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

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

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).

Study Overview

• Status: Terminated
• Conditions: Bone or Joint Infection
• Intervention / Treatment: Drug: Afabicin; Drug: Cefazolin; Drug: Vancomycin; Drug: Linezolid; Drug: Clindamycin

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2

Contacts and Locations

Study Locations

• Georgia
  • Akhalts'ikhe, Georgia, 0800
    • Georgian Clinics JSC
  • Kutaisi, Georgia, 4600
    • West Georgia Medical Center LLC
  • Tbilisi, Georgia, 0141
    • LEPL The First University Clinic of Tbilisi State Medical University
  • Tbilisi, Georgia, 0144
    • Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic LLC
  • Tbilisi, Georgia, 0101
    • Malkhaz Katsiashvili Multiprofile Emergency Medicine Center LLC
  • Tbilisi, Georgia, 0160
    • Academician Vakhtang Bochorishvili Clinic LTD
  • Tbilisi, Georgia, 0186
    • Caucasus Medical Center LLC
• South Africa
  • Benoni, South Africa, 1500
    • Worthwhile Clinical Trials, Lakeview Hospital
  • Pretoria, South Africa, 0002
    • Clinical Research Unit, University of Pretoria
  • Pretoria, South Africa, 0157
    • Global Clinical Trials (Pty) Ltd
• Ukraine
  • Dnipro, Ukraine, 49027
    • Dnipropetrovsk Regional Clinical Hospital
  • Ivano-Frankivsk, Ukraine, 76008
    • Regional Clinical Hospital under Ivano-Frankivsk Regional Council
  • Kharkiv, Ukraine, 61176
    • Kharkiv Regional Clinical Traumatology Hospital
  • Kyiv, Ukraine, 04107
    • Kyiv Regional Clinical Hospital
  • Kyiv, Ukraine, 01601
    • Institute of Traumatology and Orthopedics
  • Kyiv, Ukraine
    • Kyiv City Clinical Hospital #8 under the Executive Body of Kyiv City Council (Kyiv City State Administration)
  • Vinnytsia, Ukraine, 21028
    • Vinnytsya Regional Clinical Hospital
  • Vynnyky, Ukraine, 79495
    • Lviv Regional Hospital of Veterans of Wars and Repressed after Yurii Lypa
  • Zaporizhia, Ukraine, 69065
    • City Hospital #9 under Zaporizhia City Council

