Recruiting
Phase 4
VECTORS - A Study to Evaluate Transmural Healing as a Treatment Target in Crohn's Disease
Condition(s) studied
Moderately to Severely Active Crohn's DiseaseCrohn DiseaseDisease Crohn
Investigational drug(s) / intervention(s)
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.
Study 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
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).
Primary outcome measure(s)
- Percentage of participants with Corticosteroid-free Endoscopic remission in group 1 and group 2 at week 48 — week 48
Corticosteroid-free is defined as not using corticosteroids at the time of the assessment. Endoscopic remission is defined by a total Simple Endoscopic Score for CD (SES-CD) ≤4 and at least a 2-point reduction versus baseline with no subscore greater than 1 in any individual variable. The SES-CD scores 4 endoscopic items (ulcer size, proportion of ulcerated surface, proportion of the surface area affected by any disease lesion, and stenosis) from 0 to 3, with higher scores representing more severe endoscopic disease activity. Each variable is scored for the 5 intestinal segments (ileum, right colon, transverse colon, left colon, and rectum) and summed to provide the total variable score. The sum of each variable score ranges from 0 to 15, except for stenosis (ranges from 0 to 11), because 3 represents a stenosis through which a colonoscope cannot be passed and therefore, can only be observed once. Total SES-CD score is then calculated by summing the item scores (range, 0-56 points).
Trial sites (69)
| Facility | City | Region | Status |
| TLC Clinical Research Inc - Los Angeles |
Los Angeles |
California |
Withdrawn |
| Medical University of South Carolina (MUSC) |
Charleston |
South Carolina |
Not Yet Recruiting |
| Houston Methodist Hospital |
Houston |
Texas |
Recruiting |
| Concord Repatriation General Hospital |
Concord |
New South Wales |
Recruiting |
| Mater Misericordiae Ltd |
South Brisbane |
Queensland |
Recruiting |
| Calvary Adelaide Hospital |
Adelaide |
South Australia |
Recruiting |
| Royal Adelaide Hospital |
Adelaide |
South Australia |
Recruiting |
| The Queen Elizabeth Hospital |
Woodville |
South Australia |
Recruiting |
| Northern Hospital Epping |
Epping |
Victoria |
Recruiting |
| Austin Health |
Heidelberg |
Victoria |
Recruiting |
| The Alfred Hospital |
Melbourne |
Victoria |
Recruiting |
| Royal Melbourne Hospital |
Melbourne |
Victoria |
Recruiting |
| Harry Perkins institute of Medical Research - Fiona Stanley Hospital |
Murdoch |
Western Australia |
Recruiting |
| VITAZ - AZ Nikolaas |
Sint-Niklaas |
Antwerpen |
Recruiting |
| Imelda Ziekenhuis Bonheiden |
Bonheiden |
Antwerp |
Recruiting |
| University Hospital Ghent |
Ghent |
East Flanders |
Recruiting |
| UZ Leuven-University Hospital Gasthuisberg |
Leuven |
Flemish Brabant |
Recruiting |
| AZ Delta - Rumbeke Campus |
Roeselare |
West Flanders |
Recruiting |
| ULB Hopital Erasme |
Brussels |
Belgium |
Recruiting |
| University of Calgary |
Calgary |
Alberta |
Recruiting |
| University of Alberta, Dept of Medicine, Division of Gastroenterology |
Edmonton |
Alberta |
Recruiting |
| Viable Clinical Research - Bridgewater |
Bridgewater |
Nova Scotia |
Recruiting |
| LHSC - University Campus |
London |
Ontario |
Recruiting |
| LHSC - Victoria Hospital |
London |
Ontario |
Not Yet Recruiting |
| Toronto Immune and Digestive Health Institute Inc. (TIDHI) |
Toronto |
Ontario |
Recruiting |
| Vojenska nemocnice Brno |
Brno |
South Moravian |
Not Yet Recruiting |
| Fakultni Nemocnice Brno |
Brno |
South Moravian |
Not Yet Recruiting |
| Herlev Hospital |
Herlev |
Capital Region |
Recruiting |
| Nordsjaellands Hospital - Hillerod |
Hillerød |
Capital Region |
Recruiting |
| Bispebjerg Hospital |
Copenhagen NV |
Capital |
Recruiting |
| Hvidovre Hospital |
Hvidovre |
Capital |
Recruiting |
| Aarhus Universitetshospital |
Aarhus |
Central Denmark |
Recruiting |
| Randers Regional Hospital |
Randers |
Central Denmark |
Recruiting |
| Sjaellands Universitets hospitall Koge |
Køge |
Region Sjælland |
Withdrawn |
| Svendborg Hospital |
Svendborg |
Denmark |
Withdrawn |
| Hopital Lyon Sud |
Pierre-Bénite |
Auvergne-Rhône-Alpes |
Recruiting |
| APHM |
Marseille |
Provence-Alpes-Côte d'Azur Region |
Recruiting |
| Groupe Hospitalier Prive Ambroise Pare - Hartmann |
Neuilly-sur-Seine |
France |
Withdrawn |
| Universitatsklinikum Augsburg |
Augsburg |
Bavaria |
Not Yet Recruiting |
| Universitatsklinkum Frankfurt - Goethe Universitat |
Frankfurt am Main |
Hesse |
Withdrawn |
+ 29 more sites — see the full list on the official registry below.
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