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

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.

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