VE303 for Prevention of Recurrent Clostridioides Difficile Infection

Purpose

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).

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

Eligibility

Eligible Ages
Over 12 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Prevention
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
VE303
Subjects assigned to the VE303 arm will take 3 capsules containing VE303 per day for 14 days after completing 10 to 21 days of standard of care antibiotic treatment for the qualifying CDI episode.
  • Biological: VE303
    VE303 is a live biotherapeutic product (LBP) consisting of 8 clonally derived, nonpathogenic, nontoxigenic, commensal bacteria strains manufactured under Good Manufacturing Practices (GMP) conditions.
Placebo Comparator
Placebo
Subjects assigned to the placebo arm will take 3 placebo capsules per day for 14 days after completing 10 to 21 days of standard of care antibiotic treatment for the qualifying CDI episode.
  • Biological: Placebo
    Placebo capsules contain microcrystalline cellulose. Placebo capsules are visually identical to and not discernible from VE303 capsules. Placebo capsules will not contain any VE303 drug product.

Recruiting Locations

Om Research, LLC
Apple Valley 5324363, California 5332921 92307
Contact:
Tara Mckenzie
661-388-2239
tmckenzie@omclinicaltrials.com

Science 37 Inc (Remote/Home option)
Culver City 5341114, California 5332921 90230
Contact:
Debra Weinstein, MD
323-815-7793
restorative303@science37.com

Children's Hospital of Philadelphia
Los Angeles 5368361, California 5332921 90027
Contact:
Victor Yu
323-361-8481
vyu@chla.usc.edu

VA San Diego Healthcare System
San Diego 5391811, California 5332921 92161
Contact:
David Looney, MD
(858) 552-8585
David.Looney@va.gov

North America Research Institute
San Dimas 5391891, California 5332921 91773
Contact:
Yesenia Olivas
1-800-797-1695
yguzman@nariresearch.com

Clinical Trials Management Services
Thousand Oaks 5402405, California 5332921 91360
Contact:
Teresa Tocher
805-906-7800
siteservices@clinicaltrialsmanagementservices.com

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance 5403022, California 5332921 90502
Contact:
Janine La Page
310-222-4104
jlapage@lundquist.org

Medical Research Center of Connecticut
Hamden 4835654, Connecticut 4831725 06518
Contact:
Candace Cotto
904-680-0871
ccotto@gastrocenter.org

Gastro Florida
Clearwater 4151316, Florida 4155751 33756
Contact:
Tara Wasson-Olden
727-347-0005
tolden@gastrofl.com

Proactive Clinical Research, LLC
Fort Lauderdale 4155966, Florida 4155751 33308
Contact:
Carolyn Zambrano
954-938-2843
czambrano@proactivecr.com

Encore Borland-Groover Clinical Research
Jacksonville 4160021, Florida 4155751 32256
Contact:
Cynthia Buda
904-621-0390
cbuda@encoredocs.com

GI Pros Research
Naples 4165565, Florida 4155751 34102
Contact:
Paula Allain
239-649-1336
pallainresearch@gmail.com

Advanced Medical Research Center
Port Orange 4169156, Florida 4155751 32127
Contact:
Mohamed Alharami
386-767-8800
mhekmat@amrcus.com

KM International Research Operation LLC
Saint Cloud 4170965, Florida 4155751 34769
Contact:
Kadidia Kone-Merchant
321-805-4774
kad@kminternationalresearchoperationllc.com

James A. Haley Veterans' Hospital
Tampa 4174757, Florida 4155751 33612
Contact:
John F Toney, MD
813-972-2000
john.toney@va.gov

International Center for Research
Tampa 4174757, Florida 4155751 33614
Contact:
Laura Porro
786-308-1157
Lporro@ICR-Health.org

Summit Clinical Research, LLC
Athens 4180386, Georgia 4197000 30607
Contact:
Jeffrey Williams, MD
jwilliams@summitclinicalstudies.com

Emory University Hospital Midtown
Atlanta 4180439, Georgia 4197000 30308
Contact:
Nirja Mehta, MD
470-839-5804
nirja.mehta@emory.edu

