Comparison of Ridinilazole Versus Vancomycin Treatment for Clostridium Difficile Infection

Clostridioides Difficile Infection Clinical Trial

— Ri-CoDIFy 1  

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: NCT03595553
• Other study ID #: SMT19969/C004
• Status: Completed
• Phase: Phase 3
• Start date: January 28, 2019
• Est. completion date: November 17, 2021

Study information

• Verified date: March 2023
• 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 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.

Other known NCT identifiers

• NCT03595566

Recruitment information / eligibility

• Status: Completed
• Enrollment: 759
• Est. completion date: November 17, 2021
• Est. primary completion date: November 17, 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 (200 mg bid)
• Vancomycin
vancomycin (125 mg qid)

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires
Argentina	Hospital Ramos Mejía	Buenos Aires
Argentina	Instituto Medico Platense	Buenos Aires
Argentina	Hospital Privado Centro Medico Cordoba	Cordoba
Argentina	Centro Médico Talar	El Talar	Buenos Aires
Argentina	Instituto Medico ALAS	Salta
Australia	Sunshine Coast University Hospital	Birtinya	Queensland
Australia	Monash Medical Center	Clayton	Victoria
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Mater Misericordiae	South Brisbane	Queensland
Australia	Westmead Hospital	Westmead	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Brazil	Hospital Vera Cruz	Belo Horizonte	Minas Gerais
Brazil	Santa Casa De Misericordia De Belo Horizonte	Belo Horizonte	Minas Gerais
Brazil	Unidade de Pesquisa - NCS - Hospital Felício Rocho	Belo Horizonte	Minas Gerais
Brazil	Hospital das Clinicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Ernesto Dornelles	Porto Alegre	Rio Grande Do Sul
Brazil	Santa Casa de Misericordia de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto	Sao Jose do Rio Preto	Sao Paulo
Brazil	Hospital Alemao Oswaldo Cruz	Sao Paulo
Bulgaria	"MHAT - Blagoevgrad, EOOD Department of Gastroenterology"	Blagoevgrad
Bulgaria	MHAT "Sv.Ivan Rilski-2003"OOD	Dupnitsa	Kyustendil
Bulgaria	DCC1-Sliven Ltd.	Sliven
Bulgaria	DCC Alexandrovska	Sofia
Bulgaria	Medical center - Izgrev	Sofia
Canada	Foothills Medical Centre, South Tower	Calgary	Alberta
Canada	Moncton Hospital/Horizon Health Network	Moncton	New Brunswick
Canada	Centre Hospitalier de l'Universite de Montreal	Montréal	Quebec
Canada	Lakeridge Health	Oshawa	Ontario
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Québec- ULaval	Quebec
Canada	Recherche Médicale St-Jérôme Inc	Quebec
Canada	Centre integre universitaire de sante et de services sociaux de la Mauricie-et-du-Centre-du-Quebec	Trois-Rivières	Quebec
Greece	" ATTIKON University Hospital"	Athens
Greece	"'Hygeia'' Hospital 2nd Department of Medicine and Infectious Diseases"	Athens
Greece	"Pathophysiology Department Athens University Medical School"	Athens
Greece	General Hospital of Athens ''Alexandra''	Athens
Greece	General Hospital of Athens ''Evangelismos'	Athens
Greece	University Hospital of Heraklion	Heraklion
Greece	University Hospital of Patras	Patras
Greece	''Tzaneio'' General Hospital of Piraeus	Piraeus
Hungary	Dr. Kenessey Albert Kórház Rendelointézet, Tüdogyógyászati Aktív Osztály	Balassagyarmat
Hungary	Békés Megyei Központi Kórház Dr. Réthy Pál Tagkórház IV. Belgyógyászat - 2. Gasztroenterológia	Békéscsaba
Hungary	"Dél-Pesti Centrumkórház-OHII Szent László Kórház Infektológiai Osztály "	Budapest
Hungary	Országos Korányi Pulmonológiai Intézet, Központi Intenzív osztály	Budapest
Hungary	Békés Megyei Központi Kórház Pándy Kálmán Tagkórház, Infektológia-Hepatológia Osztály	Gyula	Békés
Hungary	Pest Megyei Flór Ferenc Kórház, V. Belgyógyászat	Kistarcsa	Pest Megye
Hungary	CRU Hungary Kft BAZ Megyei Kórház és Egyetemi Oktatókórház, Szent Ferenc Tagkórház	Miskolc
Hungary	"Pécsi Tudományegyetem I. sz. Belgyógyászat i Klinika, Infektológiai tanszék"	Pécs
Hungary	Pécsi Tudományegyetem Klinikai Központi Gyógyszertár	Pécs
Hungary	Csongrad County Dr. Bugyi Istvan Hospital, Dept. Of Internal Medicine	Szentes
Hungary	Javorszy Odon Hospital	Vác
Korea, Republic of	Hanyang University Seoul Hospital	Ansan	Seoul
Korea, Republic of	Korea University Ansan Hospital	Ansan-si	Gyeonggi-do
Korea, Republic of	Hallym University Kangnam Sacred Heart Hospital	Anyang-si	Seoul
Korea, Republic of	Hallym University Chuncheon Sacred Heart Hospital	Chuncheon	Gangwon-do
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu	Yeongnam
Korea, Republic of	Kyungpook National University Hospital	Daegu	Seoul
Korea, Republic of	Yeungnam University Medical Center	Daegu	Seoul
Korea, Republic of	Hanyang University Guri Hospital	Guri-Si	Gyeonggi-do
Korea, Republic of	Wonju Severance Christian Hospital	Ilsan-dong	Gangwondo
Korea, Republic of	Samsung Medical Center	Irwon-dong	Seoul
Korea, Republic of	Inje University Seoul Paik Hospital	Junggu
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Kangdong Sacred Heart Hospital	Seoul
Korea, Republic of	Asan Medical Center	Soeul
Korea, Republic of	Korea University Guro Hospital	Soeul
New Zealand	Waikato District Health Board Waikato Hospital	Hamilton	Waikato
New Zealand	Taranaki District Health Board TDHB - Taranaki Base Hospital	New Plymouth	Taranki
