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

Debiopharm

Status and phase: Enrolling; Phase 2

Conditions: Bone or Joint Infection

Treatments: Drug: Afabicin; Drug: Standard of Care

Study type: Interventional

Funder types: Industry

Identifiers

NCT03723551

Debio 1450-BJI-205

Details and patient eligibility

About

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).

Enrollment: 111 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 an ischiatic or a sacral osteomyelitis; 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.

• For patients with DFO:

  1. Severe peripheral arterial disease (PAD) requiring revascularization; however, patients with peripheral artery disease are eligible for inclusion, provided they have undergone successful revascularization or it has been deemed unnecessary by a vascular surgeon
  2. Necrotizing fasciitis or gangrene requiring complete lower extremity amputation (of all infected bone and soft tissue).
  3. Patients with Charcot foot (suspected neuro-osteoarthropathy according to Investigator's judgment).
  4. Need for digital amputation.

• Life expectancy of less than 1 year.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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111 participants in 2 patient groups

Afabicin

Experimental group

Description:

In Part A, afabicin will be given intravenous (IV) at a dose 160 milligrams (mg) twice daily (BID) for a minimum of 1 day (at least 1 dose) 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 (at least 1 dose) 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 (at least 1 dose) 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.

Treatment:

Drug: Afabicin

Standard of Care (SOC) (Parts A and B)

Active Comparator group

Description:

Participants will be administered with SOC in accordance with local practice and applicable treatment guidelines without exceeding the maximum dosing schedule.

Treatment:

Drug: Standard of Care