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

LigaChem Biosciences

Status and phase: Terminated; Phase 2

Conditions: MRSA Bacteremia

Treatments: Drug: Placebo of Delpazolid; Drug: Vancomycin; Drug: Delpazolid

Study type: Interventional

Funder types: Industry

Identifiers

NCT05225558

LCB35-0371-21-2-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 patients

Sex: All

Ages: 19+ years old

Volunteers: No 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 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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40 participants in 2 patient groups, including a placebo group

Combination therapy - Vancomycin IV plus Delpazolid 800 mg, PO, BID

Experimental group

Description:

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).

Treatment:

Drug: Delpazolid

Drug: Vancomycin

Monotherapy - Vancomycin IV plus Placebo of Delpazolid

Placebo Comparator group

Description:

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).

Treatment:

Drug: Vancomycin

Drug: Placebo of Delpazolid