Metro Infectious Disease Consultants
Decatur 4191124, Georgia 4197000 30033
Contact:
Jaol Matos
jmatos@idsatlanta.com

Regional Infectious Diseases and Infusion Center, Inc.
La Grange 4204230, Georgia 4197000 30240
Contact:
Bhuvan Doneepudi
706-739-7789
bhuvan@nobadbugs.com

Gastrointestinal Specialists of Georgia
Marietta 4207783, Georgia 4197000 30060
Contact:
Octavia Nichols
678-819-4237
onichols@gigeorgia.com

Snake River Research, PLLC
Idaho Falls 5596475, Idaho 5596512 83404
Contact:
Jennifer Morrison
208-535-8406
jmorrison@snakerr.com

Metro Infectious Disease Consultants
Burr Ridge 4886090, Illinois 4896861 60527
Contact:
Sarah Arnold
630-655-8441
sarnold@innovativeventures.com

NorthShore University Health System - Evanston Hospital
Evanston 4891382, Illinois 4896861 60201
Contact:
Kirsten Anderson
224-364-7971
KAnderson5@northshore.org

Innovative Clinical Research Center, LLC (ICRC)
Island Lake 4897579, Illinois 4896861 60042
Contact:
Bibi Ugbi-Okonkwo
bibi@icrcllc.com

Indiana University Health University Hospital
Indianapolis 4259418, Indiana 4921868 46202
Contact:
Renee Hewitt
317-278-9294
iuibd@iupui.edu

Deaconess GI Specialty Center
Newburgh 4262171, Indiana 4921868 47630
Contact:
Madeline Bryant
812-474-7184
research@deaconess.com

University of Kansas Medical Center
Kansas City 4273837, Kansas 4273857 66160
Contact:
Melissa Willer
913-945-6770
mwiller@kumc.edu

Ochsner Clinic Foundation
New Orleans 4335045, Louisiana 4331987 70121
Contact:
Julie Castex
504-842-7154
jcastex@ochsner.org

Johns Hopkins Hospital
Baltimore 4347778, Maryland 4361885 21287
Contact:
Zoey Onambele
410-955-6337
zonambe1@jhu.edu

MGG Group Co., Inc., Chevy Chase Clinical Research
Chevy Chase 4351335, Maryland 4361885 20815
Contact:
Gilbert Horst
301-652-5520
ghorst@jointopo.com

Tufts Medical Center
Boston 4930956, Massachusetts 6254926 02111
Contact:
Dulia Santos
617-636-4714
Dulia.santos@tuftsmedicine.org

Massachusetts General Hospital
Boston 4930956, Massachusetts 6254926 02114
Contact:
Elizabeth Hohmann, MD
617-724-7432
ehohmann@mgh.harvard.edu

Brigham and Women's Hospital
Boston 4930956, Massachusetts 6254926 02115
Contact:
Grace Hardwick
617-525-7011
ghardwick@bwh.harvard.edu

LTC Charles S. Kettles VA Medical Center
Ann Arbor 4984247, Michigan 5001836 48105
Contact:
Kimberly Nofz
734-845-5522
kimberly.nofz@va.gov

Henry Ford Health
Detroit 4990729, Michigan 5001836 48202
Contact:
Anita Shallal, MD
313-850-7032
ashalla2@hfhs.org

Corewell Health William Beaumont University Hospital
Royal Oak 5007804, Michigan 5001836 48073
Contact:
Maureen Cooney
248-551-2544
Maureen.Cooney@corewellhealth.org

University of Minnesota Medical Center
Minneapolis 5037649, Minnesota 5037779 55455
Contact:
Makenzie Richard
612-625-8090
rich1400@umn.edu

Mayo Clinic
Rochester 5043473, Minnesota 5037779 55905
Contact:
Patricia Kramer
507-538-1827
kammer.patricia@mayo.edu

University of Missouri
Columbia 4381982, Missouri 4398678 65212
Contact:
Syed Naqvi, MD
573-884-9075
naqvis@halth.missouri.edu

Washington University School of Medicine
St Louis 4407066, Missouri 4398678 63110
Contact:
Teresa Arb
314-747-1217
arbt@wustl.edu

