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

MRSA Bacteremia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05225558
• Other study ID #: LCB35-0371-21-2-01
• Status: Terminated
• Phase: Phase 2
• Start date: April 26, 2022
• Est. completion date: February 16, 2024

Study information

• Verified date: January 2024
• Source: LigaChem Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. completion date: February 16, 2024
• Est. primary completion date: February 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bacteremia
• MRSA Bacteremia

Intervention

Drug:
• Delpazolid
BID, PO
• Vancomycin
IV infusion per 2020 IDSA guideline
• Placebo of Delpazolid
BID, PO

Locations

Country	Name	City	State
Korea, Republic of	Korea University Ansan Hospital	Ansan
Korea, Republic of	Chosun University Hospital	Gwangju
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Bundang Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
LigaChem Biosciences, Inc.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Vancomycin minimum inhibitory concentration (MIC) levels	Vancomycin MIC level	up to 6 weeks
Other	Delpazolid MIC levels	Delpazolid MIC level by BMD	up to 6 weeks
Other	Pharmacokinetics (PK) parameters: Cmax	Peak Plasma Concentration (Cmax)	up to 6 weeks
Other	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
Other	Pharmacokinetics (PK) parameters: Half-life	Half-life	up to 6 weeks
Other	Pharmacokinetics (PK) parameters: Tmax	time to reach Cmax	up to 6 weeks
Other	Pharmacokinetics (PK) parameters: Cl	Clearance	up to 6 weeks
Primary	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	Overall cure rate by End of Treatment (EOT)	composite response rate: clinical improvement plus clearance of bacteremia	by EOT visit (up to 6 weeks)
Secondary	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))
Secondary	Microbiological relapse rate	Defined as a positive blood culture to MRSA when previous ones were negative	by TOC (=4 weeks after EOT)
Secondary	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)
Secondary	Persistent MRSA bacteremia rate	Proportion of subjects who have positive results on blood culture tests	Day 3, Day 5, Day 7, Day 14
Secondary	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)