Oral Sodium Fusidate (CEM-102) for the Treatment of Staphylococcal Bone or Joint Infections

Study Overview
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Brief Summary
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To evaluate the safety and effectiveness of oral sodium fusidate (CEM-102) as chronic antibiotic for the treatment of bone or joint infections.

Detailed Description
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Prospective, open-label, non-randomized, single-arm trial to evaluate the safety and effectiveness of CEM-102 for chronic antibiotic suppressive therapy of bone or joint infections. Subjects enrolling in this study must have a refractory staphylococcal bone or joint infection that requires suppressive antibiotic therapy (e.g. having an infection that cannot be managed by complete removal of the infected bone or foreign material, a refractory infection not responding to previous treatment, or not being a candidate for long-term intravenous antibiotic therapy).

Official Title
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An Open-Label, Non-Randomized, Single-Arm, Multi-Center Study to Evaluate Oral Sodium Fusidate (CEM-102) for the Treatment of Staphylococcal Bone or Joint Infections in Subjects for Whom Chronic Antibiotic Suppressive Therapy is Indicated

Conditions
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Refractory Bone or Joint Infections

Intervention / Treatment
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* Drug: sodium fusidate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adolescents between 12 and 18 years must weigh >60 kg Bone or joint infection due to an inclusionary pathogen demonstrated from a culture from samples obtained within 6 weeks prior to enrollment Not a candidate, as determined by the Investigator, for suitable alternative therapy After completion of 1-2 weeks of the companion antibiotic, must be a suitable candidate for CEM-102 monotherapy for chronic treatment Exclusion Criteria: Requires concomitant treatment with OATP1B1 and OATP1B3 substrates, in particular, statins (HMG-CoA reductase inhibitors) Known severe renal impairment, as indicated by estimated CrCl <30 mL/min (by Cockcroft-Gault calculation) Evidence of significant liver disease: ALT >3 × ULN or direct bilirubin >ULN; known cirrhosis with decompensation (i.e. Child-Pugh Class B or C disease)

