Clinical trial NCT03595553: Comparison of 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Clostridioides Difficile Infection
Keywords: Clostridioides difficile
Clostridium difficile
C. difficile
C. diff
Lead sponsor: Summit Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-07-23
Enrollment: 759
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


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.

Primary outcomes:
measure: 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).
timeFrame: Day 40
Secondary outcomes:
measure: Clinical Response
timeFrame: Day 12
measure: Clinical Cure
timeFrame: Day 12
measure: Sustained Clinical Response Over 60 Days
timeFrame: Day 70
measure: Sustained Clinical Response Over 90 Days
timeFrame: Day 100
measure: Relative Abundance of the 3 Main Bile Acid Groups (Conjugated Primary, Primary and Secondary Bile Acids) From Baseline to EOT.
timeFrame: Day 10
measure: Percentage of Change of α-diversity (Shannon Index) of the Microbiota in Stool Samples From Baseline to EOT.
timeFrame: Day 10
measure: Measure of β-diversity of the Gut Microbiota Between Baseline and EOT Stool Samples (Bray-Curtis Index/Dissimilarity).
timeFrame: Day 10
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Birmingham
state: Alabama
city: Sun City
country: United States
facility: GI Alliance - Arizona Digestive Health - Sun City
state: Arizona
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Mission Hills
country: United States
facility: Facey Medical Foundation
state: California
city: Redding
country: United States
facility: Paradigm Clinical Research Centers, Inc
state: California
city: Sacramento
country: United States
facility: University Of California Davis
state: California
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Lighthouse Point
country: United States
facility: Alliance Medical Research LLC
state: Florida
city: Miami Lakes
country: United States
facility: San Marcus Research
state: Florida
city: Miami
country: United States
facility: Phoenix Medical Research LLC
state: Florida
city: Naples
country: United States
facility: Gasteroenterology Group of Naples
state: Florida
city: Orlando
country: United States
facility: HeuerMD Research Inc
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Care Research Center Inc.
state: Florida
city: Saint Petersburg
country: United States
facility: Professional Health Care of Pinellas
state: Florida
city: Seminole
country: United States
facility: Bardmoor Gastroenterology
state: Florida
city: Zephyrhills
country: United States
facility: Florida Medical Clinic P.A.
state: Florida
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta
state: Georgia
city: Idaho Falls
country: United States
facility: Grand Teton Research Group PLLC
state: Idaho
city: Glenview
country: United States
facility: GI Alliance - Illinois Gastro Group - Glenview
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Peoria
country: United States
facility: UnityPoint Health Peoria/Proctor
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Urbana
country: United States
facility: Carle Foundation Hospital
state: Illinois
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Worcester
country: United States
facility: St. Vincent Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Harper Hospital Department of Pharmacy Services
state: Michigan
city: Detroit
country: United States
facility: Detroit Receiving Hospital Department of Pharmacy Services
state: Michigan
city: Flint
country: United States
facility: Aa Mrc Llc
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Southfield
country: United States
facility: Revival Research Institute, LLC.
state: Michigan
city: Butte
country: United States
facility: Mercury Street Medical Group PLLC
state: Montana
city: Las Vegas
country: United States
facility: AB Clinical Trials
state: Nevada
city: Bronx
country: United States
facility: James J. Peters VAMC
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital Weill Cornell
state: New York
city: Greenville
country: United States
facility: ECU Adult Specialty Care
state: North Carolina
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem
state: North Carolina
city: Toledo
country: United States
facility: St. Vincent Mercy Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Rapid City
country: United States
facility: Monument Health Clinical Research
state: South Dakota
city: Chattanooga
country: United States
facility: Chattanooga Research and Medicine CHARM
state: Tennessee
city: Arlington
country: United States
facility: GI Alliance - Texas Digestive Disease Consultants - Arlington
state: Texas
city: Cedar Park
country: United States
facility: GI Alliance - Texas Digestive Disease Consultants - Cedar Park
state: Texas
city: Conroe
country: United States
facility: DM Clinical Research (Conroe Regional Hospital)
state: Texas
city: Lampasas
country: United States
facility: FMC Science
state: Texas
city: San Marcos
country: United States
facility: GI Alliance - Texas Digestive Disease Consultants - San Marcos
state: Texas
city: Webster
country: United States
facility: GI Alliance - Texas Digestive Disease Consultants - Webster
state: Texas
city: Lynchburg
country: United States
facility: Infectious Diseases Associates of Central VA
state: Virginia
city: El Talar
country: Argentina
facility: Centro Médico Talar
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Instituto Medico Platense
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Buenos Aires
country: Argentina
facility: Hospital Ramos Mejía
city: Cordoba
country: Argentina
facility: Hospital Privado Centro Medico Cordoba
city: Salta
country: Argentina
facility: Instituto Medico ALAS
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Misericordiae
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Medical Center
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Belo Horizonte
country: Brazil
facility: Unidade de Pesquisa - NCS - Hospital Felício Rocho
state: Minas Gerais
city: Belo Horizonte
country: Brazil
facility: Hospital Vera Cruz
state: Minas Gerais
city: Belo Horizonte
country: Brazil
facility: Santa Casa De Misericordia De Belo Horizonte
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericordia de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Ernesto Dornelles
state: Rio Grande Do Sul
city: Sao Jose do Rio Preto
country: Brazil
facility: Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
city: Dupnitsa
country: Bulgaria
facility: MHAT "Sv.Ivan Rilski-2003"OOD
state: Kyustendil
city: Blagoevgrad
country: Bulgaria
facility: "MHAT - Blagoevgrad, EOOD Department of Gastroenterology"
city: Sliven
country: Bulgaria
facility: DCC1-Sliven Ltd.
city: Sofia
country: Bulgaria
facility: DCC Alexandrovska
city: Sofia
country: Bulgaria
facility: Medical center - Izgrev
city: Calgary
country: Canada
facility: Foothills Medical Centre, South Tower
state: Alberta
city: Moncton
country: Canada
facility: Moncton Hospital/Horizon Health Network
state: New Brunswick
city: Oshawa
country: Canada
facility: Lakeridge Health
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Trois-Rivières
country: Canada
facility: Centre integre universitaire de sante et de services sociaux de la Mauricie-et-du-Centre-du-Quebec
state: Quebec
city: Quebec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Québec- ULaval
city: Quebec
country: Canada
facility: Recherche Médicale St-Jérôme Inc
city: Athens
country: Greece
facility: General Hospital of Athens ''Evangelismos'
city: Athens
country: Greece
facility: General Hospital of Athens ''Alexandra''
city: Athens
country: Greece
facility: "Pathophysiology Department Athens University Medical School"
city: Athens
country: Greece
facility: " ATTIKON University Hospital"
city: Athens
country: Greece
facility: "'Hygeia'' Hospital 2nd Department of Medicine and Infectious Diseases"
city: Heraklion
country: Greece
facility: University Hospital of Heraklion
city: Patras
country: Greece
facility: University Hospital of Patras
city: Piraeus
country: Greece
facility: ''Tzaneio'' General Hospital of Piraeus
city: Gyula
country: Hungary
facility: Békés Megyei Központi Kórház Pándy Kálmán Tagkórház, Infektológia-Hepatológia Osztály
state: Békés
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flór Ferenc Kórház, V. Belgyógyászat
state: Pest Megye
city: Balassagyarmat
country: Hungary
facility: Dr. Kenessey Albert Kórház Rendelőintézet, Tüdőgyógyászati Aktív Osztály
city: Budapest
country: Hungary
facility: "Dél-Pesti Centrumkórház-OHII Szent László Kórház Infektológiai Osztály "
city: Budapest
country: Hungary
facility: Országos Korányi Pulmonológiai Intézet, Központi Intenzív osztály
city: Békéscsaba
country: Hungary
facility: Békés Megyei Központi Kórház Dr. Réthy Pál Tagkórház IV. Belgyógyászat - 2. Gasztroenterológia
city: Miskolc
country: Hungary
facility: CRU Hungary Kft BAZ Megyei Kórház és Egyetemi Oktatókórház, Szent Ferenc Tagkórház
city: Pécs
country: Hungary
facility: "Pécsi Tudományegyetem I. sz. Belgyógyászat i Klinika, Infektológiai tanszék"
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem Klinikai Központi Gyógyszertár
city: Szentes
country: Hungary
facility: Csongrad County Dr. Bugyi Istvan Hospital, Dept. Of Internal Medicine
city: Vác
country: Hungary
facility: Javorszy Odon Hospital
city: Chuncheon
country: Korea, Republic of
facility: Hallym University Chuncheon Sacred Heart Hospital
state: Gangwon-do
city: Ilsan-dong
country: Korea, Republic of
facility: Wonju Severance Christian Hospital
state: Gangwondo
city: Ansan-si
country: Korea, Republic of
facility: Korea University Ansan Hospital
state: Gyeonggi-do
city: Guri-Si
country: Korea, Republic of
facility: Hanyang University Guri Hospital
state: Gyeonggi-do
city: Ansan
country: Korea, Republic of
facility: Hanyang University Seoul Hospital
state: Seoul
city: Anyang-si
country: Korea, Republic of
facility: Hallym University Kangnam Sacred Heart Hospital
state: Seoul
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
state: Seoul
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Medical Center
state: Seoul
city: Irwon-dong
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
state: Yeongnam
city: Junggu
