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

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)

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.

Study Overview

• Status: Completed
• Conditions: Clostridium Difficile Infection Recurrence
• Intervention / Treatment: Drug: bezlotoxumab; Drug: Vancomycin Oral

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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; Other Names: Zinplava; Drug: Vancomycin Oral; SOC vancomycin pulse/taper; Other Names: Firvanq

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of CDI reoccurrence at 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).	12 weeks

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Lisa A Clough, MD, University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2019
• Primary Completion (Actual): November 18, 2021
• Study Completion (Actual): November 18, 2021

Study Registration Dates

• First Submitted: March 11, 2019
• First Submitted That Met QC Criteria: March 14, 2019
• First Posted (Actual): March 19, 2019

Study Record Updates

• Last Update Posted (Actual): May 26, 2022
• Last Update Submitted That Met QC Criteria: May 22, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: recurrence; C.diff; Clostridium Difficile; Bezlotoxumab; CDI
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Recurrence; Clostridium Infections; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: Study00143405

Drug and device information, study documents

• 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