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

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

Study Overview

• Status: Completed
• Conditions: Refractory Bone or Joint Infections
• Intervention / Treatment: Drug: sodium fusidate

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).

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Fountain Valley, California, United States, 92708
    • San Dimas, California, United States, 91773
    • Sylmar, California, United States, 91432
    • Torrance, California, United States, 90502
  • Florida
    • Tamarac, Florida, United States, 33321
  • Illinois
    • Springfield, Illinois, United States, 62703
  • Kentucky
    • Louisville, Kentucky, United States, 40202
  • Maryland
    • Baltimore, Maryland, United States, 21218
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
  • Michigan
    • Detroit, Michigan, United States, 48202
  • Montana
    • Butte, Montana, United States, 59701
  • New Jersey
    • Somers Point, New Jersey, United States, 08244
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
  • Ohio
    • Cincinnati, Ohio, United States, 45219
    • Cleveland, Ohio, United States, 44195
  • Pennsylvania
    • Haverford, Pennsylvania, United States, 19041
    • Malvern, Pennsylvania, United States, 19355
    • Philadelphia, Pennsylvania, United States, 19107
  • Texas
    • Houston, Texas, United States, 77030

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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)	Drug: sodium fusidate; Other Names: fusidic acid; CEM-102

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Arrevus Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): October 17, 2017
• Study Completion (Actual): February 21, 2019

Study Registration Dates

• First Submitted: October 5, 2015
• First Submitted That Met QC Criteria: October 5, 2015
• First Posted (Estimate): October 6, 2015

Study Record Updates

• Last Update Posted (Actual): January 30, 2020
• Last Update Submitted That Met QC Criteria: January 21, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: osteomyelitis; fusidic acid; prosthetic joint infections; bone infections
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Joint Diseases; Musculoskeletal Diseases; Arthritis; Infections; Communicable Diseases; Arthritis, Infectious; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Fusidic Acid
• Other Study ID Numbers: CE06-302

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