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

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)

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.

Study Overview

• Status: Completed
• Conditions: Clostridioides Difficile Infection
• Intervention / Treatment: Drug: ridinilazole; Drug: vancomycin

• Study Type: Interventional
• Enrollment (Actual): 404
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Gomel, Belarus, 246029
    • Gomel Regional Clinical Hospital
  • Grodno, Belarus, 230027
    • Grodno City Clinical Hospital of Emergency Care
  • Minsk, Belarus, 220002
    • City Clinical Hospital of Infectious Diseases
  • Vitebsk, Belarus, 210009
    • Vitebsk regional clinical infectious diseases hospital
• Belgium
  • Bruxelles, Belgium, 1070
    • Hopital Erasme
  • Bruxelles, Belgium, 1200
    • Cliniques universitaires Saint-Luc, UCL
  • Gent, Belgium, 9000
    • AZ Maria Middelares
  • Gent, Belgium, 9000
    • AZ St. Lucas
  • Yvoir, Belgium, 5530
    • CHU UCL Namur, Intensive Care Unit
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2X8
      • University of Alberta, Division of Gastroenterology
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Diamond Health Care Center
    • Victoria, British Columbia, Canada, V8R 1J8
      • Vancouver Island Health Authority, Research and Capacity Building
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Josephs Healthcare
    • Toronto, Ontario, Canada, M4C- 3E7
      • Michael Garron Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• Chile
  • Santiago, Chile, 7591047
    • Clinica Las Condes
  • Santiago, Chile, 7650567
    • Clinica Alemana de Santiago
• Czechia
  • Brno, Czechia, 625 00
    • Fakultni nemocnice Brno, Klinika infekcnich chorob
  • Hradec Králové, Czechia, 50005
    • Fakultni nemocnice Hradec Kralove, Klinika infekcnich nemoci
  • Kyjov, Czechia, 69701
    • Nemocnice Kyjov, Infekcni oddeleni
  • Liberec, Czechia, 460 63
    • Krajska Nemocnice Liberec
• Estonia
  • Harju
    • Tallinn, Harju, Estonia, 13419
      • North Estonia Medical Centre
  • Ida-Viru
    • Kohtla-Järve, Ida-Viru, Estonia, 31025
      • Ida-Viru Central Hospital
• France
  • Grenoble, France, 38043
    • Centre Hospitalier Universitaire Grenoble Alpes
  • La Roche-sur-Yon, France, 85925
    • CHD Vendée
  • Limoges, France, 87042
    • CIC - CHU de Limoges
  • Lorient, France, 56322
    • Groupe Hospitalier Bretagne Sud Hopital du Scorff
  • Paris, France, 75010
    • Hôpital Saint Louis
  • Paris, France, 75012
    • Hôpital Saint Antoine
  • Paris, France, 75475
    • Hopital Lariboisiere
  • Paris, France, 75018
    • Hôpital Bichat - Claude-Bernard
  • Quimper, France, 29107
    • CH Intercommunal de Cornouaille (CHIC) QUIMPER / MIIS
  • Cedex
    • Lille, Cedex, France, 59037
      • Unité de maladies infectieuses - RDJ Ouest - Hôpital Huriez
• Georgia
  • Tbilisi, Georgia, 0112
    • LTD "Israeli-Georgian Medical research Clinic Helsicore"
  • Tbilisi, Georgia, 0159
    • LTD "Acad. G. Chapidze Emergency Cardiology Center"
  • Tbilisi, Georgia, 0160
    • JSC"Infectious Diseases, Aids and Clinical Immunology Research Center"
  • Tbilisi, Georgia, 0160
    • LLC"Aversi Clinic"
  • Adjara
    • Batumi, Adjara, Georgia, 6010
      • JSC Evex Medical Corporation
• Germany
  • Berlin, Germany, 13585
    • Vivantes Klinikum Spandau
  • Leipzig, Germany, 04129
    • Klinikum St. Georg - Klinik für Infektiologie, Tropenmedizin, Nephrologie unfd Rheumatologie
  • Marburg, Germany, 35043
    • Universitätsklinikum Marburg
  • Rostock, Germany, 18057
    • Universitatsmedizin Rostock
  • Tübingen, Germany, 72076
    • Uni. Klinik Tübingen Innere Medizin I Hepatologische Therapie- und Studienambulanz
  • Weiden, Germany, 92637
    • Kliniken Nordoberpfalz AG, Klinikum Weiden
  • Hessen
    • Marburg, Hessen, Germany, 35043
      • Stahl
  • NRW
    • Essen, NRW, Germany, 45147
      • Universitätsklinikum Essen
    • Köln, NRW, Germany, 50937
      • Universitätsklinikum Köln
• Israel
  • Hadera, Israel, 38100
    • Infectious Diseases & Infection Control Unit
  • Haifa, Israel, 31048
    • Bnai Zion Medical Center
  • Haifa, Israel, 31096
    • Rambam Health Care Campus, Internal ward A
  • Jerusalem, Israel, 91120
    • Hadassah-Hebrew University
  • Ramat Gan, Israel, 5266202
    • Tel Hashomer Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
  • Central
    • Kfar-Sava, Central, Israel, 4428162
      • Meir Medical Center, Infection Diseases Unit
    • Petah-Tikva, Central, Israel, 49100
      • Rabin Medical Center
  • Southern
    • Ashkelon, Southern, Israel, 7830604
      • Barzilai Medical Center
• Latvia
  • Daugavpils, Latvia, 5417
    • Daugavpils Regional Hospital
  • Riga, Latvia, LV-1002
    • Pauls Stradins Clinical University Hospital
  • Valmiera, Latvia, 4201
    • Vidzemes Hospital
• Lithuania
  • Kaunas, Lithuania, 50161
    • Hospital of Lithuanian University of Health Sciences
  • Kaunas, Lithuania, 50161
    • Hospital of Lithuanian University of Health Sciences Kauno Klinikos
  • Kaunas, Lithuania, 47144
    • Kauno klinikine ligonine
  • Klaipėda, Lithuania, 92288
    • Klaipedos Universitetine Ligonine
  • Vilnius, Lithuania, 08406
    • Inlita, Santara KTC
  • Šiauliai, Lithuania, 76231
    • Respublikine Siauliu Ligonine