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Afabicin: Cohort 1; Participants received afabicin intravenously (IV) at a dose of 160 milligrams (mg), twice daily (BID), followed by a switch to oral afabicin at a dose of 240 mg, BID, for 2-3 weeks.	Drug: Afabicin; Administered intravenously and orally.
Experimental: Part A: Afabicin: Cohort 2; Participants received afabicin IV at a dose of 160 mg, BID, followed by a switch to oral afabicin at a dose of 240 mg, BID, for 3-6 weeks.	Drug: Afabicin; Administered intravenously and orally.
Active Comparator: Part A: SoC: Cohort 1; Participants with oxacillin-/methicillin-susceptible staphylococci were administered with either cefazolin or vancomycin or linezolid or clindamycin, IV or linezolid or clindamycin, orally; participants with oxacillin-/methicillin-resistant staphylococci were administered either vancomycin or clindamycin or linezolid, IV or linezolid or clindamycin, orally, as part of SoC in accordance with local practice and applicable treatment guidelines without exceeding the maximum dosing schedule.	Drug: Cefazolin; Administered intravenously.; Drug: Vancomycin; Administered intravenously.; Drug: Linezolid; Administered intravenously and orally.; Drug: Clindamycin; Administered intravenously and orally.
Active Comparator: Part A: SoC: Cohort 2; Participants with oxacillin-/methicillin-susceptible staphylococci were administered with either cefazolin or vancomycin or linezolid or clindamycin, IV or linezolid or clindamycin, orally; participants with oxacillin-/methicillin-resistant staphylococci were administered either vancomycin or clindamycin or linezolid, IV or linezolid or clindamycin, orally, as part of SoC in accordance with local practice and applicable treatment guidelines without exceeding the maximum dosing schedule.	Drug: Cefazolin; Administered intravenously.; Drug: Vancomycin; Administered intravenously.; Drug: Linezolid; Administered intravenously and orally.; Drug: Clindamycin; Administered intravenously and orally.
Experimental: Part B: Afabicin: Cohort 1; Participants received afabicin IV at a dose of 55 mg, BID, followed by a switch to oral afabicin at a dose of 80 mg, BID, for 2-3 weeks.	Drug: Afabicin; Administered intravenously and orally.
Experimental: Part B: Afabicin: Cohort 2; Participants received afabicin IV at a dose of 55 mg, BID, followed by a switch to oral afabicin at a dose of 80 mg, BID, for 3-6 weeks.	Drug: Afabicin; Administered intravenously and orally.
Active Comparator: Part B: SoC: Cohort 1; Participants with oxacillin-/methicillin-susceptible staphylococci were administered with either cefazolin or vancomycin or linezolid or clindamycin, IV or linezolid or clindamycin, orally; participants with oxacillin-/methicillin-resistant staphylococci were administered either vancomycin or clindamycin or linezolid, IV or linezolid or clindamycin, orally, as part of SoC in accordance with local practice and applicable treatment guidelines without exceeding the maximum dosing schedule.	Drug: Cefazolin; Administered intravenously.; Drug: Vancomycin; Administered intravenously.; Drug: Linezolid; Administered intravenously and orally.; Drug: Clindamycin; Administered intravenously and orally.
Active Comparator: Part B: SoC: Cohort 2; Participants with oxacillin-/methicillin-susceptible staphylococci were administered with either cefazolin or vancomycin or linezolid or clindamycin, IV or linezolid or clindamycin, orally; participants with oxacillin-/methicillin-resistant staphylococci were administered either vancomycin or clindamycin or linezolid, IV or linezolid or clindamycin, orally, as part of SoC in accordance with local practice and applicable treatment guidelines without exceeding the maximum dosing schedule.	Drug: Cefazolin; Administered intravenously.; Drug: Vancomycin; Administered intravenously.; Drug: Linezolid; Administered intravenously and orally.; Drug: Clindamycin; Administered intravenously and orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Adverse Event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product. TEAE is any undesirable event either not present prior to medical treatment or worsening (in intensity or frequency) following treatment. SAE is defined as any untoward medical occurrence that at any dose: results in death; is life-threatening (i.e., puts the patient at immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect, or is otherwise medically significant.	Up to Day 142
Number of Participants With Grade Shift From Baseline in Hematology Parameters Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 4.03	Laboratory abnormalities were graded according to NCI CTCAE v4.03. Grade 0 indicates a normal value; Grades 1-4 represent increasing severity of abnormalities outside the normal range. "High" and "Low" indicate values above and below the normal range, respectively. At baseline (last assessment prior to randomization), both "High, Grade 0" and "Low, Grade 0" indicate normal values and identify the direction of the subsequent post-baseline shift. Participants were evaluated separately for High and Low shifts. Participant could contribute to both analyses if shifts occurred in opposite directions at different assessments. These categories are not mutually exclusive; therefore, counts should not be summed across directions, as they may exceed the number of participants analyzed. Participant could not be classified as both High and Low at the same assessment. Only categories with at least one participant showing a shift were reported.	Up to Day 142
Number of Participants With Grade Shift From Baseline in Clinical Chemistry Parameters Based on NCI-CTCAE v4.03	Laboratory abnormalities were graded according to NCI CTCAE v4.03. Grade 0 indicates a normal value; Grades 1-4 represent increasing severity of abnormalities outside the normal range. "High" and "Low" indicate values above and below the normal range, respectively. At baseline (last assessment prior to randomization), both "High, Grade 0" and "Low, Grade 0" indicate normal values and identify the direction of the subsequent post-baseline shift. Participants were evaluated separately for High and Low shifts. Participant could contribute to both analyses if shifts occurred in opposite directions at different assessments. These categories are not mutually exclusive; therefore, counts should not be summed across directions, as they may exceed the number of participants analyzed. Participant could not be classified as both High and Low at the same assessment. Only categories with at least one participant showing a shift were reported.	Up to Day 142
Number of Participants With Grade Shift From Baseline in Electrolyte Parameters Based on NCI-CTCAE v4.03	Laboratory abnormalities were graded according to NCI CTCAE v4.03. Grade 0 indicates a normal value; Grades 1-4 represent increasing severity of abnormalities outside the normal range. "High" and "Low" indicate values above and below the normal range, respectively. At baseline (last assessment prior to randomization), both "High, Grade 0" and "Low, Grade 0" indicate normal values and identify the direction of the subsequent post-baseline shift. Participants were evaluated separately for High and Low shifts. Participant could contribute to both analyses if shifts occurred in opposite directions at different assessments. These categories are not mutually exclusive; therefore, counts should not be summed across directions, as they may exceed the number of participants analyzed. Participant could not be classified as both High and Low at the same assessment. Only categories with at least one participant showing a shift were reported.	Up to Day 142
Number of Participants With Grade Shift From Baseline in Coagulation Parameters Based on NCI-CTCAE v4.03	Laboratory abnormalities were graded according to NCI CTCAE v4.03. Grade 0 indicates a normal value; Grades 1-4 represent increasing severity of abnormalities outside the normal range. "High" and "Low" indicate values above and below the normal range, respectively. At baseline (last assessment prior to randomization), both "High, Grade 0" and "Low, Grade 0" indicate normal values and identify the direction of the subsequent post-baseline shift. Participants were evaluated separately for High and Low shifts. Participant could contribute to both analyses if shifts occurred in opposite directions at different assessments. These categories are not mutually exclusive; therefore, counts should not be summed across directions, as they may exceed the number of participants analyzed. Participant could not be classified as both High and Low at the same assessment. Only categories with at least one participant showing a shift were reported.	Up to Day 142
Number of Participants With Post-baseline Clinically Significant Urinalysis Abnormalities	Clinical significance of abnormalities in urinalysis was determined based on the investigator's discretion. Baseline is defined as the last assessment prior to the randomization.	Up to Day 142

