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 22, 2020
• 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 22, 2020
• 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: 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) ]

• Original Secondary Outcome Measures: Same as current
• 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) 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: Clostridium 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:

1. At least 18 years of age, at the time of signing the informed consent.
2. 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. The presence of either toxin A and/or B of C. difficile in the stool determined by a positive free toxin test, produced within 72 hours prior to randomization.

4. Male or Female

   • Male must agree to use contraception as detailed in the protocol during the treatment period and for at least 5 days after study treatment and refrain from donating sperm during this period.
   • Female patient is eligible to participate if she is not pregnant, not breastfeeding, and either:

   Not a woman of childbearing potential (WOCBP). A WOCBP who agrees to follow the contraceptive guidance per protocol during the treatment period and for at least 5 days after study treatment.

5. Documented signed informed consent and any authorizations required by local law (e.g. Protected Health Information [PHI]).

Exclusion Criteria:

1. More than one prior episode of CDI in the previous 3 months or more than 3 episodes in the past 12 months.
2. A history of chronic diarrheal disease including inflammatory bowel disease (Crohn's disease or ulcerative colitis).
3. Positive diagnostic test for other gastro intestinal (GI) pathogens within 2 weeks of randomization.
4. Major gastrointestinal (GI) surgery (e.g. significant bowel resection) within 3 months of randomization (except appendectomy). Presence of a colostomy or ileostomy or likely requirement of an ostomy during the study.
5. Life threatening or fulminant CDI with evidence of hypotension, septic shock, peritoneal signs or absence of bowel sounds, or toxic megacolon.

6. Current history of significantly compromised immune system e.g.:

   1. HIV positive with a CD4<200 cells/mm3 within 6 months of randomization.
   2. Severe neutropenia with neutrophil count < 500 cells/mL.
   3. Concurrent immunosuppressive therapy for recent (within previous 6 months) or anticipated solid organ transplant or bone marrow transplant.
   4. Concurrent chemotherapy, radiotherapy or biologic for active malignancy. Or active malignancy with ablative chemotherapy within the past 3 months or anticipated during the study.
7. More than one day (24 hours) of dosing of antimicrobial treatment active against CDI for the current episode of CDI prior to randomization.
8. Prior or current use of anti-toxin antibodies including bezlotoxumab.
9. Unable to discontinue products used to affect bowel movement or disease progression.
10. Involved in a clinical trial and received an IMP for indications other than CDI within 1 month or five half-lives (whichever is longer) or within 3 months if the IMP was for CDI.
11. Received an investigational vaccine against C.difficile.
12. Patients that the Investigator feels are inappropriate for the study for any other reason e.g. have any conditions that would make the patient unsuitable for inclusion, patients not likely to complete the study for whatever reason, known hypersensitivity or intolerance to study IMPs, patients unwilling or unable to comply with protocol requirements

Sex/Gender

• Sexes Eligible for Study: All

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

Contacts

Contact: Lauren Kuhn; 001 617 225 4464; lauren.kuhn@summitplc.com

Contact: Winnie Barlow; 01235 443939; winnie.barlow@summitplc.com

• Listed Location Countries: Belarus, Belgium, Czechia, Estonia, Georgia, Germany, Israel, Latvia, Peru, 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: Richard Vickers, PhD; Summit (Oxford)Limited

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