Clinical trial NCT05225558: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: MRSA Bacteremia
Keywords: MRSA
Staphylococcus aureus bacteremia
SAB
bloodstream infection
BSI
Bacteremia
Lead sponsor: LigaChem Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-04
Enrollment: 40
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Placebo-controlled
Primary purpose: TREATMENT

Brief summary: 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.

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.

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

Primary outcomes:
measure: Overall Cure Rate at Day 14 After the Start of Treatment (Composite Response Rate: Clinical Improvement Plus Clearance of Bacteremia)_FAS
timeFrame: at Day 14
measure: Overall Cure Rate at Day 14 After the Start of Treatment (Composite Response Rate: Clinical Improvement Plus Clearance of Bacteremia)_PPS
timeFrame: at Day 14
Secondary outcomes:
measure: Overall Cure Rate by End of Treatment (EOT)_FAS
timeFrame: Day 7 visit and EOT (up to 6 weeks) visit
measure: Overall Cure Rate by End of Treatment (EOT)_PPS
timeFrame: Day 7 visit and EOT (up to 6 weeks) visit
measure: Mortality From MRSA Bacteremia by EOT_FAS
timeFrame: During the treatment period (from the first administration to EOT (up to 6 weeks))
measure: Mortality From MRSA Bacteremia by EOT_PPS
timeFrame: During the treatment period (from the first administration to EOT (up to 6 weeks))
measure: Relapse Rate of MRSA bacteremia_FAS
timeFrame: from the first administration to TOC (4 weeks after EOT)
measure: Relapse Rate of MRSA bacteremia_PPS
timeFrame: from the first administration to TOC (4 weeks after EOT)
measure: Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_FAS
timeFrame: Day 3, Day 5, Day 7, Day 14, EOT (up to 6 weeks)
measure: Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_PPS
timeFrame: Day 3, Day 5, Day 7, Day 14, EOT (up to 6 weeks)
measure: Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_FAS
timeFrame: Day 3, Day 5, Day 7, Day 14
measure: Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_PPS
timeFrame: Day 3, Day 5, Day 7, Day 14
measure: Time to Clearance of MRSA bacteremia_FAS
timeFrame: by EOT (up to 6 weeks)
measure: Time to Clearance of MRSA bacteremia_PPS
timeFrame: by EOT (up to 6 weeks)
Other outcomes:
measure: Vancomycin MIC Level
timeFrame: at Screening visit (baseline)
measure: Delpazolid MIC Levels
timeFrame: Screening (Baseline), Day 14, EOT
measure: Pharmacokinetics (PK) parameters_AUC,ss
timeFrame: Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product.
measure: Pharmacokinetics (PK) parameters_Cmax,ss
timeFrame: Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product.
measure: Pharmacokinetics (PK) parameters_Cmin,ss
timeFrame: Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product.
measure: Pharmacokinetics (PK) parameters_Tmax,ss
timeFrame: Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product.
measure: Pharmacokinetics (PK) parameters_t1/2β
timeFrame: Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product.
measure: Pharmacokinetics (PK) parameters_MRT,ss
timeFrame: Plasma samples for pharmacokinetic evaluation were collected once at each timepoint on Day 1 and between Day 3 and end of treatment (EOT), specifically at 30 minutes to 1 hour and 2 to 8 hours after administration of the investigational product.
Locations:
city: Gwangju
country: Korea, Republic of
facility: Chosun University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Seoul National University Bundang Hospital
name: Hongbin Kim
role: PRINCIPAL_INVESTIGATOR
References: