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Bezlotoxumab (BEZLO) In Addition To Standard Of Care (SOC) Vancomycin For The Treatment of Multi-Recurrent Clostridium Difficile Infection (BEZLO)

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ClinicalTrials.gov Identifier: NCT03880539
Recruitment Status : Not yet recruiting
First Posted : March 19, 2019
Last Update Posted : March 19, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Lisa Clough, University of Kansas Medical Center

Brief Summary:
This is a research study to collect information from people that have Clostridium difficile infection (CDI) and are treated with a standard antibiotic treatment in which the antibiotic dose is gradually reduced over 6 weeks and bezlotoxumab (BEZLO), an approved monoclonal antibody targeting C. difficile toxin, which has shown to reduce CID recurrence when used in combination with standard antibiotic treatment.

Condition or disease Intervention/treatment Phase
Clostridium Difficile Infection Recurrence Drug: bezlotoxumab Drug: Vancomycin Oral Phase 4

Detailed Description:
Clostridium difficile (C. diff) is a type of bacteria which causes diarrhea in some people who receive antibiotics for other infections. The current antibiotics used to treat C diff infection (CDI) are usually successful in treating the initial episode of CDI, but may not prevent recurrent infection. To prevent recurrent CDI, standard oral antibiotic treatment with vancomycin is extended by gradually reducing the dose over 4-8 weeks. This is called antibiotic taper. Bezlotoxumab (BEZLO), a monoclonal antibody targeting C. difficile toxin B, is an approved medication that has also been shown to reduce CDI recurrence in patients receiving antibacterial drug treatment of CDI. In this study, approximately 12 people with multi-recurrent CDI will be treated with BEZLO in combination with standard oral tapered vancomycin. Study participation will last 16 weeks. The rate of CDI recurrence in this group will be compared to information collected from approximately 72 historical patients with multi-recurrent CDI treated with oral tapered vancomycin only.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Intervention Model: Single Group Assignment
Intervention Model Description: The intervention group will consist of a single arm of patients treated with BEZLO + SOC oral VAN pulse/taper for multi-recurrent CDI, with a planned enrollment of 12 patients. To achieve the aim of the proposed study, we will compare the efficacy of BEZLO + SOC oral VAN pulse/taper to a historical cohort of patients treated with SOC oral VAN pulse/taper only. These patients will be matched 1:6 on criteria previously outlined in this proposal (BEZLO + SOC, n=12; SOC comparator, n=72; total number of patients in study, n=84).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Historically-controlled Clinical Trial of the Efficacy and Safety of Bezlotoxumab (BEZLO) in Addition to Standard of Care (SOC) Vancomycin for the Treatment of Multi-recurrent Clostridium Difficile Infection (CDI)
Estimated Study Start Date : April 15, 2019
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
BEZLO + SOC taper
Single arm of patients treated with BEZLO + SOC oral VAN pulse/taper.
Drug: bezlotoxumab
Adding BEZLO to SOC oral VAN pulse/taper

Drug: Vancomycin Oral
SOC vancomycin pulse/taper




Primary Outcome Measures :
  1. Rate of CDI reoccurrence at 12 weeks [ Time Frame: 12 weeks ]
    If diarrhea resolves (defined as <2 loose stools per day for at least 2 consecutive days) and subsequently begins again (3 or more loose stools in 24 hours or less for at least 2 consecutive days), this will represent a new episode of diarrhea. If there is a new episode of diarrhea at any time during the 12-week study period, an unscheduled visit will be conducted. A stool sample will be provided for any new episode of diarrhea which occurs and a stool test for toxigenic C. difficile (NAAT plus EIA) will be performed. CDI reoccurrence will be defined as new episode of diarrhea and positive stool test for toxigenic C. difficile (NAAT plus EIA).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (Interventional):

  • i) age 18 years or older;
  • ii) diagnosis of multi-recurrent CDI, defined as passage of 3 or more loose stools in 24 hours or less for at least 2 consecutive days and a positive stool test for toxigenic C. difficile (nucleic acid amplification test [NAAT] and toxin enzyme immunoassay [EIA] positive), with 2 or more confirmed prior CDI episodes;
  • iii) receiving or planning to receive a 10- to 14-day course of SOC therapy with oral VAN followed by a tapered VAN regimen for at least 4 weeks;
  • iv) patient highly unlikely to become pregnant due to being female and not of reproductive potential or female of reproductive potential agreeing to be abstinent or using 2 acceptable methods of birth control starting at enrollment and through the 16-week study period; and
  • v) patient or legal representative voluntarily agreeing to participate by providing written informed consent after the nature of the study has been fully explained.

Inclusion Criteria (Historical Control):

  • i) age 18 years or older
  • ii) diagnosis of multi-recurrent CDI
  • iii) received 10- to 14-day course of SOC therapy with oral VAN followed by a tapered VAN regimen.

Exclusion Criteria:

  • i) active chronic diarrheal illness, such as (but not limited to) ulcerative colitis or Crohn's disease or with a condition such that they routinely pass loose stool
  • ii) planned surgery for CDI within 24 hours
  • iii) positive pregnancy test in the 48 hours before the infusion or unwilling to undergo pregnancy testing if a pre-menopausal female who is not sterilized and therefore has the potential to bear a child
  • iv) breastfeeding or planning to breastfeed prior to the completion of the study period
  • v) previous receipt of BEZLO
  • vi) receipt of immune globulin within 6 months prior to enrollment or planning to receive immune globulin prior to completion of the 16-week study period
  • vii) receipt of non-SOC CDI therapy within 14 days prior to enrollment
  • viii) planned treatment with SOC therapy for longer than 6 weeks
  • ix) receipt of medications to control diarrhea such as loperamide, diphenoxylate hydrochloride/atropine sulfate at any time prior to completion of the 16-week study period
  • x) medical history of decompensated congestive heart failure

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): NCT03880539


Contacts
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Contact: David Bram, RN 913-588-3894 dbram@kumc.edu
Contact: Karen Snyder 913-588-8002 ksnyder6@kumc.edu

Locations
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United States, Kansas
University of Kansas Medical Center Not yet recruiting
Kansas City, Kansas, United States, 66160
Contact: David Bram, RN    913-588-3894    dbram@kumc.edu   
Contact: Karen Snyder, BA    9135888002    ksnyder6@kumc.edu   
Principal Investigator: Lisa A Clough, MD         
Sub-Investigator: Nicholas Britt, PharmD         
Sponsors and Collaborators
University of Kansas Medical Center
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Lisa A Clough, MD University of Kansas Medical Center

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Responsible Party: Lisa Clough, Principal Investigator, University of Kansas Medical Center
ClinicalTrials.gov Identifier: NCT03880539     History of Changes
Other Study ID Numbers: Study00143405
First Posted: March 19, 2019    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Lisa Clough, University of Kansas Medical Center:
C.diff
Clostridium Difficile
recurrence
Bezlotoxumab
CDI

Additional relevant MeSH terms:
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Infection
Communicable Diseases
Recurrence
Clostridium Infections
Disease Attributes
Pathologic Processes
Gram-Positive Bacterial Infections
Bacterial Infections
Vancomycin
Antibodies, Monoclonal
Anti-Bacterial Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs