Clinical trial NCT06237452: VE303 for Prevention of Recurrent Clostridioides Difficile Infection
Official title: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of VE303 for Prevention of Recurrent Clostridioides Difficile Infection
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Clostridium Difficile
Clostridium Difficile Infections
Clostridium Difficile Infection Recurrence
Clostridioides Difficile Infection
Clostridioides Difficile Infection Recurrence
CDI
C. Diff Infection
Recurrent Clostridium Difficile Infection
C.Difficile Diarrhea
Diarrhea Infectious
Lead sponsor: Vedanta Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2024-02-01
Enrollment: 852
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The overall objective of the RESTORATiVE303 study is to evaluate the safety and the Clostridioides difficile infection (CDI) recurrence rate at Week 8 in participants who receive a 14-day course of VE303 or matching placebo. The objectives and endpoints are identical for Stage 1 (recurrent CDI) and Stage 2 (high-risk primary CDI).


Eligibility criteria: Key Inclusion Criteria (For enrollment in Stage 1: recurrent CDI population):

* Age ≥ 12 years where permitted, and ≥ 18 years in other locations, with a laboratory-confirmed qualifying episode of CDI and at least 1 prior occurrence within the last 6 months

Key Inclusion Criteria (For enrollment in Stage 2: primary CDI with high-risk for recurrence population):

* Age ≥ 75 years with a laboratory-confirmed qualifying episode of CDI
* OR age ≥ 12 years where permitted, and ≥ 18 years in other locations, with least two of the following risk factors:

  1. Age ≥ 65 years
  2. Kidney dysfunction, defined as estimated creatinine clearance \< 60 mL/min/1.73 m\^2 at the time of the qualifying CDI episode
  3. History of regular use of a proton pump inhibitor (PPI) within the past 2 months and expectation of continued use of PPIs throughout the study
  4. History of a prior CDI episode between 6 and 12 months prior to enrollment
  5. Immunosuppression due to an underlying disease or its treatment
  6. Has undergone solid organ or hematopoietic stem cell transplantation

Key Inclusion Criteria (For enrollment in Stage 1 or 2):

* The qualifying episode of CDI must meet all the following criteria:

  1. New onset of ≥ 3 unformed bowel movements (ie, Types 5 to 7 on the Bristol stool scale) within 24 hours for 2 consecutive days
  2. CDI symptoms started within 4 weeks prior to initiation of standard of care (SoC) antibiotic therapy for CDI
  3. Stool sample collected before (or no later than 72 hours after) initiation of SoC antibiotic therapy that was positive in a CDI laboratory test, defined as enzyme immunoassay (EIA) for toxin A/B and glutamate dehydrogenase (GDH) with polymerase chain reaction (PCR) reflex testing for discordant EIA/GDH results, performed at either a local laboratory or the central laboratory
  4. Diarrhea considered unlikely to have another etiology
* Prior to receiving any study medication, the participant should:

  1. Receive and complete a course of SoC antibiotic therapy for at least 10 days, up to a maximum of 28 days (Note: choice of agent is at the physician's discretion and antibiotic tapering is not allowed). It is permissible for decentralized participants to be randomized during SoC antibiotic administration.
  2. Meet the criterion of a successful clinical response, defined attaining symptomatic control of the qualifying CDI episode, ie, \< 3 loose/unformed bowel movements per 24 hours for at least 2 consecutive days
* Able to receive the first dose of study drug on the last planned day of SoC antibiotic administration for a qualifying CDI episode, or no later than 2 days after completion of antibiotic dosing
* Recovered from any complications of severe or fulminant CDI and be clinically stable by the time of randomization

Key Exclusion Criteria (For both Stage 1 and Stage 2):