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinical Response	Clinical response was based on the improvement of disease-specific signs and symptoms. Responders are defined as participants meeting all the following criteria: improvement of disease-specific signs and symptoms and no new signs, symptoms or complications attributable to the initial infection; No evidence of drainage, sinus tract formation or infection-related bone instability; No requirement for subsequent antibiotics with activity against Staphylococcus to treat the initial infection after the start of study treatment; Microbiological eradication of the baseline pathogen (if post-baseline sample[s] are available); Imaging test at 12 weeks post-EOT showing no worsening of baseline pathology or presence of signs indicating resolution or healing of the infection. Percentages are rounded off.	Part A: At Day 8, EOT (up to Day 22), 4-weeks post-EOT (up to Day 50), and 12-weeks post-EOT (up to Day 130); Part B: At Day 8, Day 28, Day 42, EOT (up to Day 43), 4-weeks post-EOT (up to Day 73), and 12-weeks post-EOT (up to Day 142)

Collaborators and Investigators

• Sponsor: Debiopharm International SA

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2019
• Primary Completion (Actual): April 23, 2025
• Study Completion (Actual): April 23, 2025

Study Registration Dates

• First Submitted: October 26, 2018
• First Submitted That Met QC Criteria: October 26, 2018
• First Posted (Actual): October 29, 2018

Study Record Updates

• Last Update Posted (Actual): September 9, 2026
• Last Update Submitted That Met QC Criteria: September 7, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Pathologic Processes; Disease Attributes; Arthritis; Joint Diseases; Infections; Communicable Diseases; Arthritis, Infectious; Peptides; Amino Acids, Peptides, and Proteins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Carbohydrates; Acids, Acyclic; Carboxylic Acids; Glycosides; Amides; Glycoconjugates; Pyrrolidines; Lincomycin; Lincosamides; beta-Lactams; Lactams; Cephalosporins; Thiazines; Acetamides; Acetates; Oxazolidinones; Oxazoles; Glycopeptides; Linezolid; Vancomycin; Cefazolin; Clindamycin; afabicin
• Other Study ID Numbers: Debio 1450-BJI-205; 2017-002854-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No