Comparison of Ridinilazole Versus Vancomycin Treatment for Clostridium Difficile Infection
Condition: Clostridioides Difficile Infection
MeSH terms: Infections; Communicable Diseases; Clostridium Infections
Intervention: Ridinilazole; Vancomycin
Intervention description: ridinilazole (200 mg bid); vancomycin (125 mg qid)
Intervention MeSH terms: Vancomycin; Ridinilazole; Benzimidazole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: In both arms patients receive the same number of doses per day. Placebo tablets are included to maintain same number and appearance of IP in both arms.
Enrollment: 759.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Clostridioides difficile; Clostridium difficile; C. difficile; C. diff

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 treated 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.

      Ridinilazole plasma concentration will be assessed in a subset of patients.
    

Eligibility 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.