Ages Eligible for Study
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Minimum Age: 12 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CEM-102 (Sodium fusidate)<br>1500 mg by mouth every 12 hours for 2 doses, then 600 mg by mouth every 12 hours thereafter, until end of therapy: 6 months of treatment; or 24 months of treatment (if continued on chronic suppressive therapy) | Drug: sodium fusidate<br> <br> * Other names: fusidic acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Success at 6 Months | Number of participants in the intent to treat (ITT) analysis set who meet all the criteria for clinical success at the 6-Month Visit. Clinical success was defined to occur when subjects met all of the following criteria: 1) Subject was not hospitalized due to worsening of the study-qualifying orthopedic infection. 2) Subject did not undergo a definitive surgical procedure (such as amputation). 2) No additional antibiotics (after completion of companion antibiotics) are required for treatment of the orthopedic infection due to the inclusionary pathogen. 3) Wound is closed, or the open area decreased in size (L x W) and, if a skin graft was done, the graft remains viable without evidence of infection. 4) No purulent discharge from the surgical wound, or new or recurring sinus tract. 5) No worsening of redness, tenderness, or swelling at the primary infection site. 5) No bacteremia | 6 months after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | Number of participants with TEAEs, SAEs, deaths, and discontinuations due to AEs. Treatment-emergent adverse events, defined as events with a start date on or after the initiation of study drug through 28 days after the last dose of study drug, are reported. | Entire study period - up to 24 months | 
| Clinical Success at 9 Months | Number of participants in the ITT analysis set who meet all the criteria for clinical success at the 9-Month Visit. Clinical success was defined to occur when subjects met all of the following criteria: 1) Subject was not hospitalized due to worsening of the study-qualifying orthopedic infection. 2) Subject did not undergo a definitive surgical procedure (such as amputation). 2) No additional antibiotics (after completion of companion antibiotics) are required for treatment of the orthopedic infection due to the inclusionary pathogen. 3) Wound is closed, or the open area decreased in size (L x W) and, if a skin graft was done, the graft remains viable without evidence of infection. 4) No purulent discharge from the surgical wound, or new or recurring sinus tract. 5) No worsening of redness, tenderness, or swelling at the primary infection site. 5) No bacteremia | 9 months after start of treatment | 
| Clinical Success at 12 Months | Number of participants in the ITT analysis set who meet all the criteria for clinical success at the 12-Month Visit. Clinical success was defined to occur when subjects met all of the following criteria: 1) Subject was not hospitalized due to worsening of the study-qualifying orthopedic infection. 2) Subject did not undergo a definitive surgical procedure (such as amputation). 2) No additional antibiotics (after completion of companion antibiotics) are required for treatment of the orthopedic infection due to the inclusionary pathogen. 3) Wound is closed, or the open area decreased in size (L x W) and, if a skin graft was done, the graft remains viable without evidence of infection. 4) No purulent discharge from the surgical wound, or new or recurring sinus tract. 5) No worsening of redness, tenderness, or swelling at the primary infection site. 5) No bacteremia | 12 months after start of treatment | 
| Clinical Success at 15 Months | Number of participants in the ITT analysis set who meet all the criteria for clinical success at the 15-Month Visit. Clinical success was defined to occur when subjects met all of the following criteria: 1) Subject was not hospitalized due to worsening of the study-qualifying orthopedic infection. 2) Subject did not undergo a definitive surgical procedure (such as amputation). 2) No additional antibiotics (after completion of companion antibiotics) are required for treatment of the orthopedic infection due to the inclusionary pathogen. 3) Wound is closed, or the open area decreased in size (L x W) and, if a skin graft was done, the graft remains viable without evidence of infection. 4) No purulent discharge from the surgical wound, or new or recurring sinus tract. 5) No worsening of redness, tenderness, or swelling at the primary infection site. 5) No bacteremia | 15 months after start of treatment | 
| Clinical Success at 18 Months | Number of participants in the ITT analysis set who meet all the criteria for clinical success at the 18-Month Visit. Clinical success was defined to occur when subjects met all of the following criteria: 1) Subject was not hospitalized due to worsening of the study-qualifying orthopedic infection. 2) Subject did not undergo a definitive surgical procedure (such as amputation). 2) No additional antibiotics (after completion of companion antibiotics) are required for treatment of the orthopedic infection due to the inclusionary pathogen. 3) Wound is closed, or the open area decreased in size (L x W) and, if a skin graft was done, the graft remains viable without evidence of infection. 4) No purulent discharge from the surgical wound, or new or recurring sinus tract. 5) No worsening of redness, tenderness, or swelling at the primary infection site. 5) No bacteremia | 18 months after start of treatment | 
| Clinical Success at 21 Months | Number of participants in the ITT analysis set who meet all the criteria for clinical success at the 21-Month Visit. Clinical success was defined to occur when subjects met all of the following criteria: 1) Subject was not hospitalized due to worsening of the study-qualifying orthopedic infection. 2) Subject did not undergo a definitive surgical procedure (such as amputation). 2) No additional antibiotics (after completion of companion antibiotics) are required for treatment of the orthopedic infection due to the inclusionary pathogen. 3) Wound is closed, or the open area decreased in size (L x W) and, if a skin graft was done, the graft remains viable without evidence of infection. 4) No purulent discharge from the surgical wound, or new or recurring sinus tract. 5) No worsening of redness, tenderness, or swelling at the primary infection site. 5) No bacteremia | 21 months after start of treatment | 
| Clinical Success at 24 Months | Number of participants in the ITT analysis set who meet all the criteria for clinical success at the 24-Month Visit. Clinical success was defined to occur when subjects met all of the following criteria: 1) Subject was not hospitalized due to worsening of the study-qualifying orthopedic infection. 2) Subject did not undergo a definitive surgical procedure (such as amputation). 2) No additional antibiotics (after completion of companion antibiotics) are required for treatment of the orthopedic infection due to the inclusionary pathogen. 3) Wound is closed, or the open area decreased in size (L x W) and, if a skin graft was done, the graft remains viable without evidence of infection. 4) No purulent discharge from the surgical wound, or new or recurring sinus tract. 5) No worsening of redness, tenderness, or swelling at the primary infection site. 5) No bacteremia | 24 months after start of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fusidic acid, prosthetic joint infections, bone infections, osteomyelitis