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

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).

• sodium fusidate (Drug), also known as CEM-102, fusidic acid

Primary outcomes

• Clinical Success at 6 Months [6 months after start of treatment]: 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

Secondary outcomes

• Safety and Tolerability [Entire study period - up to 24 months]: 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.
• Clinical Success at 9 Months [9 months after start of treatment]: 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
• Clinical Success at 12 Months [12 months after start of treatment]: 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
• Clinical Success at 15 Months [15 months after start of treatment]: 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
• Clinical Success at 18 Months [18 months after start of treatment]: 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
• Clinical Success at 21 Months [21 months after start of treatment]: 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
• Clinical Success at 24 Months [24 months after start of treatment]: 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

Sex: All, ages: 12 Years to any

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)

Participant flow

Outcome results

• Clinical Success at 6 Months (Primary), Count of participants, Participants: CEM-102 (Sodium Fusidate) 18
• Safety and Tolerability (Secondary), Count of participants, Participants: CEM-102 (Sodium Fusidate) 29
• Clinical Success at 9 Months (Secondary), Count of participants, Participants: CEM-102 (Sodium Fusidate) 15
• Clinical Success at 12 Months (Secondary), Count of participants, Participants: CEM-102 (Sodium Fusidate) 10
• Clinical Success at 15 Months (Secondary), Count of participants, Participants: CEM-102 (Sodium Fusidate) 8
• Clinical Success at 18 Months (Secondary), Count of participants, Participants: CEM-102 (Sodium Fusidate) 8
• Clinical Success at 21 Months (Secondary), Count of participants, Participants: CEM-102 (Sodium Fusidate) 6
• Clinical Success at 24 Months (Secondary), Count of participants, Participants: CEM-102 (Sodium Fusidate) 7

Adverse events

Time frame: 24 months

Serious adverse events by term

Other adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2017-12-04)

• Robert Dobbins, MD, PhD, Study director, Melinta Therapeutics, Inc.