Overview

To Compare Ridinilazole Versus Vancomycin Treatment for Clostridium Difficile Infection

Status:
Active, not recruiting
Trial end date:
2021-11-01
Target enrollment:
0
Participant gender:
All
Summary
Summit is developing ridinilazole as a novel antimicrobial for Clostridioides difficile Infection (CDI), formerly known as Clostridium difficile Infection, with the goal of demonstrating an improved Sustained Clinical Response rate in subjects treated with ridinilazole as compared to subjects with vancomycin. A phase 2 proof of concept study, with vancomycin as comparator, demonstrated these attributes with a comparable safety profile. A high fecal concentration of ridinilazole and little systemic exposure were noted. The rationale for this phase 3 study is to confirm the improvement in sustained clinical response of CDI over vancomycin and to compare the safety and tolerability of ridinilazole to that of vancomycin.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Summit Therapeutics
Treatments:
Vancomycin
Criteria
Inclusion Criteria

Patients are eligible to be included in the study only if all the following criteria apply:

1. Patient must be at least 18 years of age, at the time of signing the informed consent.

2. Have signs and symptoms of CDI including diarrhea such that in the Investigator's
opinion, CDI antimicrobial therapy is required. Diarrhea is defined as a change in
bowel habits, with ≥3 unformed bowel movements (UBMs) (5, 6 or 7 on the Bristol Stool
Chart) in the 24 h prior to randomization.

3. Have the presence of either toxin A and/or B of C. difficile in the stool determined
by a positive free toxin test (using a Sponsor agreed test). The stool sample must be
current (produced within 72 hours prior to randomization).

4. Male or Female

Male patients:

• A male patient must agree to use contraception as detailed in Section 10.4 of this
protocol during the treatment period and for at least 30 days after the last dose of
study treatment and refrain from donating sperm during this period.

Female patients:

• A female patient is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies: i. Not a woman of
childbearing potential (WOCBP) OR ii. A WOCBP who agrees to follow the contraceptive
guidance during the treatment period and for at least 30 days after the last dose of
study treatment.

5. Has provided documented signed informed consent and any authorizations required by
local law (e.g. Protected Health Information [PHI]). If unable to read, understand and
sign the informed consent form a legally authorized representative (LAR) may provide
consent on the patient's behalf if permitted by the Institutional Review Board
(IRB)/Ethics Committee (EC).

Exclusion Criteria

Patients are excluded from the study if any of the following criteria apply:

1. Have had more than one prior episode of CDI in the previous 3 months or more than 3
episodes in the past 12 months prior to randomization.

2. Have a history of chronic diarrheal disease including inflammatory bowel disease
(Crohn's disease or ulcerative colitis).

3. Have had a positive diagnostic test for other GI pathogens, considered to be
clinically relevant, within 2 weeks of randomization.

4. Have had major gastrointestinal (GI) surgery (e.g. significant bowel resection) within
3 months of randomization (this does not include appendectomy). The presence of a
colostomy or ileostomy or likely requirement of an ostomy during the study.

5. Have life threatening or fulminant CDI with evidence of hypotension, septic shock,
peritoneal signs or absence of bowel sounds, or toxic megacolon.

6. History of bone marrow or hematopoietic stem cell transplant at any time or a known
current history of a severely compromised/suppressed immune system that, in the
opinion of the Investigator, would make the patient unsuitable for the study.

7. Have had more than the equivalent of 24 hours of dosing of antimicrobial treatment
active against the current episode of CDI prior to randomization. (i.e. more than four
doses of oral vancomycin, two doses of fidaxomicin or three doses of metronidazole).

8. Prior or current use of anti-toxin antibodies including bezlotoxumab within the past 6
months prior to randomization.

9. Are unable to discontinue products used affecting disease progression at
randomization.

10. Has been involved in a clinical trial and received an investigational medicinal
product for indications other than CDI within 1 month or five half-lives (whichever is
longer) or within 3 months if the investigational medical product was for CDI.

11. Have received an investigational vaccine against C. difficile.

12. Patients that the Investigator feels are inappropriate for the study this would
include those;

1. with any other condition that, in the Investigator's judgment, would make the
patient unsuitable for inclusion in the study.

2. who, in the opinion of the Investigator, are not likely to complete the study for
whatever reason, e.g. short life expectancy.

3. with known hypersensitivity or intolerance to ridinilazole, vancomycin, and/or
their excipients

4. who are unwilling or unable to comply with protocol requirements, e.g. complete
the full course of study treatment per schedule, attend study visits, report
diarrhea/suspected recurrence, provide stool samples, ingest capsules/tablets or
blood draws.