country: Korea, Republic of
facility: Inje University Seoul Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: Kangdong Sacred Heart Hospital
city: Soeul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Soeul
country: Korea, Republic of
facility: Asan Medical Center
city: Takapuna
country: New Zealand
facility: Waitemata District Health Board WDHB North Shore Hospital
state: Auckland
city: New Plymouth
country: New Zealand
facility: Taranaki District Health Board TDHB - Taranaki Base Hospital
state: Taranki
city: Hamilton
country: New Zealand
facility: Waikato District Health Board Waikato Hospital
state: Waikato
city: Rzeszów
country: Poland
facility: Gabinet Lekarski Bartosz Korczowski
state: Podkarpackie
city: Bochnia
country: Poland
facility: SP ZOZ w Bochni Szpital Powiatowy im. B. Marty Wieckiej
city: Bochnia
country: Poland
facility: Szpital Bocheński SP ZOZ w Bochni
city: Bydgoszcz
country: Poland
facility: Klinika Chorób Zakaźnych i Hepatologii Wojewódzki Szpital Obserwacyjno-Zakaźny im. Tadeusza Browicza
city: Chorzów
country: Poland
facility: Szpital Specjalistyczny w Chorzowie
city: Katowice
country: Poland
facility: Szpital Zakonu Bonifratrów
city: Krakow
country: Poland
facility: Specjalistyczne Gabinety Sp z o.o.
city: Rzeszow
country: Poland
facility: Korczowski Bartosz Gabinet
city: Sopot
country: Poland
facility: ENDOSKOPIA Sp. z o.o.
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSWiA Klinika Chorób Wewnętrznych i Gastroenterologii
city: Warszawa
country: Poland
facility: Klinika Chorób Wewnętrznych i Gastroenterologii z Pododdziałem Leczenia Nieswoistych Chorób Zapalnych Jelit Centralny Szpital Kliniczny MSWiA
city: Wroclaw
country: Poland
facility: Wojewódzki Szpital Specjalistyczny im. J. Gromkowskiego we Wrocławiu; I Oddział Chorób Zakaźnych
city: Bucuresti
country: Romania
facility: SUUMC-Boli infectioase
city: Bucuresti
country: Romania
facility: Clinical Hospital of Infectious and Tropical Diseases "Dr. Victor Babes"
city: Bucuresti
country: Romania
facility: S.C. Sana Monitoring Srl
city: Bucuresti
country: Romania
facility: Spitalul Clinic de Boli Infectioase si Tropicale
city: Caracal
country: Romania
facility: Spitalul Minicipal Caracal
city: Constanta
country: Romania
facility: Spitalul Clinic de Boli Infectioase Constanta
city: Iasi
country: Romania
facility: Spitalul Clinic de Boli Infectioase- Sfanta Parascheva
city: Iaşi
country: Romania
facility: Spitalul Clinic de Boli Infectioase
city: Timișoara
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Timisoara
city: Moscow
country: Russian Federation
facility: " State Budgetary Institution of Healthcare "City Clinical Hospital of n.a. V.M.Buyanova" "
city: Novosibirsk
country: Russian Federation
facility: State budget healthcare institution of Novosibirsk region "City clinical hospital #2"
city: Barakaldo
country: Spain
facility: Hospital Universitario Cruces
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía. Hospital Provincial
city: Donostia
country: Spain
facility: "Hospital Universtiario Donostia "
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Santander
country: Spain
facility: "Hospital Universitario Marqués de Valdecilla "
city: Sevilla
country: Spain
facility: Hospital Universitario de Balme
city: Tarragona
country: Spain
facility: Hospital Universitari Sant Joan de Reus
Study officials:
affiliation: Summit Therapeutics
name: Lori Styles, MD
role: STUDY_DIRECTOR
References:
citation: 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.