT05225558

LigaChem Biosciences, Inc.40 enrolled

Overview

The objectives of this study is to exploratory whether Vancomycin + Delpazolid is more effective to the standard of treatment (Vancomycin)/ for hospitalized adults with MRSA bacteraemia.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

MRSA Bacteremia

Interventions

DelpazolidDRUG

BID, PO

VancomycinDRUG

IV infusion per 2020 IDSA guideline

Placebo of DelpazolidDRUG

BID, PO

Eligibility

Sex: ALLMin age: 19 Years

Medical Language ↔ Plain English

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

Locations (6)

Chosun University Hospital

Gwangju, South Korea

Chonnam National University Hospital

Gwangju, South Korea

Seoul National University Bundang Hospital

Gyeonggi-do, South Korea

Korea University Ansan Hospital

Gyeonggi-do, South Korea

Outcomes

Primary Outcomes

Overall Cure Rate at Day 14 After the Start of Treatment (Composite Response Rate: Clinical Improvement Plus Clearance of Bacteremia)_FAS

* '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). 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'. * Composite Response rate = (number of participants showing overall cure at Day 14/number of participants in each treatment group) x 100

Time frame: at Day 14

Overall Cure Rate at Day 14 After the Start of Treatment (Composite Response Rate: Clinical Improvement Plus Clearance of Bacteremia)_PPS

Time frame: at Day 14

Secondary Outcomes

Overall Cure Rate by End of Treatment (EOT)_FAS

Data from ClinicalTrials.gov

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Severance Hospital

Seoul, South Korea

Asan Medical Center

Seoul, South Korea

Time frame: Day 7 visit and EOT (up to 6 weeks) visit

Overall Cure Rate by End of Treatment (EOT)_PPS

Time frame: Day 7 visit and EOT (up to 6 weeks) visit

Mortality From MRSA Bacteremia by EOT_FAS

* Proportion of participants who died due to MRSA bacteremia * Overall mortality = (number of participants who died/number of participants in each treatment group) x 100

Time frame: During the treatment period (from the first administration to EOT (up to 6 weeks))

Mortality From MRSA Bacteremia by EOT_PPS

* Proportion of participants who died due to MRSA bacteremia * Overall mortality = (number of participants who died/number of participants in each treatment group) x 100

Time frame: During the treatment period (from the first administration to EOT (up to 6 weeks))

Relapse Rate of MRSA bacteremia_FAS

* Defined as a positive blood culture to MRSA when previous ones were negative * Relapse rate of MRSA bacteremia = (number of participants with Relapse of MRSA bacteremia after clearance of MRSA bacteremia until TOC visit/number of participants with clearance of MRSA bacteremia in each treatment group) x 100

Time frame: from the first administration to TOC (4 weeks after EOT)

Relapse Rate of MRSA bacteremia_PPS

Time frame: from the first administration to TOC (4 weeks after EOT)

Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_FAS

* Proportion of participants who confirmed MRSA negative two consecutive set in the blood culture test * Clearance Rate = (number of subjects who achieved clearance at each visit/number of subjects in each treatment group) x 100

Time frame: Day 3, Day 5, Day 7, Day 14, EOT (up to 6 weeks)

Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_PPS

Time frame: Day 3, Day 5, Day 7, Day 14, EOT (up to 6 weeks)

Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_FAS

* Proportion of participants who have positive results on blood culture tests * Persistent rate of bacteremia = (number of subjects who showing persistent bacteremia up to each visit /number of subjects in each treatment group up to each visit) x 100

Time frame: Day 3, Day 5, Day 7, Day 14

Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_PPS

Time frame: Day 3, Day 5, Day 7, Day 14

Time to Clearance of MRSA bacteremia_FAS

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)

Time to Clearance of MRSA bacteremia_PPS

Time frame: by EOT (up to 6 weeks)