St. Charles Clinical Research
Weldon Spring 4413926, Missouri 4398678 63304

Rutgers Robert Wood Johnson Medical School
New Brunswick 5101717, New Jersey 5101760 08901
Contact:
Therese Pagulayan
732-235-6128
tup1@rwjms.rutgers.edu

South Jersey Infectious Disease
Somers Point 4504186, New Jersey 5101760 08244
Contact:
Kelly Freeman
609-927-6662
kelly.freeman@sjidtrials.net

Northwell Health Division of Infectious Diseases
Manhasset 5125766, New York 5128638 11030
Contact:
Jessica Rao
516-562-3363
JCabildo@Northwell.edu

NYU Grossman School of Medicine
New York 5128581, New York 5128638 10016
Contact:
Nathasha Melukkaran
646-754-3417
Nathasha.melukkaran@nyulangone.org

New York Presbyterian Hospital
New York 5128581, New York 5128638 10021
Contact:
Tiffany Min
646-962-4463
tim9064@med.cornell.edu

Manhattan Clinical Research, LLC
New York 5128581, New York 5128638 10279
Contact:
Glenda Alfonso-Castillo
718-737-3786
galfonso.mcr@gmail.com

Toledo Institute of Clinical Research
Toledo 5174035, Ohio 5165418 43617
Contact:
Faheem Husain
419-819-9969
Faheem.Husain@ohmiallergy.com

Oklahoma City Veterans Affairs Healthcare System
Oklahoma City 4544349, Oklahoma 4544379 73104
Contact:
Stephen Farriester
405-456-3107
Stephen.Farriester@va.gov

Susquehanna Research Group - Gastroenterology
Harrisburg 5192726, Pennsylvania 6254927 17110
Contact:
Jessica Balay
717-914-7770
jbalay@gicare.com

Children's Hospital of Philadelphia
Philadelphia 4560349, Pennsylvania 6254927 19104
Contact:
Kelly Menna
215-590-3669
mennak@chop.edu

Guthrie Medical Group, PC
Sayre 5211037, Pennsylvania 6254927 18840
Contact:
Ukorn Srivatana, MD
1-800-836-0388
Clinical.research@guthrie.org

Frontier Clinical Research
Uniontown 4561859, Pennsylvania 6254927 15401
Contact:
Kim Chapman
724-596-8036
kchapman@frontierclinical.com

Ralph H. Johnson VA Health Care System
Charleston 4574324, South Carolina 4597040 29401
Contact:
Elina Bolukbasi
843-789-7816
Elina.bolukbasi@va.gov

Ralph H. Johnson VA Health Care System
Charleston 4574324, South Carolina 4597040 29401
Contact:
Susan Caulder
843-789-7816
susan.caulder@va.gov

Lowcountry Infectious Diseases, P.A.
Charleston 4574324, South Carolina 4597040 29414
Contact:
Christine Horne
718-737-3786
chorne@lcids.com

Medical University of South Carolina
Charleston 4574324, South Carolina 4597040 29425
Contact:
Alicia Hartley
843-792-4100
hartleal@musc.edu

Vanderbilt University Medical Center
Nashville 4644585, Tennessee 4662168 37232
Contact:
Emily Cleveland
615-396-0177
emily.f.cleveland@vumc.org

North Texas Infectious Disease Consultants, P.A.
Dallas 4684888, Texas 4736286 75246
Contact:
Jessica Caldwell
214-823-2533
jessica.caldwell@ntidc.org

Simcare Medical Research, LLC
Sugar Land 4734825, Texas 4736286 77478
Contact:
Armgan Khan
832-500-5184
regs@simcareresearch.com

Virginia Mason Medical Center
Seattle 5809844, Washington 5815135 98101
Contact:
Emily Chesterfield
206-341-1416
emily.chesterfield@commonspirit.org

More Details

NCT ID
NCT06237452
Status
Recruiting
Sponsor
Vedanta Biosciences, Inc.

Study Contact

Mary Garfield
857-706-1427
Consortium02-ctinquiries@vedantabio.com