Bone or Joint Infection
Conditions
Brief summary
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).
Interventions
DRUGAfabicin
Administered intravenously and orally.
DRUGCefazolin
Administered intravenously.
DRUGVancomycin
Administered intravenously.
DRUGLinezolid
Administered intravenously and orally.
DRUGClindamycin
Administered intravenously and orally.
Sponsors
Debiopharm International SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Up to Day 142 | 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. |
| 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 | Up to Day 142 | 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. |
| Number of Participants With Grade Shift From Baseline in Clinical Chemistry Parameters Based on NCI-CTCAE v4.03 | Up to Day 142 | 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. |
| Number of Participants With Grade Shift From Baseline in Electrolyte Parameters Based on NCI-CTCAE v4.03 | Up to Day 142 | 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. |
| Number of Participants With Grade Shift From Baseline in Coagulation Parameters Based on NCI-CTCAE v4.03 | Up to Day 142 | 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. |
| Number of Participants With Post-baseline Clinically Significant Urinalysis Abnormalities | Up to Day 142 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Response | 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) | 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. |
Countries
Georgia, South Africa, Ukraine
Participant flow
Recruitment details
Participants took part in the study at various investigative sites from 20 February 2019 to 23 April 2025.
Pre-assignment details
A total of 67 participants with bone or joint infection due to Staphylococcus were randomized across Part A and Part B of the study to receive either afabicin or standard of care (SoC).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 55.0 years STANDARD_DEVIATION 5.57 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 60 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 5 | 0 / 3 | 0 / 1 | 0 / 18 | 1 / 22 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 3 / 8 | 3 / 5 | 0 / 3 | 0 / 1 | 10 / 18 | 18 / 22 | 2 / 4 | 3 / 4 |
| serious Total, serious adverse events | 0 / 8 | 1 / 5 | 0 / 3 | 0 / 1 | 3 / 18 | 4 / 22 | 1 / 4 | 0 / 4 |
Outcome results
None listed