To Compare Ridinilazole Versus Vancomycin Treatment for Clostridium Difficile Infection

Clostridioides Difficile Infection Clinical Trial

— Ri-CoDIFy 2  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03595566
• Other study ID #: SMT19969/C005
• Status: Completed
• Phase: Phase 3
• Start date: January 28, 2019
• Est. completion date: November 19, 2021

Study information

• Verified date: October 2022
• Source: Summit Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 404
• Est. completion date: November 19, 2021
• Est. primary completion date: November 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Clostridioides Difficile Infection
• Clostridium Infections
• Communicable Diseases
• Infections

Intervention

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

Locations

Country	Name	City	State
Belarus	Gomel Regional Clinical Hospital	Gomel
Belarus	Grodno City Clinical Hospital of Emergency Care	Grodno
Belarus	City Clinical Hospital of Infectious Diseases	Minsk
Belarus	Vitebsk regional clinical infectious diseases hospital	Vitebsk
Belgium	Cliniques Universitaires Saint-Luc, UCL	Bruxelles
Belgium	Hopital Erasme	Bruxelles
Belgium	AZ Maria Middelares	Gent
Belgium	Az St. Lucas	Gent
Belgium	CHU UCL Namur, Intensive Care Unit	Yvoir
Canada	University of Alberta, Division of Gastroenterology	Edmonton	Alberta
Canada	St. Josephs Healthcare	Hamilton	Ontario
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Michael Garron Hospital	Toronto	Ontario
Canada	Diamond Health Care Center	Vancouver	British Columbia
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	Vancouver Island Health Authority, Research and Capacity Building	Victoria	British Columbia
Chile	Clínica Alemana de Santiago	Santiago
Chile	Clínica Las Condes	Santiago
Czechia	Fakultni nemocnice Brno, Klinika infekcnich chorob	Brno
Czechia	Fakultni nemocnice Hradec Kralove, Klinika infekcnich nemoci	Hradec Králové
Czechia	Nemocnice Kyjov, Infekcni oddeleni	Kyjov
Czechia	Krajska nemocnice Liberec	Liberec
Estonia	Ida-Viru Central Hospital	Kohtla-Järve	Ida-Viru
Estonia	North Estonia Medical Centre	Tallinn	Harju
France	Centre Hospitalier Universitaire Grenoble Alpes	Grenoble
France	CHD Vendée	La Roche-sur-Yon
France	Unité de maladies infectieuses - RDJ Ouest - Hôpital Huriez	Lille	Cedex
France	CIC - CHU de Limoges	Limoges
France	Groupe Hospitalier Bretagne Sud Hopital du Scorff	Lorient
France	Hopital Bichat - Claude-Bernard	Paris
France	Hopital Lariboisiere	Paris
France	Hôpital Saint Antoine	Paris
France	Hopital Saint Louis	Paris
France	CH Intercommunal de Cornouaille (CHIC) QUIMPER / MIIS	Quimper
Georgia	JSC Evex medical corporation	Batumi	Adjara
Georgia	JSC"Infectious Diseases, Aids and Clinical Immunology Research Center"	Tbilisi
Georgia	LLC"Aversi Clinic"	Tbilisi
Georgia	LTD "Acad. G. Chapidze Emergency Cardiology Center"	Tbilisi
Georgia	LTD "Israeli-Georgian Medical research Clinic Helsicore"	Tbilisi
Germany	Vivantes Klinikum Spandau	Berlin
Germany	Universitätsklinikum Essen	Essen	NRW
Germany	Universitätsklinikum Köln	Köln	NRW
Germany	Klinikum St. Georg - Klinik für Infektiologie, Tropenmedizin, Nephrologie unfd Rheumatologie	Leipzig
Germany	Stahl	Marburg	Hessen
Germany	Universitätsklinikum Marburg	Marburg
Germany	Universitätsmedizin Rostock	Rostock
Germany	Uni. Klinik Tübingen Innere Medizin I Hepatologische Therapie- und Studienambulanz	Tübingen
Germany	Kliniken Nordoberpfalz AG, Klinikum Weiden	Weiden
Israel	Barzilai Medical Center	Ashkelon	Southern
Israel	Infectious Diseases & Infection Control Unit	Hadera
Israel	Bnai Zion Medical Center	Haifa
Israel	Rambam Health Care Campus, Internal ward A	Haifa
Israel	Hadassah-Hebrew University	Jerusalem
Israel	Meir Medical Center, Infection Diseases Unit	Kfar-Sava	Central
Israel	Rabin Medical Center	Petah-Tikva	Central
Israel	Tel Hashomer Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Latvia	Daugavpils Regional Hospital	Daugavpils
Latvia	Pauls Stradins Clinical University Hospital	Riga
Latvia	Vidzemes Hospital	Valmiera
Lithuania	Respublikine Siauliu ligonine	Šiauliai
Lithuania	Hospital of Lithuanian University of Health Sciences	Kaunas
Lithuania	Hospital of Lithuanian University of Health Sciences Kauno klinikos	Kaunas
Lithuania	Kauno klinikine ligonine	Kaunas
Lithuania	Klaipedos universitetine ligonine	Klaipeda
Lithuania	Inlita, Santara KTC	Vilnius
Mexico	Hospital Civil "Fray Antonio Alcalde	Guadalajara	Jalisco
Mexico	Nuevo Hospital Civil de Guadalajara	Guadalajara	Jalisco
Mexico	Hospital Universitario Dr. Jose Eleuterio Gonzalez	Monterrey	Nuevo Leon
Mexico	Hospital Universitario Dr. José Eleuterio González	Monterrey	Nuevo Leon
Mexico	Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán	Tlalpan	Mexico City
