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

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

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02569541

Enrollment

Registered

2015-10-06

Start date

2015-12-31

Completion date

2019-02-21

Last updated

2020-01-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Refractory Bone or Joint Infections

Keywords

fusidic acid, prosthetic joint infections, bone infections, osteomyelitis

Brief summary

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

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).

Interventions

DRUGsodium fusidate

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

12 Years to No maximum

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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
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 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
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

Countries

United States

Participant flow

Participants by arm

Arm	Count
CEM-102 (Sodium Fusidate) 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) sodium fusidate	30
Total	30

Baseline characteristics

Characteristic	CEM-102 (Sodium Fusidate)
Age, Continuous	61 years STANDARD_DEVIATION 13.4
Baseline Pathogen coagulase-negative Staphylococcus	3 Participants
Baseline Pathogen Corynebacterium striatum/simulans	2 Participants
Baseline Pathogen Cutibacterium acnes	1 Participants
Baseline Pathogen Staphylococcus aureus (MRSA)	10 Participants
Baseline Pathogen Staphylococcus aureus (MSSA)	12 Participants
Baseline Pathogen Staphylococcus epidermidis	4 Participants
Baseline Pathogen Streptococcus agalactiae	1 Participants
BMI	28.7 kg/m2 STANDARD_DEVIATION 6.79
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Height	174.5 cm STANDARD_DEVIATION 11.54
Infection Type and Location Chronic septic arthritis - knee	1 Participants
Infection Type and Location Osteomyelitis	4 Participants
Infection Type and Location Other orthopedic hardware	5 Participants
Infection Type and Location Prosthetic joint infection - hip	4 Participants
Infection Type and Location Prosthetic joint infection - knee	11 Participants
Infection Type and Location Prosthetic joint infection - other	4 Participants
Infection Type and Location Prosthetic joint infection - shoulder	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	2 Participants
Race (NIH/OMB) More than one race	1 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	27 Participants
Region of Enrollment United States	30 participants
Risk Factors for BJI Decubitis ulcers from Immobility	4 Participants
Risk Factors for BJI Diabetes Mellitis	8 Participants
Risk Factors for BJI Previous PJI in Another Anatomical Location	4 Participants
Risk Factors for BJI Rheumatoid Arthritis	3 Participants
Sex: Female, Male Female	10 Participants
Sex: Female, Male Male	20 Participants
Weight	87.4 kg STANDARD_DEVIATION 22.12

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 30
other Total, other adverse events	27 / 30
serious Total, serious adverse events	15 / 30

Outcome results

Primary

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

Time frame: 6 months after start of treatment