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

• ClinicalTrials.gov Identifier: NCT03880539
• Recruitment Status: Recruiting
• First Posted: March 19, 2019
• Last Update Posted: September 17, 2019
• Sponsor: University of Kansas Medical Center
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Lisa Clough, University of Kansas Medical Center

Study Description

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: N/A
• 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)
• Actual Study Start Date: June 17, 2019
• Estimated Primary Completion Date: September 30, 2020
• Estimated Study Completion Date: September 30, 2021

Arms and Interventions

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

Outcome Measures

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).

Eligibility Criteria

• 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

Contacts and Locations

Contacts

Contact: Karen Snyder, CCRC; 913-588-8002; ksnyder6@kumc.edu

Locations

United States, Kansas

University of Kansas Medical Center; Recruiting

Kansas City, Kansas, United States, 66160

Contact: Karen Snyder, BA 913-588-8002 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

• Principal Investigator: Lisa A Clough, MD; University of Kansas Medical Center

More Information

• Responsible Party: Lisa Clough, Principal Investigator, University of Kansas Medical Center
• ClinicalTrials.gov Identifier: NCT03880539
• Other Study ID Numbers: Study00143405
• First Posted: March 19, 2019
• Last Update Posted: September 17, 2019
• Last Verified: June 2019

• 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:

Infection; Communicable Diseases; Clostridium Infections; Enterocolitis, Pseudomembranous; Recurrence; Disease Attributes; Pathologic Processes; Gram-Positive Bacterial Infections; Bacterial Infections; Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Vancomycin; Anti-Bacterial Agents; Anti-Infective Agents