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Hospital Civil "Fray Antonio Alcalde
    • Guadalajara, Jalisco, Mexico, 44340
      • Nuevo Hospital Civil de Guadalajara
  • Mexico City
    • Tlalpan, Mexico City, Mexico, 14080
      • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Hospital Universitario Dr. Jose Eleuterio Gonzalez
• Peru
  • Callao, Peru, 7016
    • Hospital Nacional Alberto Sabogal Sologuren
  • Lima, Peru, 15003
    • Hospital Nacional 2 de Mayo
  • Lima
    • Jesus Maria, Lima, Peru, 15072
      • Hospital Nacional Edgardo Rebagliati Martins
• Romania
  • Bucharest, Romania, 050098
    • Spitalul Universitar de Urgență București
  • Bucuresti, Romania, 030303
    • Fundatia "Dr. Victor Babes"
  • Bucuresti, Romania, 21105
    • Institutul National de Boli Infectioase "Prof. Dr. Matei Bals"
  • Cluj-Napoca, Romania, 400000
    • Spitalul Clinic de Boli Infectioase Cluj-Napoca
  • Cluj-Napoca, Romania, 400158
    • Institutul Regional de Gastroenterologie si Hepatologie
  • Dolj
    • Craiova, Dolj, Romania, 200515
      • Spitalul Clinic de Boli Infecţioase şi Pneumoftiziologie
• Spain
  • Badalona, Spain, 08916
    • Hospital Universitari Germans Trias I Pujol
  • Barcelona, Spain, 08003
    • Hospital Del Mar
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de Las Nieves
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Majadahonda, Spain, 28222
    • Hospital Universitario Puerta de Hierro Majadahonda
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Terrassa, Spain, 08221
    • Hospital Universitari Mutua de Terrassa
  • Vigo, Spain, 36312
    • Hospital Universitario Alvaro Cunqeiro
• United States
  • Arkansas
    • North Little Rock, Arkansas, United States, 72117
      • Arkansas Gastroenterology
  • California
    • Los Angeles, California, United States, 90095
      • University of CA Los Angeles
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
  • Florida
    • Brandon, Florida, United States, 33511
      • Clinical Research of Brandon LLC
    • Doral, Florida, United States, 33166
      • Moonshine Research Center Inc
    • Lake City, Florida, United States, 32055
      • Multi-Specialty Research Associates Inc.
    • Lakewood Ranch, Florida, United States, 34211
      • Florida Research Institute
    • Miami, Florida, United States, 33136
      • Jackson Memorial Hospital
    • Miami, Florida, United States, 33174
      • Advanced Medical Research Institute
    • Miami, Florida, United States, 33144
      • L&C Professional Medical Research Institute
    • Miami, Florida, United States, 33186
      • Coral Research Clinic Corp
    • Ocala, Florida, United States, 34474
      • Sarkis Clinical Trials
    • Port Orange, Florida, United States, 32127
      • Advanced Medical Research Center
  • Georgia
    • Athens, Georgia, United States, 30607
      • Summit Clinical Research
    • Atlanta, Georgia, United States, 30322-1013
      • Emory University School of Medicine
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Snake River Research PLLC
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Indiana
    • Evansville, Indiana, United States, 47714
      • MediSphere Medical Research Center, LLC
  • Louisiana
    • Eunice, Louisiana, United States, 70535
      • Horizon Research Group of Opelousas, LLC
    • Shreveport, Louisiana, United States, 71105
      • Louisiana Res Center LLC
  • Maryland
    • Annapolis, Maryland, United States, 21404
      • Anne Arundel Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Kalamazoo, Michigan, United States, 49008
      • Western Michigan University Homer Stryker M.D.
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Sierra Clinical Research
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai
    • North Massapequa, New York, United States, 11758
      • Digiovanna Institute For Medical Education
  • North Carolina
    • Kinston, North Carolina, United States, 28501
      • Vidant Multispecialty Clinic - Kinston, Attn. Research Department
    • Kinston, North Carolina, United States, 28501
      • Vidant Multispecialty Clinic - Kinston
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State Wexner Medical Center
    • Dayton, Ohio, United States, 45409
      • Wright State University and Premier Health Clinical Trials Research Alliance
  • Pennsylvania
    • Sayre, Pennsylvania, United States, 18840
      • Guthrie Clinic - Sayre
  • Texas
    • Amarillo, Texas, United States, 79106
      • PharmaTex Research LLC
    • Austin, Texas, United States, 78705
      • St. David's Healthcare Office of Research
    • Garland, Texas, United States, 75044
      • DHAT Research Institute
    • Houston, Texas, United States, 77030
      • University of Houston
    • Houston, Texas, United States, 77030
      • University Texas MD Anderson Cancer Center
  • Virginia
    • Leesburg, Virginia, United States, 21076
      • Emeritas Research Group
  • Washington
    • Kirkland, Washington, United States, 98034
      • EvergreenHealth Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: vancomycin	Drug: vancomycin; vancomycin 125mg qid
Experimental: ridinilazole	Drug: ridinilazole; ridinilazole 200mg bid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Sustained Clinical Response (SCR) defined as Clinical Response and no recurrence of CDI through 30 days post End of Treatment (EOT).	Day 40