New Zealand	Waitemata District Health Board WDHB North Shore Hospital	Takapuna	Auckland
Poland	SP ZOZ w Bochni Szpital Powiatowy im. B. Marty Wieckiej	Bochnia
Poland	Szpital Bochenski SP ZOZ w Bochni	Bochnia
Poland	Klinika Chorób Zakaznych i Hepatologii Wojewódzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza	Bydgoszcz
Poland	Szpital Specjalistyczny w Chorzowie	Chorzów
Poland	Szpital Zakonu Bonifratrów	Katowice
Poland	Specjalistyczne Gabinety Sp z o.o.	Krakow
Poland	Korczowski Bartosz Gabinet	Rzeszow
Poland	Gabinet Lekarski Bartosz Korczowski	Rzeszów	Podkarpackie
Poland	ENDOSKOPIA Sp. z o.o.	Sopot
Poland	Centralny Szpital Kliniczny MSWiA Klinika Chorób Wewnetrznych i Gastroenterologii	Warszawa
Poland	Klinika Chorób Wewnetrznych i Gastroenterologii z Pododdzialem Leczenia Nieswoistych Chorób Zapalnych Jelit Centralny Szpital Kliniczny MSWiA	Warszawa
Poland	Wojewódzki Szpital Specjalistyczny im. J. Gromkowskiego we Wroclawiu; I Oddzial Chorób Zakaznych	Wroclaw
Romania	Clinical Hospital of Infectious and Tropical Diseases "Dr. Victor Babes"	Bucuresti
Romania	S.C. Sana Monitoring Srl	Bucuresti
Romania	Spitalul Clinic de Boli Infectioase si Tropicale	Bucuresti
Romania	SUUMC-Boli infectioase	Bucuresti
Romania	Spitalul Minicipal Caracal	Caracal
Romania	Spitalul Clinic de Boli Infectioase Constanta	Constanta
Romania	Spitalul Clinic de Boli Infectioase	Iasi
Romania	Spitalul Clinic de Boli Infectioase- Sfanta Parascheva	Iasi
Romania	Spitalul Clinic Judetean de Urgenta Timisoara	Timi?oara
Russian Federation	" State Budgetary Institution of Healthcare "City Clinical Hospital of n.a. V.M.Buyanova" "	Moscow
Russian Federation	State budget healthcare institution of Novosibirsk region "City clinical hospital #2"	Novosibirsk
Spain	Hospital Universitario Cruces	Barakaldo
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Reina Sofía. Hospital Provincial	Córdoba
Spain	"Hospital Universtiario Donostia "	Donostia
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	"Hospital Universitario Marqués de Valdecilla "	Santander
Spain	Hospital Universitario de Balme	Sevilla
Spain	Hospital Universitari Sant Joan de Reus	Tarragona
United States	GI Alliance - Texas Digestive Disease Consultants - Arlington	Arlington	Texas
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	University of Alabama - Birmingham	Birmingham	Alabama
United States	James J. Peters VAMC	Bronx	New York
United States	Mercury Street Medical Group PLLC	Butte	Montana
United States	GI Alliance - Texas Digestive Disease Consultants - Cedar Park	Cedar Park	Texas
United States	Chattanooga Research and Medicine CHARM	Chattanooga	Tennessee
United States	DM Clinical Research (Conroe Regional Hospital)	Conroe	Texas
United States	Infectious Disease Specialists of Atlanta	Decatur	Georgia
United States	Detroit Receiving Hospital Department of Pharmacy Services	Detroit	Michigan
United States	Harper Hospital Department of Pharmacy Services	Detroit	Michigan
United States	Aa Mrc Llc	Flint	Michigan
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	GI Alliance - Illinois Gastro Group - Glenview	Glenview	Illinois
United States	ECU Adult Specialty Care	Greenville	North Carolina
United States	Grand Teton Research Group PLLC	Idaho Falls	Idaho
United States	The University of Kansas Medical Center	Kansas City	Kansas
United States	FMC Science	Lampasas	Texas
United States	AB Clinical Trials	Las Vegas	Nevada
United States	Alliance Medical Research LLC	Lighthouse Point	Florida
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	Infectious Diseases Associates of Central VA	Lynchburg	Virginia
United States	Loyola University Medical Center	Maywood	Illinois
United States	Phoenix Medical Research LLC	Miami	Florida
United States	San Marcus Research	Miami Lakes	Florida
United States	Facey Medical Foundation	Mission Hills	California
United States	Gasteroenterology Group of Naples	Naples	Florida
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	New York Presbyterian Hospital Weill Cornell	New York	New York
United States	HeuerMD Research Inc	Orlando	Florida
United States	Pines Care Research Center Inc.	Pembroke Pines	Florida
United States	UnityPoint Health Peoria/Proctor	Peoria	Illinois
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Monument Health Clinical Research	Rapid City	South Dakota
United States	Paradigm Clinical Research Centers, Inc	Redding	California
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	University Of California Davis	Sacramento	California
United States	Professional Health Care of Pinellas	Saint Petersburg	Florida
United States	GI Alliance - Texas Digestive Disease Consultants - San Marcos	San Marcos	Texas
United States	Bardmoor Gastroenterology	Seminole	Florida
United States	Revival Research Institute, LLC.	Southfield	Michigan
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	GI Alliance - Arizona Digestive Health - Sun City	Sun City	Arizona
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Carle Foundation Hospital	Urbana	Illinois
United States	GI Alliance - Texas Digestive Disease Consultants - Webster	Webster	Texas
United States	PMG Research of Winston-Salem	Winston-Salem	North Carolina
United States	St. Vincent Hospital	Worcester	Massachusetts
United States	Florida Medical Clinic P.A.	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Summit Therapeutics