* History of chronic diarrhea (defined as ≥ 3 loose stools per day lasting for at least 4 weeks) within 3 months prior to randomization that is not related to CDI
* Known or suspected toxic megacolon or small bowel ileus at the time of randomization
* History of confirmed celiac disease, inflammatory bowel disease, microscopic colitis, short gut, GI tract fistulas, or a recent episode (within 6 months of screening) of intestinal ischemia or ischemic colitis
* Receipt of bezlotoxumab during the course of SoC antibiotic treatment for the qualifying CDI episode
* Use of antidiarrheal drugs (eg, loperamide, diphenoxylate) within 3 days prior to the planned first dose of study drug
* Anticipated administration of oral or parenteral antibacterial therapy for a non-CDI indication after randomization through Week 24 (end of study)
* Probiotics, whether characterized as a dietary/food supplement, or a drug, are prohibited within 2 days before starting study drug and through the dosing period. (Note: consumption of food-based products such as yogurt, kombucha, and kefir are permitted.)
* Absolute neutrophil count (ANC) of \< 0.5 ×10\^9 cells/L on 2 consecutive occasions within 7 days prior to randomization, or sustained ANC \< 1.0 × 10\^9 cells/L

Primary outcomes:
measure: CDI Recurrence Rate at Week 8
timeFrame: 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Advanced Gastroenterology, P.C.
state: Arizona
city: Apple Valley
country: United States
facility: Om Research, LLC
state: California
city: Culver City
country: United States
facility: Science 37 Inc (Remote/Home option)
state: California
city: San Diego
country: United States
facility: VA San Diego Healthcare System
state: California
city: San Dimas
country: United States
facility: North America Research Institute
state: California
city: Thousand Oaks
country: United States
facility: Clinical Trials Management Services
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
state: California
city: Hamden
country: United States
facility: Medical Research Center of Connecticut
state: Connecticut
city: Clearwater
country: United States
facility: Gastro Florida
state: Florida
city: Fort Lauderdale
country: United States
facility: Proactive Clinical Research, LLC
state: Florida
city: Jacksonville
country: United States
facility: Encore Borland-Groover Clinical Research
state: Florida
city: Naples
country: United States
facility: GI Pros Research
state: Florida
city: Port Orange
country: United States
facility: Advanced Medical Research Center
state: Florida
city: Saint Cloud
country: United States
facility: KM International Research Operation LLC
state: Florida
city: Tampa
country: United States
facility: James A. Haley Veterans' Hospital
state: Florida
city: Tampa
country: United States
facility: International Center for Research
state: Florida
city: Athens
country: United States
facility: Summit Clinical Research, LLC
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Decatur
country: United States
facility: Metro Infectious Disease Consultants
state: Georgia
city: LaGrange
country: United States
facility: Regional Infectious Diseases and Infusion Center, Inc.
state: Georgia
city: Marietta
country: United States
facility: Gastrointestinal Specialists of Georgia
state: Georgia
city: Idaho Falls
country: United States
facility: Snake River Research, PLLC
state: Idaho
city: Burr Ridge
country: United States
facility: Metro Infectious Disease Consultants
state: Illinois
city: Evanston
country: United States
facility: NorthShore University Health System - Evanston Hospital
state: Illinois
city: Island Lake
country: United States
facility: Innovative Clinical Research Center, LLC (ICRC)
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health University Hospital
state: Indiana
city: Newburgh
country: United States
facility: Deaconess GI Specialty Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: IDC Clinical Research, LLC
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Chevy Chase
country: United States
facility: MGG Group Co., Inc., Chevy Chase Clinical Research
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: LTC Charles S. Kettles VA Medical Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health
state: Michigan
city: Royal Oak
country: United States
facility: Corewell Health William Beaumont University Hospital
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Plymouth
country: United States
facility: MNGI Digestive Health, PA
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Southaven
country: United States
facility: Delta Gastroenterology and Endoscopy Center
state: Mississippi
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Weldon Spring
country: United States
facility: St. Charles Clinical Research
state: Missouri
city: New Brunswick