Peru	Hospital Nacional Alberto Sabogal Sologuren	Callao
Peru	Hospital Nacional Edgardo Rebagliati Martins	Jesus Maria	Lima
Peru	Hospital Nacional 2 de Mayo	Lima
Romania	Spitalul Universitar de Urgenta Bucuresti	Bucharest
Romania	Fundatia "Dr. Victor Babes"	Bucuresti
Romania	Institutul National de Boli Infectioase "Prof. Dr. Matei Bals"	Bucuresti
Romania	Institutul Regional de Gastroenterologie si Hepatologie	Cluj-Napoca
Romania	Spitalul Clinic de Boli Infectioase Cluj-Napoca	Cluj-Napoca
Romania	Spitalul Clinic de Boli Infectioase si Pneumoftiziologie	Craiova	Dolj
Spain	Hospital Universitari Germans Trias i Pujol	Badalona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario Virgen de las Nieves	Granada
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Universitari Mutua de Terrassa	Terrassa
Spain	Hospital Universitario Alvaro Cunqeiro	Vigo
United States	PharmaTex Research LLC	Amarillo	Texas
United States	Anne Arundel Medical Center	Annapolis	Maryland
United States	Summit Clinical Research	Athens	Georgia
United States	Emory University School of Medicine	Atlanta	Georgia
United States	St. David's Healthcare Office of Research	Austin	Texas
United States	Tufts Medical Center	Boston	Massachusetts
United States	Clinical Research of Brandon LLC	Brandon	Florida
United States	Montefiore Medical Center	Bronx	New York
United States	University of Chicago	Chicago	Illinois
United States	The Ohio State Wexner Medical Center	Columbus	Ohio
United States	Wright State University and Premier Health Clinical Trials Research Alliance	Dayton	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	Moonshine Research Center Inc	Doral	Florida
United States	Horizon Research Group of Opelousas, LLC	Eunice	Louisiana
United States	MediSphere Medical Research Center, LLC	Evansville	Indiana
United States	DHAT Research Institute	Garland	Texas
United States	Hartford Hospital	Hartford	Connecticut
United States	University of Houston	Houston	Texas
United States	University Texas MD Anderson Cancer Center	Houston	Texas
United States	Snake River Research PLLC	Idaho Falls	Idaho
United States	Western Michigan University Homer Stryker M.D.	Kalamazoo	Michigan
United States	Vidant Multispecialty Clinic - Kinston	Kinston	North Carolina
United States	Vidant Multispecialty Clinic - Kinston, Attn. Research Department	Kinston	North Carolina
United States	EvergreenHealth Medical Center	Kirkland	Washington
United States	Multi-Specialty Research Associates Inc.	Lake City	Florida
United States	Florida Research Institute	Lakewood Ranch	Florida
United States	Sierra Clinical Research	Las Vegas	Nevada
United States	Emeritas Research Group	Leesburg	Virginia
United States	University of CA Los Angeles	Los Angeles	California
United States	Gastrointestinal Specialists Of Georgia	Marietta	Georgia
United States	Advanced Medical Research Institute	Miami	Florida
United States	Coral Research Clinic Corp	Miami	Florida
United States	Jackson Memorial Hospital	Miami	Florida
United States	L&C Professional Medical Research Institute	Miami	Florida
United States	Mount Sinai	New York	New York
United States	Arkansas Gastroenterology	North Little Rock	Arkansas
United States	DiGiovanna Institute For Medical Education	North Massapequa	New York
United States	Sarkis Clinical Trials	Ocala	Florida
United States	Advanced Medical Research Center	Port Orange	Florida
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Guthrie Clinic - Sayre	Sayre	Pennsylvania
United States	Louisiana Res Center LLC	Shreveport	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Summit Therapeutics

Countries where clinical trial is conducted

United States,  Belarus,  Belgium,  Canada,  Chile,  Czechia,  Estonia,  France,  Georgia,  Germany,  Israel,  Latvia,  Lithuania,  Mexico,  Peru,  Romania,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained Clinical Response (SCR) defined as Clinical Response and no recurrence of CDI through 30 days post End of Treatment (EOT).		Day 40
Secondary	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
Secondary	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
Secondary	Sustained Clinical Response over 60 days	defined as Clinical Response and no recurrence of CDI through 60 days post EOT	Day 70
Secondary	Sustained Clinical Response over 90 days	defined as Clinical Response and no recurrence of CDI through 90 days post EOT	Day 100
Secondary	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
Secondary	Change from baseline to EOT of the microbiota a-diversity (Shannon) index in stool samples		Day 10
Secondary	Change from baseline to EOT of the gut microbiota ß-diversity (Bray-Curtis) index in stool samples		Day 10

External 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