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

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ClinicalTrials.gov Identifier: NCT02436876
Recruitment Status : Active, not recruiting
First Posted : May 7, 2015
Last Update Posted : August 13, 2018
Sponsor:
Collaborators:
University of Pennsylvania
University of California, San Francisco
Medpace, Inc.
Congressionally Directed Medical Research Programs
Information provided by (Responsible Party):
Microbion Corporation

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 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
Study Start Date : January 2016
Estimated Primary Completion Date : September 1, 2018
Estimated Study Completion Date : December 31, 2018

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Number of Participants with Changes in Clinical Laboratory Tests, Vital Signs, Physical Exams, Electrocardiograms, Microbiology Status, Treatment Failures and/or Adverse Events as a composite to measure Safety and Tolerability [ Time Frame: 24 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 Serious Interventions Required Post-Treatment to Eradicate Infection [ Time Frame: 24 weeks ]
    The cumulative number of serious interventions and treatment failures will be measured and compared to the placebo arm, following administration of MBN-101 or placebo, to evaluate the clinical activity of single, escalating doses of locally administered MBN-101.

  2. Time to First Serious Intervention [ Time Frame: Up to 24 weeks ]
    Time to first necessary treatment intervention following administration of MBN-101 or placebo will be assessed.

  3. Composite Pharmacokinetics of Single Escalating Doses of Locally Administered MBN-101 [ Time Frame: 1, 6, 12, 24, 36, 48, 60, 72, 96, and 336 hr post-dose ]

    Whole blood concentrations will be measured after administration of single escalating doses of MBN-101 and will be used to calculate pharmacokinetic parameters [i.e.:

    • Tmax (time of the maximum observed concentration)
    • Cmax (peak drug concentration)
    • AUC (area under the plasma-concentration time curve)
    • T1/2 (terminal half-life)
    • CL/F (extravascular clearance), and
    • Vz/F (extravascular volume of distribution)].

  4. Time to Fracture Healing and Removal of Orthopedic Hardware Post-Treatment [ Time Frame: Up to 24 weeks ]
    Time to fracture healing and removal of orthopedic hardware will be measured to assess treatment efficacy



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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02436876


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

Responsible Party: Microbion Corporation
ClinicalTrials.gov Identifier: NCT02436876     History of Changes
Other Study ID Numbers: MBN-101-201
W81XWH-12-2-0100 ( Other Grant/Funding Number: CDMRP )
First Posted: May 7, 2015    Key Record Dates
Last Update Posted: August 13, 2018
Last Verified: August 2018

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