LYS228 PK, Clinical Response, Safety and Tolerability in Patients With Complicated Intra-abdominal Infection (cIAI)

Study Overview
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Brief Summary
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The purpose of the study was to evaluate whether LYS228 can be developed for the treatment of complicated intra-abdominal infections. It was planned that LYS228 exposure across patients with varying renal function would be evaluated during the study to confirm that LYS228 concentrations are predicted to be adequate to treat the patient population. It was planned that the PK exposure of the initial 8 patients would be analyzed. PK analysis was not conducted as per protocol the first analysis required 8 patients.

Official Title
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A Randomized, Controlled, Evaluator-blinded, Multi-center Study to Evaluate LYS228 Pharmacokinetics, Clinical Response, Safety, and Tolerability in Patients With Complicated Intra-abdominal Infection

Conditions
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Intra-abdominal Infections

Intervention / Treatment
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* Drug: LYS228
* Drug: Standard of care therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients 18 to 85 years of age with visual confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis including at least one inclusionary diagnosis during surgical intervention. Exclusion Criteria Any of the excluded diagnoses: abdominal wall abscess, small bowel obstruction, traumatic bowel perforation undergoing surgery within 12 hours, perforation of gastroduodenal ulcer with surgery within 24 hours, an intra-abdominal process that is not likely caused by infection. Pre-operative treatment of any duration with non-study Drug systemic antibiotic therapy for peritonitis or abscess is not allowed unless certain criteria are met. Concomitant bacterial infection at time of enrollment requiring non-Study Drug antibiotics and that may interfere with the evaluation of clinical response to the study antibiotic. Known non-abdominal source of infection, including endocarditis, osteomyelitis, abscess, meningitis, or pneumonia diagnosed within 7 days prior to enrollment. Patient has an Acute Physiology and Chronic Health Evaluation II (APACHE II) score > 30 or is considered, in the judgement of the investigator, unlikely to survive 4 weeks (e.g. rapidly progressive terminal illness, including septic shock). Patients that meet sepsis criteria as defined by the quick sequential sepsis-related organ failure assessment (qSOFA). Women of child-bearing potential unless they are using highly effective methods of contraception during dosing and for 7 days after stopping study treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LYS228<br>IV infusion every 6 hours for at least 5 days | Drug: LYS228<br>* LYS228 IV infusion every 6 hours<br>|
| Active Comparator: Standard of care<br>IV infusion of standard of care antibiotics for at least 5 days | Drug: Standard of care therapy<br>* IV infusion of standard of care antibiotics<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Success at Day 28 | Clinical success is defined as resolution, or substantial improvement (i.e. reduction of severity of all baseline signs and symptoms and worsening of none) of all or most baseline signs and symptoms of cIAI infection without the need for additional antibiotic therapy other than any oral antibiotics given to complete treatment at home following discontinuation of Study Drug and no drainage or surgical reintervention required 96 hours after the start of Study Drug. | Day 28 | 
| Plasma Pharmacokinetics (PK) of LYS228: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) | Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5 | Day 5 | 
| Plasma Pharmacokinetics (PK) of LYS228: The Observed Maximum Plasma Concentration Following Drug Administration (Cmax) | Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5 | Day 5 | 
| Plasma Pharmacokinetics (PK) of LYS228: The Time to Reach the Maximum Concentration After Drug Administration (Tmax) | Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5 | Day 5 | 
| Plasma Pharmacokinetics (PK) of LYS228: The Systemic (or Total Body) Clearance From Plasma Following Intravenous Administration (CL) | Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5 | Day 5 | 
| Plasma Pharmacokinetics (PK) of LYS228: The Volume of Distribution at Steady State Following Intravenous Administration (Vss) | Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5 | Day 5 | 
| Plasma Pharmacokinetics (PK) of LYS228: The Terminal Elimination Half-life (T1/2) | Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5 | Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Adverse Events | Number of patients with at least one Adverse Event | Daily | 
| Microbiological Response at Day 28 | Microbiologic success at 28 days after randomization determined by microbial growth in culture from the intra-abdominal focus of infection when available or presumed eradication based on clinical success | Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LYS228, Intra-abdominal infection, beta-lactam antibiotics, creatinine clearance, enterobacteriaceae