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VECTORS - A Study to Evaluate Transmural Healing as a Treatment Target in Crohn's Disease

NCT06257706 · Alimentiv Inc.
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Official title
An Interventional Study to Evaluate Treating to a Target of Transmural Healing in Patients With Moderately to Severely Active Crohn's Disease
About this study
Transmural healing (TMH) is recognized as a potentially important measure of Crohn's disease (CD) activity but not a formal target. Observational studies suggest that TMH may be associated with better long-term outcomes. The study will evaluate TMH using noninvasive intestinal ultrasound (IUS), a patient-friendly technique that can be performed routinely in clinical practice. The aim of the study is to determine if treating to a target of corticosteroid-free (CS-free) IUS outcomes + clinical symptoms + biomarkers is superior to a target of clinical symptoms + biomarkers alone in achieving CS-free endoscopic remission measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD). Qualified participants will be randomly assigned in a 1:1 ratio to one of 2 different target treatment groups. Group 1: Participants will be treated over 48 weeks to achieve a target of corticosteroid-free IUS-based outcomes + clinical remission + biomarker remission. At Week 22 and 30, the IUS-based component of the target will be IUS response and at Week 38, the final treatment target will be TMH. Group 2: Participants will be treated over 48 weeks to achieve a target of corticosteroid-free clinical remission + biomarker remission.
Eligibility criteria
Inclusion Criteria: 1. Adults aged 18 to 80 years, inclusive, at the time of consent; 2. Moderately to severely active CD at baseline defined by a CDAI score of 220 to 450 inclusive and SES-CD, excluding the presence of narrowing component, ≥6 (or ≥4 for participants with isolated ileal disease); 3. BWT on IUS of \>4.0 mm in the terminal ileum or any colonic segment (excluding the rectum) as assessed by the mean of 2 longitudinal and 2 cross-sectional measurements of the same segment; 4. Biologic-naïve or have previous exposure (within the last 5 years of the screening date) to no more than 1 advanced therapeutic compound (approved biologic or small molecule drug) for the treatment of their CD. Note: only approximately 15% to 30% of the enrolled population will have had prior exposure to an advanced therapeutic; 5. Participants may continue stable dose (initiated at least 4 weeks prior to Screening) of 5-ASA for CD; 6. Persons of childbearing potential must have a negative serum pregnancy test prior to randomization and must use a highly effective method of contraception throughout the study. Females unable to bear children must have documentation of such in the source records; 7. Able to participate fully in all aspects of this clinical trial; 8. Written informed consent must be obtained and documented. Exclusion Criteria: 1. Current or previous treatment with vedolizumab, etrolizumab, or natalizumab; 2. Previously exposed to 2 or more compounds or classes of an advanced therapeutic compound (approved biologic or small molecule drug) for the treatment of their CD; 3. Change to oral corticosteroid therapy dosing within 2 weeks prior to randomization or a corticosteroid dose of \>40 mg of prednisone or equivalent at randomization; 4. Only have inflammation proximal to the terminal ileum that cannot be reached by ileocolonoscopy; 5. Have a CD complication, such as symptomatic strictures in the small bowel with \>3 cm prestenotic dilatation on any imaging modality, requiring procedural intervention; 6. Previous extensive colonic resection or missing \>2 segments out of 5 (terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum), ileorectal anastomosis, or a proctocolectomy; 7. Ostomy or ileoanal pouch; 8. Short bowel syndrome; 9. Fibrotic-only stricture in the ileum or colon without evidence of active inflammation (in the investigator's judgment), including any impassable stenosis; 10. Abscess \>2 cm, detected by IUS or endoscopy; participants with draining fistulas are not excluded; 11. Serious underlying disease other than CD that, in the opinion of the investigator, may interfere with the participant's ability to participate fully in the study or would compromise participant safety; 12. Positive stool test for Clostridioides difficile infection (as demonstrated by positive toxin); 13. Known HIV or hepatitis B or C infection. If a negative test result is available in the 12 months prior to randomization, retesting is not required; 14. Known active or latent tuberculosis (TB); if a negative test result is available in the 12 months prior to randomization, confirmatory testing (per standard of care) is not required before randomization; 15. Other systemic or opportunistic infection (including cytomegalovirus), any other clinically significant extraintestinal infection, or recurring infection within 6 months of randomization; 16. Has active cerebral/meningeal disease, signs, symptoms, or any history of progressive multifocal leukoencephalopathy (PML) prior to randomization; 17. Hypersensitivity, allergy, or intolerance to any excipient of vedolizumab or any other contraindication to vedolizumab; 18. Active severe infection such as sepsis, cytomegalovirus, listeriosis, or opportunistic infection. 19. Unwillingness to withhold protocol-prohibited medications during the trial; 20. Concurrent or previous participation in another clinical trial and received any investigational therapy within 30 days prior to randomization; 21. History of alcohol or drug abuse that in the opinion of the investigator may interfere with the participant's ability to comply with the study procedures; 22. Prior enrolment in the current study and had received study treatment; 23. Pregnant, lactating, or intending to become pregnant/impregnate a partner before, during, or within 18 weeks after the last dose; or intending to donate ova or sperm during such time period; 24. Vaccination with a live or live-attenuated vaccine within 4 weeks prior to randomization, or planned vaccination with a live or live-attenuated vaccine during participation in the study; 25. Any person performing mandatory military service, deprived of liberty, in a residential care setting, or any person who, due to a judicial decision, cannot take part in clinical studies; 26. The person is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling).
Study design
Enrollment target: 304 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-08-07
Estimated completion: 2029-02-06
Last updated: 2026-01-15
Interventions
Biological: Vedolizumab
Primary outcomes
  • Percentage of participants with Corticosteroid-free Endoscopic remission in group 1 and group 2 at week 48 (week 48)
Sponsor
Alimentiv Inc. · other
With: Takeda
Contacts & investigators
ContactElena van Hest · contact · elena.vanhest@alimentiv.com · 31205630316
InvestigatorVipul Jairath, MD · principal_investigator, Alimentiv Inc.
All locations (69)
TLC Clinical Research Inc - Los AngelesWithdrawn
Los Angeles, California, United States
Medical University of South Carolina (MUSC)Not Yet Recruiting
Charleston, South Carolina, United States
Houston Methodist HospitalRecruiting
Houston, Texas, United States
Concord Repatriation General HospitalRecruiting
Concord, New South Wales, Australia
Mater Misericordiae LtdRecruiting
South Brisbane, Queensland, Australia
Calvary Adelaide HospitalRecruiting
Adelaide, South Australia, Australia
Royal Adelaide HospitalRecruiting
Adelaide, South Australia, Australia
The Queen Elizabeth HospitalRecruiting
Woodville, South Australia, Australia
Northern Hospital EppingRecruiting
Epping, Victoria, Australia
Austin HealthRecruiting
Heidelberg, Victoria, Australia
The Alfred HospitalRecruiting
Melbourne, Victoria, Australia
Royal Melbourne HospitalRecruiting
Melbourne, Victoria, Australia
Harry Perkins institute of Medical Research - Fiona Stanley HospitalRecruiting
Murdoch, Western Australia, Australia
VITAZ - AZ NikolaasRecruiting
Sint-Niklaas, Antwerpen, Belgium
Imelda Ziekenhuis BonheidenRecruiting
Bonheiden, Antwerp, Belgium
University Hospital GhentRecruiting
Ghent, East Flanders, Belgium
UZ Leuven-University Hospital GasthuisbergRecruiting
Leuven, Flemish Brabant, Belgium
AZ Delta - Rumbeke CampusRecruiting
Roeselare, West Flanders, Belgium
ULB Hopital ErasmeRecruiting
Brussels, Belgium
University of CalgaryRecruiting
Calgary, Alberta, Canada
University of Alberta, Dept of Medicine, Division of GastroenterologyRecruiting
Edmonton, Alberta, Canada
Viable Clinical Research - BridgewaterRecruiting
Bridgewater, Nova Scotia, Canada
LHSC - University CampusRecruiting
London, Ontario, Canada
LHSC - Victoria HospitalNot Yet Recruiting
London, Ontario, Canada
Toronto Immune and Digestive Health Institute Inc. (TIDHI)Recruiting
Toronto, Ontario, Canada
Vojenska nemocnice BrnoNot Yet Recruiting
Brno, South Moravian, Czechia
Fakultni Nemocnice BrnoNot Yet Recruiting
Brno, South Moravian, Czechia
Herlev HospitalRecruiting
Herlev, Capital Region, Denmark
Nordsjaellands Hospital - HillerodRecruiting
Hillerød, Capital Region, Denmark
Bispebjerg HospitalRecruiting
Copenhagen NV, Capital, Denmark
Hvidovre HospitalRecruiting
Hvidovre, Capital, Denmark
Aarhus UniversitetshospitalRecruiting
Aarhus, Central Denmark, Denmark
Randers Regional HospitalRecruiting
Randers, Central Denmark, Denmark
Sjaellands Universitets hospitall KogeWithdrawn
Køge, Region Sjælland, Denmark
Svendborg HospitalWithdrawn
Svendborg, Denmark
Hopital Lyon SudRecruiting
Pierre-Bénite, Auvergne-Rhône-Alpes, France
APHMRecruiting
Marseille, Provence-Alpes-Côte d'Azur Region, France
Groupe Hospitalier Prive Ambroise Pare - HartmannWithdrawn
Neuilly-sur-Seine, France
Universitatsklinikum AugsburgNot Yet Recruiting
Augsburg, Bavaria, Germany
Universitatsklinkum Frankfurt - Goethe UniversitatWithdrawn
Frankfurt am Main, Hesse, Germany
Klinikum LuneburgRecruiting
Lüneburg, Lower Saxony, Germany
Universitaetsklinikum Schleswig-Holstein (UKSH)- Campus KielRecruiting
Kiel, Schleswig-Holstein, Germany
Universitats Klinikum FreiburgWithdrawn
Freiburg im Breisgau, Germany
Ospedale Casa Sollievo della Sofferenza IRCCSRecruiting
San Giovanni Rotondo, Foggia, Italy
Ospedale Luigi SaccoRecruiting
Milan, Lombardy, Italy
Ospedale San Raffaele S.r.I.Not Yet Recruiting
Milan, Milan, Italy
Policlinico Universitario Agostino GemelliRecruiting
Roma, Rome, Italy
Radboud University Nijmegen Medical CentreRecruiting
Nijmegen, Gelderland, Netherlands
Amsterdam UMC - VU Medisch CentrumRecruiting
Amsterdam, North Holland, Netherlands
Erasmus Medisch Centrum (MC)Not Yet Recruiting
Rotterdam, South Holland, Netherlands
ETZ - St. Elisabeth HospitalWithdrawn
Tilburg, Netherlands
Oddzial Gastroenterologiczny SP ZOZ w LecznejRecruiting
Łęczna, Gmina Leczna, Poland
SOLUMED Centrum MedyczneRecruiting
Poznan, Greater Poland Voivodeship, Poland
GASTROMED - Kopon, Zmudzinski I Wspolnicy Sp.j.Recruiting
Torun, Kuyavian-Pomeranian Voivodeship, Poland
Melita Medical Sp ZooRecruiting
Wroclaw, Lower Silesian Voivodeship, Poland
Bodyclinic Sp.z.o.o. Sp.KRecruiting
Warsaw, Masovia, Poland
WIP Warsaw IBD Point Profesor KierkusRecruiting
Warsaw, Masovia, Poland
Centrum Medyczne MedykRecruiting
Rzeszów, Podkarpackie Voivodeship, Poland
Vita Longa Sp. z o.o.Recruiting
Katowice, Silesian, Poland
Sonomed Sp. z o.o. - Centrum MedyczneRecruiting
Szczecin, West Pomerianian, Poland
Twoja Przychodnia-Centrum Medyczne OpoleWithdrawn
Opole, Poland
EuroMediCare (EMC) Instytut Medyczny SARecruiting
Wroclaw, Poland
LisbonCentro Hospitalar Lisboa Norte, EPE- Hospital de Santa MariaNot Yet Recruiting
Lisbon, Portugal
Nottingham University Hospitals NHS Trust - QMCRecruiting
Nottingham, East Midlands, United Kingdom
London North West University Healthcare NHS Trust - Northwick Park HospitalWithdrawn
Harrow, Middlesex, United Kingdom
Western General HospitalNot Yet Recruiting
Edinburgh, United Kingdom
Barts Health NHS Trust - The Royal London HospitalRecruiting
London, United Kingdom
University College London Hospitals NHS Foundation TrustRecruiting
London, United Kingdom
Kings College Hospital NHS Foundation TrustRecruiting
London, United Kingdom
VECTORS - A Study to Evaluate Transmural Healing as a Treatment Target in Crohn's Disease · TrialPath