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Cure	defined as the resolution of diarrhea (<3 UBMs in the 1-day period immediately prior to EOT, that is maintained for 2 days after EOT).	Day 12
Sustained Clinical Response over 60 days	defined as Clinical Response and no recurrence of CDI through 60 days post EOT	Day 70
Sustained Clinical Response over 90 days	defined as Clinical Response and no recurrence of CDI through 90 days post EOT	Day 100
Change from baseline to EOT of the relative abundance of the 3 main bile acid groups (conjugated primary, primary and secondary bile acids)		Day 10
Change from baseline to EOT of the microbiota α-diversity (Shannon) index in stool samples		Day 10
Change from baseline to EOT of the gut microbiota β-diversity (Bray-Curtis) index in stool samples		Day 10
Clinical Response	defined as less than 3 unformed bowel movements (UBMs) for 2 consecutive days and maintained through EOT without further CDI treatment at EOT + 2 days, or the investigator's assessment that the subject no longer needs specific CDI antimicrobial treatment after completion of the course of study medication.	Day 12

Collaborators and Investigators

• Sponsor: Summit Therapeutics
• Investigators: Study Director: Lori Styles, MD, Summit Therapeutics

Publications and helpful links

General Publications

• Carlson TJ, Endres BT, Basseres 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.

Helpful Links

• Metagenomic Analysis of the Differential Impact of Ridinilazole and Vancomycin on the Gut Microbiota in a Phase 2 Study
• Ridinilazole, a narrow spectrum antibiotic for treatment of Clostridioides difficile infection, enhances preservation of microbiota-dependent bile acids

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2019
• Primary Completion (Actual): November 19, 2021
• Study Completion (Actual): November 19, 2021

Study Registration Dates

• First Submitted: June 11, 2018
• First Submitted That Met QC Criteria: July 11, 2018
• First Posted (Actual): July 23, 2018

Study Record Updates

• Last Update Posted (Actual): October 13, 2022
• Last Update Submitted That Met QC Criteria: October 11, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Clostridium difficile; C. difficile; C. diff; Clostridioides difficile
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Clostridium Infections; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: SMT19969/C005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No