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

Sponsor

LegoChem Biosciences, Inc (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05225558

Collaborator

(none)

100

Enrollment

Locations

Arms

18.2

Anticipated Duration (Months)

33.3

Patients Per Site

1.8

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
MRSA Bacteremia	Drug: Delpazolid Drug: Vancomycin Drug: Placebo of Delpazolid	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Placebo-controlledPlacebo-controlled

Masking:

Double (Participant, Investigator)

Masking Description:

Double-blind with placebo

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 26, 2022

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

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.	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.	Drug: Vancomycin IV infusion per 2020 IDSA guideline Drug: Placebo of Delpazolid BID, PO Other Names: Placebo of LCB01-0371

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.

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

Drug: Vancomycin

IV infusion per 2020 IDSA guideline

Drug: Placebo of Delpazolid

BID, PO

Other Names:

Placebo of LCB01-0371

Outcome Measures

Primary Outcome Measures

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

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 culture within 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 72 hours prior to the first administration of the investigational product
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

Contacts and Locations

Locations

	Site	City	Country
1	Chonnam National University Hospital	Gwangju	Korea, Republic of
2	Asan Medical Center	Seoul	Korea, Republic of
3	Seoul National University Bundang Hospital	Seoul	Korea, Republic of