Study to Assess Safety and Clinical Activity of Local MBN-101 in Treatment of Infected Bone Sites

Study Overview
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Brief Summary
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This study evaluates the safety and clinical benefit of MBN-101 administered intraoperatively to osteosynthesis or osteomyelitis sites for patients diagnosed with an orthopedic infection, with or without orthopaedic hardware. Three quarters of the patients will receive MBN-101, while the other one quarter will receive placebo.

Detailed Description
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Postoperative orthopaedic infections, particularly antibiotic-resistant infections, present a serious clinical challenge to surgeons and other treating physicians. These infections frequently involve implanted foreign materials (stabilizing orthopaedic hardware), making infection of these sites much more likely than if foreign materials were not involved. MBN-101 has broad spectrum antimicrobial activity against orthopaedic wound pathogens. This is a randomized, single-blind, placebo-controlled, multi-center study to assess the safety and tolerability of escalating doses of MBN-101 to treat orthopaedic infections during revision surgery, (a) with or without orthopaedic hardware, and (b) with or without removal and replacement of orthopaedic hardware.

Official Title
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Phase 2a Randomized, Single-Blind, Placebo-Controlled, 12-week Escalating Dose Study to Assess the Safety, Tolerability and Clinical Activity of 3 Concentrations of Locally Applied MBN-101 to Infected Bone Sites

Conditions
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Bacterial Infection

Intervention / Treatment
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* Drug: MBN-101
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be eligible for this study, each of the following criteria must be satisfied with a YES answer (unless not applicable): Patients who: have had operative fracture fixation of the upper extremity (AO/OTA class 15, 11-13, 21-23), lower extremity (AO/OTA class 31-34, 41 44, 81, 82) or pelvis (61, 62), or have undergone arthrodesis, and have subsequently been diagnosed with an apparent fracture site infection or are diagnosed with chronic or acute-on-chronic osteomyelitis of the long bone extremities (including residual amputated limbs) have at least one of the following: require surgical debridement of infected soft tissue and/or bone, with or without removal and/or placement/replacement of hardware male or female between the ages of 18 and 75 at the time the ICF is reviewed and signed patients receiving or anticipated to receive systemic antibiotic therapy as per institution's standard of care patients requiring postoperative hospitalization for at least 48 hours after revision surgery have read and signed the Informed Consent Form (ICF) after the nature of the study has been fully explained be willing and able to provide authorization for use and disclosure of personal health information in accordance with the Health Insurance Portability and Accountability Act (HIPAA) Exclusion Criteria: To be eligible for this study, each of the following criteria must be satisfied with a NO answer (unless not applicable): Patients who are no longer hardware dependent or are definitively treated for their infection by hardware removal without replacement Patients with multiple, non-contiguous sites of infection Pathologic fracture (not including osteoporosis) Patient requires immunosuppressive therapy (Topical or inhaled corticosteroids are permitted) Serum creatinine, ALT, AST or Alkaline Phosphatase >2.0 times the upper limit of the normal range of the local testing laboratory Absolute neutrophil count <1000 Patients without definitive soft-tissue coverage over the surgical site at time of study product administration Any condition that has required treatment with any other bismuth containing compound within the last 2 weeks (i.e., Kaopectate or Pepto Bismol) Participation in an investigational trial to evaluate pharmaceuticals or biologics within the past 3 months Individuals undergoing surgical treatment for more than one infected site Patients who are pregnant, lactating, or female patients who have a positive serum hCG (human Chorionic Gonadotropin) as determined by laboratory testing Immunocompromised due to illness or organ transplant History of chronic or recurrent infections (≥ 3 infections at the same site within 12 months) History of any type of cancer (excluding non-melanomatous localized skin cancer or completely excised and cured carcinoma-in-situ of uterine cervix) Poorly controlled diabetes mellitus History of medical noncompliance Other medical conditions which, in the opinion of the Principal Investigator, would jeopardize the safety of the study subject or impact the validity of the study results. Current incarceration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Single, intra-wound local administration of MBN-101; dosage = 0.5 µg/cm2; randomized 3:1 with placebo | Drug: MBN-101<br>* MBN-101 is a locally administered, anti-infective drug product<br>* Other names: MBN-101 Drug Product;Other: Placebo<br>* The placebo is comprised of the vehicle/excipients used to formulate MBN-101, but does not contain the active pharmaceutical ingredient<br>* Other names: Diluent; Vehicle;|
| Experimental: Cohort 2<br>Single, intra-wound local administration of MBN-101; dosage = 1.5 µg/cm2; randomized 3:1 with placebo | Drug: MBN-101<br>* MBN-101 is a locally administered, anti-infective drug product<br>* Other names: MBN-101 Drug Product;Other: Placebo<br>* The placebo is comprised of the vehicle/excipients used to formulate MBN-101, but does not contain the active pharmaceutical ingredient<br>* Other names: Diluent; Vehicle;|
| Experimental: Cohort 3<br>Single, intra-wound local administration of MBN-101; dosage = 5.0 µg/cm2; randomized 3:1 with placebo | Drug: MBN-101<br>* MBN-101 is a locally administered, anti-infective drug product<br>* Other names: MBN-101 Drug Product;Other: Placebo<br>* The placebo is comprised of the vehicle/excipients used to formulate MBN-101, but does not contain the active pharmaceutical ingredient<br>* Other names: Diluent; Vehicle;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | This study evaluates the safety and tolerability of single escalating doses of locally administered MBN-101 or placebo, as adjunct to standard of care antimicrobial and surgical therapy. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment Failures | Treatment failure is defined as clinical course requiring additional infection-related interventions including rehospitalization, additional surgery, or additional courses of systemic antibiotics. | 12 weeks | 
| Treatment Failure in Subjects With Antibiotic-resistant Infections | Treatment failure in subjects with baseline infections resistant to one or more antibiotics based on Central Laboratory Microbiological data | Up to 12weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteosynthesis, Complications, Infection or Inflammation, Orthopedic, Device, Fracture, Osteomyelitis