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NCT06257706PHASE4Recruiting

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

Alimentiv Inc.

Start Date

8/7/2024

Completion Date

2/6/2029

Summary

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

Age Range: 18 years to 80 years

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).

Interventions

BIOLOGICAL

Vedolizumab

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Conditions

Moderately to Severely Active Crohn's DiseaseCrohn DiseaseDisease Crohn

Locations

TLC Clinical Research Inc - Los Angeles

Los Angeles, California 90048

United States

Medical University of South Carolina (MUSC)

Charleston, South Carolina 29425

United States

Houston Methodist Hospital

Houston, Texas 77030

United States

Concord Repatriation General Hospital

Concord, New South Wales 2139

Australia

Mater Misericordiae Ltd

South Brisbane, Queensland 4101

Australia

Calvary Adelaide Hospital

Adelaide, South Australia 5000

Australia

Royal Adelaide Hospital

Adelaide, South Australia 5000

Australia

The Queen Elizabeth Hospital

Woodville, South Australia 5011

Australia

Northern Hospital Epping

Epping, Victoria 3076

Australia

Austin Health

Heidelberg, Victoria 3084

Australia

The Alfred Hospital

Melbourne, Victoria 3004

Australia

Royal Melbourne Hospital

Melbourne, Victoria

Australia

Harry Perkins institute of Medical Research - Fiona Stanley Hospital

Murdoch, Western Australia 6150

Australia

VITAZ - AZ Nikolaas

Sint-Niklaas, Antwerpen 9100

Belgium

Imelda Ziekenhuis Bonheiden

Bonheiden, Antwerp 2820

Belgium

University Hospital Ghent

Ghent, East Flanders 9000

Belgium

UZ Leuven-University Hospital Gasthuisberg

Leuven, Flemish Brabant 3000

Belgium

AZ Delta - Rumbeke Campus

Roeselare, West Flanders 8800

Belgium

ULB Hopital Erasme

Brussels, 1070

Belgium

University of Calgary

Calgary, Alberta T2N 4Z6

Canada

University of Alberta, Dept of Medicine, Division of Gastroenterology

Edmonton, Alberta T6G 2X8

Canada

Viable Clinical Research - Bridgewater

Bridgewater, Nova Scotia B4V 3N2

Canada

LHSC - University Campus

London, Ontario N6A 5A5

Canada

LHSC - Victoria Hospital

London, Ontario N6A 5W9

Canada

Toronto Immune and Digestive Health Institute Inc. (TIDHI)

Toronto, Ontario

Canada

Vojenska nemocnice Brno

Brno, South Moravian 615 00

Czechia

Fakultni Nemocnice Brno

Brno, South Moravian 625 00

Czechia

Herlev Hospital

Herlev, Capital Region 2730

Denmark

Nordsjaellands Hospital - Hillerod

Hillerød, Capital Region 3400

Denmark

Bispebjerg Hospital

Copenhagen NV, Capital 2400

Denmark

Hvidovre Hospital

Hvidovre, Capital 2650

Denmark

Aarhus Universitetshospital

Aarhus, Central Denmark 8200

Denmark

Randers Regional Hospital

Randers, Central Denmark 83930

Denmark

Sjaellands Universitets hospitall Koge

Køge, Region Sjælland 4600

Denmark

Svendborg Hospital

Svendborg,

Denmark

Hopital Lyon Sud

Pierre-Bénite, Auvergne-Rhône-Alpes 69495

France

APHM

Marseille, Provence-Alpes-Côte d'Azur Region 13015

France

Groupe Hospitalier Prive Ambroise Pare - Hartmann

Neuilly-sur-Seine,

France

Universitatsklinikum Augsburg

Augsburg, Bavaria 86156

Germany

Universitatsklinkum Frankfurt - Goethe Universitat

Frankfurt am Main, Hesse 60590

Germany

Klinikum Luneburg

Lüneburg, Lower Saxony 21339

Germany

Universitaetsklinikum Schleswig-Holstein (UKSH)- Campus Kiel

Kiel, Schleswig-Holstein 24105

Germany

Universitats Klinikum Freiburg

Freiburg im Breisgau,

Germany

Ospedale Casa Sollievo della Sofferenza IRCCS

San Giovanni Rotondo, Foggia 71013

Italy

Ospedale Luigi Sacco

Milan, Lombardy 20157

Italy

Ospedale San Raffaele S.r.I.

Milan, Milan 20132

Italy

Policlinico Universitario Agostino Gemelli

Roma, Rome 00168

Italy

Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland 6525

Netherlands

Amsterdam UMC - VU Medisch Centrum

Amsterdam, North Holland 1081HV

Netherlands

Erasmus Medisch Centrum (MC)

Rotterdam, South Holland 3015 GD

Netherlands

ETZ - St. Elisabeth Hospital

Tilburg,

Netherlands

Oddzial Gastroenterologiczny SP ZOZ w Lecznej

Łęczna, Gmina Leczna 21-010

Poland

SOLUMED Centrum Medyczne

Poznan, Greater Poland Voivodeship 60-529

Poland

GASTROMED - Kopon, Zmudzinski I Wspolnicy Sp.j.

Torun, Kuyavian-Pomeranian Voivodeship 87-100

Poland

Melita Medical Sp Zoo

Wroclaw, Lower Silesian Voivodeship 53-611

Poland

Bodyclinic Sp.z.o.o. Sp.K

Warsaw, Masovia 03-712

Poland

WIP Warsaw IBD Point Profesor Kierkus

Warsaw, Masovia 04-501

Poland

Centrum Medyczne Medyk

Rzeszów, Podkarpackie Voivodeship 35-326

Poland

Vita Longa Sp. z o.o.

Katowice, Silesian 40-748

Poland

Sonomed Sp. z o.o. - Centrum Medyczne

Szczecin, West Pomerianian 71-685

Poland

Twoja Przychodnia-Centrum Medyczne Opole

Opole,

Poland

EuroMediCare (EMC) Instytut Medyczny SA

Wroclaw, 54-144

Poland

LisbonCentro Hospitalar Lisboa Norte, EPE- Hospital de Santa Maria

Lisbon,

Portugal

Nottingham University Hospitals NHS Trust - QMC

Nottingham, East Midlands NG7 2UH

United Kingdom

London North West University Healthcare NHS Trust - Northwick Park Hospital

Harrow, Middlesex HA1 3UJ

United Kingdom

Western General Hospital

Edinburgh, EH4 2XU

United Kingdom

Barts Health NHS Trust - The Royal London Hospital

London, E1 2AJ

United Kingdom

University College London Hospitals NHS Foundation Trust

London, NW1 2BU

United Kingdom

Kings College Hospital NHS Foundation Trust

London, SE5 9RS

United Kingdom