Study to Assess Safety, Tolerability and Efficacy of Afabicin in The Treatment of Participants With Bone or Joint Infection Due to Staphylococcus

Study Overview
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Brief Summary
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This is a randomized, active-controlled, open-label study to assess the safety, tolerability and efficacy of Afabicin in the treatment of participants with bone or joint infection due to Staphylococcus aureus [both methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA)] and/or coagulase-negative staphylococci (CoNS) and to compare it to standard of care (SOC).

Official Title
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Randomized Open-label Active-controlled Study to Assess the Safety, Tolerability, and Efficacy of Afabicin IV/Oral in the Treatment of Patients With Bone or Joint Infection Due to Staphylococcus

Conditions
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Bone or Joint Infection

Intervention / Treatment
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* Drug: Afabicin
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Able to provide written informed consent and to comply with study procedures. Diagnosis of bone or joint infection which fulfils the following conditions: a) Infection is due to S. aureus (MSSA or MRSA) and/or CoNS only; and, b) Participants had received no more than 7 days of empiric antibiotics prior to initiating treatment with study drug unless the pathogen isolated was resistant to the administered empiric antibiotics; and, c) Biofilm is not considered to be yet established and/or has been mechanically eradicated; and, d) Infection is not associated with a diabetic foot; and, e) Infection can involve periosteal or soft tissue. Key Exclusion Criteria: Presence of co-infection with non-staphylococcal bacteria at the affected joint or bone site, or in the blood. Participants at an increased risk of developing liver injury. Participants who have medical conditions that increase the risk of QT prolongation. Medical history within the previous 3 months of: myocardial infarction, unstable angina pectoris, coronary artery or cerebral revascularization procedure or stroke, ventricular tachycardia, multifocal ventricular ectopics requiring treatment, or any other clinically relevant symptomatic ventricular arrhythmias. Documented history of alcohol or drug abuse within the previous 12 months. Life expectancy of less than 1 year.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Afabicin<br>In Part A, afabicin will be given intravenous (IV) at a dose 160 milligrams (mg) twice daily (BID) for a minimum of 1 day (2 doses) and up to a maximum of 14 days (2 weeks), followed by a switch to oral Afabicin at a dose of 240 mg BID for the remaining treatment duration. In Part B, participants will be administered with open label afabicin IV at a dose of 55 mg BID for a minimum of 1 day (2 doses) and up to a maximum of 14 days (2 weeks) followed by a switch to oral afabicin at a dose of 80 mg BID for the remaining treatment duration. In certain study conditions a higher dosing regimen of afabicin might be used: afabicin intravenous (IV) at a dose of 80 mg BID for a minimum of 1 day (2 doses) and up to a maximum of 14 days (2 weeks) followed by a switch to oral afabicin at a dose of 120 mg BID for the remaining treatment duration. | Drug: Afabicin<br>* Administered intravenously and orally.<br>|
| Active Comparator: Standard of Care (SOC) (Parts A and B)<br>Participants will be administered with SOC in accordance with local practice and applicable treatment guidelines without exceeding the maximum dosing schedule. | Drug: Standard of Care<br>* Administered with SOC in accordance with local practice and applicable treatment guidelines.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Based on Nature, Incidence, Severity, Seriousness, and Outcome |  | Baseline up to 12-weeks post- end of treatment (EOT) | 
| Change from Baseline in Number of Participants With Incidence of Laboratory Abnormalities |  | Baseline up to Week 12 post- EOT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Clinical Response |  | Days 8, 28, 42, EOT, 4-weeks and 12-weeks post- EOT, as applicable up to Day 168 |