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Bulgaria,  Canada,  Greece,  Hungary,  Korea, Republic of,  New Zealand,  Poland,  Romania,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Sustained Clinical Response (SCR) Defined as Clinical Response and no Recurrence of CDI Through 30 Days Post End of Treatment (EOT).	This primary outcome measures the number of participants with Sustained Clinical Response (SCR). SCR is defined as Clinical Response and no recurrence of CDI through 30 days post End of Treatment (EOT). At D40, D70 and D100 the Investigator or medically qualified designee will determine if the patient has a sustained clinical response or experienced RECURRENCE since the previous assessment. The Investigator will assess cure/failure and recurrence based on available information which includes, but is not limited to, improvement from baseline in the number of UBMs, signs & symptoms of CDI, and the requirement for CDI medication. The Investigator should assess cure/failure in a way that best reflects the Investigator's standard clinical practice.	Day 40
Secondary	Clinical Response	defined as; less than 3 unformed bowel movements (UBMs) for 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	Relative Abundance of the 3 Main Bile Acid Groups (Conjugated Primary, Primary and Secondary Bile Acids) From Baseline to EOT.	This secondary outcome measures the relative abundance of the 3 main Bile Acid Groups (Conjugated Primary, Primary and Secondary Bile Acids) from Baseline to EOT.	Day 10
Secondary	Percentage of Change of a-diversity (Shannon Index) of the Microbiota in Stool Samples From Baseline to EOT.	This secondary outcome measures the percentage of change of a-diversity (Shannon Index) of the microbiota in stool samples from baseline to EOT. Shannon index is a weighted statistic measuring both species richness and evenness. The Shannon Index is calculated by taking the relative abundance of each species and sums the relative abundance times the natural log of the relative abundance for each species. The value is converted into a positive value by times minus one. A higher Shannon Index means higher diversity	Day 10
Secondary	Measure of ß-diversity of the Gut Microbiota Between Baseline and EOT Stool Samples (Bray-Curtis Index/Dissimilarity).	This secondary outcome measures the ß-diversity of the gut microbiota in stool samples from baseline to EOT. Bray-Curtis index/dissimilarity measures how different two samples are in the microbiome composition. The Bray-Curtis dissimilarity is graded between 0 and 1, where 0 means the two samples have the same composition (that is they share all the species and every species has the same abundance), and 1 means the two samples do not share any species.	Day 10

External Links

•   Metagenomic Analysis of the Differential Impact of Ridinilazole and Vancomycin on the Gut Microbiota in a Phase 2 Study