To Compare Ridinilazole Versus Vancomycin Treatment for Clostridium Difficile Infection (Ri-CoDIFy 2)

• ClinicalTrials.gov Identifier: NCT03595566
• Recruitment Status: Recruiting
• First Posted: July 23, 2018
• Last Update Posted: January 28, 2021
• Sponsor: Summit Therapeutics
• Information provided by (Responsible Party): Summit Therapeutics

Tracking Information

• First Submitted Date: June 11, 2018
• First Posted Date: July 23, 2018
• Last Update Posted Date: January 28, 2021
• Actual Study Start Date: January 28, 2019
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 11, 2018): Sustained clinical response defined as clinical cure at the Assessment of Cure (AOC) visit and no recurrence of CDI within 30 days post end of treatment (EOT) [ Time Frame: Day 40 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 25, 2021)

• Clinical cure at Assessment of Cure (AOC) visit [ Time Frame: Day 12 ]
• Sustained clinical response over 60 days [ Time Frame: Day 70 ]
  defined as clinical cure at the AOC visit and no recurrence of CDI within 60 days post EOT
• Sustained clinical response over 90 days [ Time Frame: Day 100 ]
  defined as clinical cure at the AOC visit and no recurrence of CDI within 90 days post EOT
• Investigator assessment of clinical cure at the AOC visit [ Time Frame: Day 12 ]
• Investigator assessment of sustained clinical response at 30, 60- and 90-days post EOT [ Time Frame: Days 40, 70 and 100 ]
• Relative abundance and diversity of the microbiome and bile salt composition in fecal samples at the end of treatment [ Time Frame: Day 1 to Day 40 ]

Original Secondary Outcome Measures (submitted: July 11, 2018)

• Clinical cure at Assessment of Cure (AOC) visit [ Time Frame: Day 12 ]
• Sustained clinical response over 60 days [ Time Frame: Day 70 ]
• Sustained clinical response over 90 days [ Time Frame: Day 100 ]
• Incidence of treatment related adverse events as per CTCAE v4.0 [ Time Frame: From Day 1 to Day 100 (end of study) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: To Compare Ridinilazole Versus Vancomycin Treatment for Clostridium Difficile Infection
• Official Title: A Phase 3, Randomized, Double-blind, Active Controlled Study to Compare the Efficacy and Safety of Ridinilazole (200 mg, Bid) for 10 Days With Vancomycin (125 mg, Qid) for 10 Days in the Treatment of Clostridium Difficile Infection (CDI)

Brief Summary

Summit is developing ridinilazole as a novel antimicrobial for Clostridium difficile Infection (CDI), formerly known as Clostridium difficile Infection, with the goal of achieving comparable cure rates to standard of care, but reducing rates of recurrent disease.

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

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 the same number and appearance of IP in both arms.

Primary Purpose: Treatment

• Condition: Clostridioides Difficile Infection

Intervention

• Drug: ridinilazole
  ridinilazole 200mg bid
• Drug: vancomycin
  vancomycin 125mg qid

Study Arms

• Experimental: ridinilazole
  Intervention: Drug: ridinilazole
• Active Comparator: vancomycin
  Intervention: Drug: vancomycin

• Publications *: Carlson TJ, Endres BT, Bassères E, Gonzales-Luna AJ, Garey KW. Ridinilazole for the treatment of Clostridioides difficile infection. Expert Opin Investig Drugs. 2019 Apr;28(4):303-310. doi: 10.1080/13543784.2019.1582640. Epub 2019 Feb 26. Review.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 11, 2018): 680
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2021
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Mary Alvarado; +1 617 401 3341; mary.alvarado@summitplc.com

• Listed Location Countries: Belarus, Belgium, Canada, Chile, Czechia, Estonia, France, Georgia, Germany, Israel, Latvia, Lithuania, Mexico, Peru, Romania, Spain, United States

Administrative Information

• NCT Number: NCT03595566
• Other Study ID Numbers: SMT19969/C005
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Summit Therapeutics
• Study Sponsor: Summit Therapeutics
• Collaborators: Not Provided

Investigators

• Study Director: Jos Houbiers, MD, PhD; Summit Therapeutics

• PRS Account: Summit Therapeutics
• Verification Date: July 2020