country: United States
facility: Rutgers Robert Wood Johnson Medical School
state: New Jersey
city: Somers Point
country: United States
facility: South Jersey Infectious Disease
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Manhasset
country: United States
facility: Northwell Health Division of Infectious Diseases
state: New York
city: New York
country: United States
facility: NYU Grossman School of Medicine
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Manhattan Clinical Research, LLC
state: New York
city: Syracuse
country: United States
facility: Syracuse VA Medical Center
state: New York
city: Toledo
country: United States
facility: Toledo Institute of Clinical Research
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma City Veterans Affairs Healthcare System
state: Oklahoma
city: Harrisburg
country: United States
facility: Susquehanna Research Group - Gastroenterology
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Medical Group, PC
state: Pennsylvania
city: Uniontown
country: United States
facility: Frontier Clinical Research
state: Pennsylvania
city: Charleston
country: United States
facility: Ralph H. Johnson VA Health Care System
state: South Carolina
city: Charleston
country: United States
facility: Ralph H. Johnson VA Health Care System
state: South Carolina
city: Charleston
country: United States
facility: Lowcountry Infectious Diseases, P.A.
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: North Texas Infectious Disease Consultants, P.A.
state: Texas
city: Houston
country: United States
facility: University of Houston College of Pharmacy
state: Texas
city: Katy
country: United States
facility: BioStar Clinical Research
state: Texas
city: Sugar Land
country: United States
facility: Simcare Medical Research, LLC
state: Texas
city: Seattle
country: United States
facility: Seattle Infectious Disease Clinic
state: Washington
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Parkville
country: Australia
facility: Melbourne Health
state: Victoria
city: Anderlecht
country: Belgium
facility: Erasme University Hospital - Infectiology Department
city: Brussels
country: Belgium
facility: Universite Catholique De Louvain and Cliniques Universitaires Saint-Luc
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Sofia
country: Bulgaria
facility: Medical Center Excelsior OOD, Base 1
state: Sofia-Grad
city: Burgas
country: Bulgaria
facility: UMHAT Burgas AD
city: Gorna Oryahovitsa
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment St. Ivan Rilski Gorna Oriahovitsa EOOD
city: Lom
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Sveti Nikolay Chuditvorets EOOD
city: Plovdiv
country: Bulgaria
facility: Medicinski centar Hipokrat-N EOOD
city: Sliven
country: Bulgaria
facility: MHAT Dr.Ivan Seliminski - Sliven Ltd.
city: Calgary
country: Canada
facility: Alberta Health Services (AHS) - Foothills Medical Centre
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Red Deer
country: Canada
facility: CaRe Clinic
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver Coastal Health Research Institute - Immunity and Infection Research Centre
state: British Columbia
city: Moncton
country: Canada
facility: The Moncton Hospital
state: New Brunswick
city: St. John's
country: Canada
facility: NL Health Services
state: Newfoundland and Labrador
city: Hamilton
country: Canada
facility: Research St. Josephs Hamilton
state: Ontario
city: London
country: Canada
facility: St. Joseph's Hospital - London
state: Ontario
city: Scarborough
country: Canada
facility: Viable Clinical Research Corporation
state: Ontario
city: Chicoutimi
country: Canada
facility: INTERMED groupe santé
state: Quebec
city: Quebec
country: Canada
facility: Centre Hospitalier de l Universite Laval (CHUL)
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
state: Brno-město
city: Kyjov
country: Czechia
facility: Nemocnice Kyjov, p.o.
city: Ostrava-Poruba
country: Czechia
facility: Fakultni Nemocnice Ostrava
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
state: Central Jutland
city: Dijon
country: France
facility: Hôpital du Bocage
state: Franche-Comté
city: Nantes
country: France
facility: CHU de Nantes - Hôtel Dieu
state: Loire-Atlantique
city: Lyon
country: France
facility: Hôpital De La Croix Rousse - Gastroenterology
state: Rhone
city: Tours Cedex 9
country: France
facility: Chru De Tours
city: Tbilisi
country: Georgia
facility: ISR-GEO Med Res Clin Healthycore
city: Tbilisi
country: Georgia
facility: LTD "Emergency Cardiology Center named by Acad.G.Chapidze"
city: Tbilisi
country: Georgia
facility: LTD "Academician Vakhtang Bochorishvili Clinic"
city: Tbilisi
country: Georgia
facility: LTD "Aversi Clinic"
city: Berlin
country: Germany
facility: Epimed GmbH
city: Békéscsaba
country: Hungary
facility: Bekes Varmegyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaza
state: Békés
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont, I. sz. Belgyogyaszati Klinika
state: Csongrád
city: Tatabanya
country: Hungary
facility: Komárom-Esztergom Vármegyei Szent Borbála Kórház
state: Komárom-Esztergom
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Nyíregyháza
country: Hungary
facility: Szabolcs-Szatmár-Bereg Vármegyei Oktatókórház Nyíregyházi Jósa András Tagkórház
city: Drogheda
country: Ireland
facility: Our Lady of Lourdes Hospital
state: Louth
city: Ashkelon
country: Israel
facility: The Barzilai Medical Center
state: HaDarom
city: Petah Tikva
country: Israel
facility: Rabin Medical Center - Beilinson Hospital
state: HaMerkaz
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
state: HaMerkaz
city: Zerifin
country: Israel
facility: Shamir Medical Center (Assaf Harofeh)
state: HaMerkaz
city: Jerusalem
country: Israel
facility: Hadassah Medical Centre
state: Yerushalayim
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Tel Hashomer
country: Israel
facility: The Chaim Sheba Medical Center
city: Lecco
country: Italy
facility: PO A. Manzoni di Lecco, ASST Lecco
state: Lombardia
city: Monza
country: Italy
facility: ASST Monza
state: Monza e Brianza
city: Vittorio Veneto
country: Italy
facility: Presidio Ospedaliero di Vittorio Veneto
state: Veneto
city: Alessandria
country: Italy
facility: AO Nazionale SS. Antonio e Biagio e C. Arrigo
city: Milano
country: Italy
facility: Ospedale Fatebenefratelli e Oftalmico, ASST Fatebenefratelli Sacco
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo, Università degli studi di Pavia
city: Pisa
country: Italy
facility: AOU Pisana - Stabilimento di Cisanello
city: Roma
country: Italy
facility: Osp. Pediatrico Bambino Gesù, IRCCS
city: Roma
country: Italy
facility: Ospedale Isola Tiberina Gemelli Isola
city: Aguascalientes
country: Mexico
facility: Centro de Investigacion Medica Aguascalientes
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum (LUMC)
state: Zuid-Holland
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum (UMC) Utrecht - Julius Center for Health Sciences and Primary Care
city: Warszawa
country: Poland
facility: NZOZ VIVAMED Jadwiga Miecz
state: Mazowieckie
city: Katowice
country: Poland
facility: Gyncentrum sp. z o.o.
state: Slaskie
city: Guimaraes
country: Portugal
facility: Unidade Local De Saude Do Alto Ave E.P.E.
state: Braga
city: Almada
country: Portugal
facility: Unidade Local De Saude De Almada-Seixal E.P.E.
state: Lisboa
city: Braga
country: Portugal
facility: CCAB Centro Clinico Academico Braga Associacao - ULS Braga
city: Coimbra
country: Portugal
facility: Unidade Local De Saude De Coimbra E.P.E.
city: Guarda
country: Portugal
facility: Unidade Local de Saúde da Guarda (ULSG)
city: Porto
country: Portugal
facility: Unidade Local De Saude De Santo Antonio E.P.E.
city: Vila Nova de Gaia
country: Portugal
facility: Unidade Local De Saude De Gaia/Espinho E.P.E.
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic de Boli Infectioase Cluj-Napoca
state: Cluj
city: Craiova
country: Romania
facility: Centrul Medical Renasterea
state: Dolj
city: Timisoara
country: Romania
facility: Spitalul Clinic Judetean De Urgenta Pius Brinzeu Timisoara
state: Timis
city: Bucuresti
country: Romania
facility: Institutul de Boli Infecțioase Prof Dr Matei Bals - Infectious diseases V
city: Bucuresti
country: Romania
facility: Spitalul Clinic de Boli Infectioase si Tropicale Dr Victor Babes
city: Iasi
country: Romania
facility: Spitalul Clinic de Boli Infectioase Sfanta Parascheva Iasi - Infectious diseases I
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Universitario Mutua de Terrassa
state: Barcelona
city: San Sebastián
country: Spain
facility: H. U. Donostia
state: Guipúzcoa
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta De Hierro Majadahonda
state: Madrid
city: A Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña
city: Alicante
country: Spain
facility: Hospital General Universitario Dr Balmis
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Gregorio Marañón University Hospital
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz - UCICEC
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen De La Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Bournemouth
country: United Kingdom
facility: The Royal Bournemouth Hospital
city: Bristol
country: United Kingdom
facility: North Bristol NHS Trust - Southmead Hospital, Clinical Research Centre
city: Edinburgh
country: United Kingdom
facility: NHS Lothian - Western General Hospital
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: St.Thomas' Hospital
city: Sheffield
country: United Kingdom
facility: Northern General Hospital
city: Swansea
country: United Kingdom
facility: Morriston Hospital
Study officials:
References: