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

Official title

An Interventional Study to Evaluate Treating to a Target of Transmural Healing in Patients With Moderately to Severely Active Crohn's Disease

Overview

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.

Interventions

• Biological Vedolizumab
  All participants will begin a vedolizumab induction regimen of 300 mg IV at Weeks 0, 2, 6, and 10 followed by vedolizumab 300 mg IV every 8 weeks starting at Week 14. Treatment may be modified at Weeks 22, 30, and/or 38 based on the results of the target assessment at each of these time points.

Primary outcome measures

• Percentage of participants with Corticosteroid-free Endoscopic remission in group 1 and group 2 at week 48 [Time frame: week 48]

Secondary outcome measures (12)

• Percentage of participants with Corticosteroid-free Transmural healing (TMH)+Endoscopic remission+Clinical remission in group 1 and group 2 at week 48 [Time frame: week 48]
• Percentage of participants with Corticosteroid-free IUS response+Endoscopic remission+Clinical Remission in group 1 and group 2 at week 48 [Time frame: week 48]
• Percentage of participants with Corticosteroid-free Endoscopic remission+Clinical Remission in group 1 and group 2 at week 48 [Time frame: week 48]
• Percentage of participants with Corticosteroid-free endoscopic response+Clinical response in group 1 and group 2 at week 48 [Time frame: week 48]
• Percentage of participants with Corticosteroid-free clinical remission in group 1 and group 2 at Week 14, Week 22 and Week 48. [Time frame: week 14, week 22 and week 48]
• Percentage of participants with Corticosteroid-free Clinical Response in group 1 and group 2 at week 14, week 22 and week 48 [Time frame: week 14, week 22 and week 48]
• Crohn's Disease Activity Index(CDAI) total score and corresponding change from baseline during follow-up (Week 6, Week 14, Week 22, Week 30, Week 38, Week 48, Week 64, Week 80, Week 96) in group 1 and group 2 [Time frame: week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96]
• Percentage of participants with Corticosteroid-free endoscopic response in group 1 and group 2 at week 48 [Time frame: week 48]
• SES-CD total score and corresponding change from baseline to Week 48 in group 1 and group 2 [Time frame: week 48]
• Percentage of participants with Transmural healing (TMH) in group 1 and group 2 at week 48 [Time frame: week 48]
• Percentage of participants with Intestinal Ultrasound (IUS) response in group 1 and group 2 at Week 48 [Time frame: week 48]
• Bowel Wall Thickness (BWT) measured by Intestinal Ultrasound (IUS) in mm and corresponding change from baseline at Week 48 in group 1 and group 2. [Time frame: week 48]

Eligibility criteria

Inclusion criteria

• Adults aged 18 to 80 years, inclusive, at the time of consent;
• 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);
• 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;
• 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;
• Participants may continue stable dose (initiated at least 4 weeks prior to Screening) of 5-ASA for CD;
• 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;
• Able to participate fully in all aspects of this clinical trial;
• Written informed consent must be obtained and documented.

Exclusion criteria

• Current or previous treatment with vedolizumab, etrolizumab, or natalizumab;
• 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;
• 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;
• Only have inflammation proximal to the terminal ileum that cannot be reached by ileocolonoscopy;
• Have a CD complication, such as symptomatic strictures in the small bowel with >3 cm prestenotic dilatation on any imaging modality, requiring procedural intervention;
• 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;
• Ostomy or ileoanal pouch;
• Short bowel syndrome;
• Fibrotic-only stricture in the ileum or colon without evidence of active inflammation (in the investigator's judgment), including any impassable stenosis;
• Abscess >2 cm, detected by IUS or endoscopy; participants with draining fistulas are not excluded;
• 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;
• Positive stool test for Clostridioides difficile infection (as demonstrated by positive toxin);
• 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;
• 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;
• Other systemic or opportunistic infection (including cytomegalovirus), any other clinically significant extraintestinal infection, or recurring infection within 6 months of randomization;
• Has active cerebral/meningeal disease, signs, symptoms, or any history of progressive multifocal leukoencephalopathy (PML) prior to randomization;
• Hypersensitivity, allergy, or intolerance to any excipient of vedolizumab or any other contraindication to vedolizumab;
• Active severe infection such as sepsis, cytomegalovirus, listeriosis, or opportunistic infection.
• Unwillingness to withhold protocol-prohibited medications during the trial;
• Concurrent or previous participation in another clinical trial and received any investigational therapy within 30 days prior to randomization;
• 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;
• Prior enrolment in the current study and had received study treatment;
• 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;
• 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;
• 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;
• 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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Poland · 11 centers

• Oddzial Gastroenterologiczny SP ZOZ w Lecznej — Łęczna
• SOLUMED Centrum Medyczne — Poznan
• GASTROMED - Kopon, Zmudzinski I Wspolnicy Sp.j. — Torun
• Melita Medical Sp Zoo — Wroclaw
• Bodyclinic Sp.z.o.o. Sp.K — Warsaw
• WIP Warsaw IBD Point Profesor Kierkus — Warsaw
• Centrum Medyczne Medyk — Rzeszów
• Vita Longa Sp. z o.o. — Katowice
• … and 3 more centers

Australia · 10 centers

• Concord Repatriation General Hospital — Concord
• Mater Misericordiae Ltd — South Brisbane
• Calvary Adelaide Hospital — Adelaide
• Royal Adelaide Hospital — Adelaide
• The Queen Elizabeth Hospital — Woodville
• Northern Hospital Epping — Epping
• Austin Health — Heidelberg
• The Alfred Hospital — Melbourne
• … and 2 more centers

Denmark · 8 centers

• Herlev Hospital — Herlev
• Nordsjaellands Hospital - Hillerod — Hillerød
• Bispebjerg Hospital — Copenhagen NV
• Hvidovre Hospital — Hvidovre
• Aarhus Universitetshospital — Aarhus
• Randers Regional Hospital — Randers
• Sjaellands Universitets hospitall Koge — Køge
• Svendborg Hospital — Svendborg

Belgium · 6 centers

• VITAZ - AZ Nikolaas — Sint-Niklaas
• Imelda Ziekenhuis Bonheiden — Bonheiden
• University Hospital Ghent — Ghent
• UZ Leuven-University Hospital Gasthuisberg — Leuven
• AZ Delta - Rumbeke Campus — Roeselare
• ULB Hopital Erasme — Brussels

Canada · 6 centers

• University of Calgary — Calgary
• University of Alberta, Dept of Medicine, Division of Gastroenterology — Edmonton
• Viable Clinical Research - Bridgewater — Bridgewater
• LHSC - University Campus — London
• LHSC - Victoria Hospital — London
• Toronto Immune and Digestive Health Institute Inc. (TIDHI) — Toronto

United Kingdom · 6 centers

• Nottingham University Hospitals NHS Trust - QMC — Nottingham
• London North West University Healthcare NHS Trust - Northwick Park Hospital — Harrow
• Western General Hospital — Edinburgh
• Barts Health NHS Trust - The Royal London Hospital — London
• University College London Hospitals NHS Foundation Trust — London
• Kings College Hospital NHS Foundation Trust — London

Germany · 5 centers

• Universitatsklinikum Augsburg — Augsburg
• Universitatsklinkum Frankfurt - Goethe Universitat — Frankfurt am Main
• Klinikum Luneburg — Lüneburg
• Universitaetsklinikum Schleswig-Holstein (UKSH)- Campus Kiel — Kiel
• Universitats Klinikum Freiburg — Freiburg im Breisgau

Italy · 4 centers

• Ospedale Casa Sollievo della Sofferenza IRCCS — San Giovanni Rotondo
• Ospedale Luigi Sacco — Milan
• Ospedale San Raffaele S.r.I. — Milan
• Policlinico Universitario Agostino Gemelli — Roma

Netherlands · 4 centers

• Radboud University Nijmegen Medical Centre — Nijmegen
• Amsterdam UMC - VU Medisch Centrum — Amsterdam
• Erasmus Medisch Centrum (MC) — Rotterdam
• ETZ - St. Elisabeth Hospital — Tilburg

United States · 3 centers

• TLC Clinical Research Inc - Los Angeles — Los Angeles
• Medical University of South Carolina (MUSC) — Charleston
• Houston Methodist Hospital — Houston

France · 3 centers

• Hopital Lyon Sud — Pierre-Bénite
• APHM — Marseille
• Groupe Hospitalier Prive Ambroise Pare - Hartmann — Neuilly-sur-Seine

Czechia · 2 centers

• Vojenska nemocnice Brno — Brno
• Fakultni Nemocnice Brno — Brno

Portugal · 1 center

• LisbonCentro Hospitalar Lisboa Norte, EPE- Hospital de Santa Maria — Lisbon

Publications

• Jairath V, Vuyyuru SK, Zou G, Ma C, Neustifter B, Agboton C, Romo Bautista I, Allocca M, An YK, Begun J, Bryant RV, Danese S, Dubinsky M, Feagan BG, Freire M, Novak KL, Panaccione R, Pudipeddi A, Rubin DT, Sands BE, Sparrow MP, Taylor SA, Gecse KB, Wilkens R, Maaser C. Evaluating treatment to a target of transmural healing in patients with moderately to severely active Crohn's disease: rationale, PMID 41720589

Identifiers

NCT: NCT06257706 · TAK01769

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