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

• ClinicalTrials.gov Identifier: NCT02436876
• Recruitment Status: Completed
• First Posted: May 7, 2015
• Results First Posted: September 30, 2021
• Last Update Posted: September 30, 2021
• Sponsor: Microbion Corporation
• Collaborators: University of Pennsylvania; University of California, San Francisco; Medpace, Inc.; Congressionally Directed Medical Research Programs
• Information provided by (Responsible Party): Microbion Corporation

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Bacterial Infection	Drug: MBN-101; Other: Placebo	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 24, 2016
• Actual Primary Completion Date: October 27, 2017
• Actual Study Completion Date: July 26, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adverse Events [ Time Frame: 12 weeks ]
   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.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Orthopedic Trauma Institute, University of California San Francisco

San Francisco, California, United States, 94110

UCSF - Parnassus

San Francisco, California, United States, 94143

United States, Maryland

LifeBridge Health, Inc.

Baltimore, Maryland, United States, 21215

United States, Ohio

OhioHealth Research Institute

Columbus, Ohio, United States, 443215

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Texas

The University of Texas - Health Science Center & Medical School at Houston

Houston, Texas, United States, 77030

Sponsors and Collaborators

Microbion Corporation

University of Pennsylvania

University of California, San Francisco

Medpace, Inc.

Congressionally Directed Medical Research Programs

Investigators

• Study Chair: Brett Baker, MSc, DC; Microbion Corporation

  Study Documents (Full-Text)

Documents provided by Microbion Corporation:

Study Protocol  [PDF] December 13, 2017

Statistical Analysis Plan  [PDF] July 19, 2018

More Information

• Responsible Party: Microbion Corporation
• ClinicalTrials.gov Identifier: NCT02436876
• Other Study ID Numbers: MBN-101-201; W81XWH-12-2-0100 ( Other Grant/Funding Number: CDMRP )
• First Posted: May 7, 2015
• Results First Posted: September 30, 2021
• Last Update Posted: September 30, 2021
• Last Verified: September 2021

• Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by Microbion Corporation:

Osteosynthesis; Complications; Infection or Inflammation; Orthopedic; Device; Fracture; Osteomyelitis

Additional relevant MeSH terms:

Bacterial Infections; Infections; Bacterial Infections and Mycoses