VECTORS - A Study to Evaluate Transmural Healing as a Treatment Target in Crohn's Disease
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-80
SponsorAlimentiv Inc.
About this trial
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
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
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;
Trial design
Design model
Parallel
Treatments tested in this trial
Vedolizumab
Biological/VaccineAll 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.
Treatment groups
304 Participants
are divided into 2 treatment groupsGroup A: Group 1: Corticosteroid-free IUS-based outcomes + clinical remission + biomarker remissionOther 1 intervention
Group B: Group 2: Corticosteroid-free clinical remission + biomarker remission.Other 1 intervention
Trial outcomes
Primary outcomes
1
Percentage of participants with Corticosteroid-free Endoscopic remission in group 1 and group 2 at 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).
Time frame
week 48Secondary outcomes
1
Percentage of participants with Corticosteroid-free Transmural healing (TMH)+Endoscopic remission+Clinical remission in group 1 and group 2 at week 48
Transmural healing is defined by Bowel wall thickness (BWT) ≤3.0 mm and color Doppler signal (CDS) 0 in all evaluable segments assessed by Intestinal Ultrasound. Endoscopic remission is defined by achievement of 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 assesses 4 endoscopic variables: the size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each variable score ranging from 0 to 3. The total SES-CD score is calculated using the sum of all parameter scores in 5 segments: terminal ileum, right colon, transverse colon, left colon, and rectum. Clinical Remission is defined by achievement of Crohn's Disease Activity Index (CDAI) \<150. CDAI consists of eight factors, each summed after adjustment with a weighting factor. Total score ranges from 0 to 600 points. Higher scores indicate more severity.
Time frame
week 482
Percentage of participants with Corticosteroid-free IUS response+Endoscopic remission+Clinical Remission in group 1 and group 2 at week 48
IUS response is defined by reduction from baseline of 25% in Bowel Wall thickness (BWT) assessed by Intestinal Ultrasound (IUS). Endoscopic remission is defined by achievement of 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. Clinical Remission is defined by achievement of Crohn's Disease Activity Index (CDAI) \<150. The CDAI consists of 8 items including physical examination items, extraintestinal manifestations, the hematocrit, and PRO measures as recorded in the participant diary card for the 7 days prior to the clinic visit. Each item is multiplied by a weighting factor and summed to give a total CDAI score, ranging from 0 to over 600 points, with higher scores representing more severe disease activity.
Time frame
week 483
Percentage of participants with Corticosteroid-free Endoscopic remission+Clinical Remission in group 1 and group 2 at week 48
Endoscopic remission is defined by achievement of 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. 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. Total SES-CD score is then summed up the item scores (range, 0-56 points). Clinical Remission is defined by Crohn's Disease Activity Index (CDAI) \<150. CDAI consists of eight factors, each summed after adjustment with a weighting factor. Total score ranges from 0 to 600 points. Higher scores indicate more severity.
Time frame
week 484
Percentage of participants with Corticosteroid-free endoscopic response+Clinical response in group 1 and group 2 at week 48
Endoscopic response is defined by Reduction in total Simple Endoscopic Score for CD (SES-CD) ≥50% from baseline. 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, higher scores indicate more severity. 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, where it ranges from 0 to 11. Total SES-CD score is then calculated by summing the item scores (range, 0-56 points). Clinical Response is defined by Crohn's Disease Activity Index (CDAI) decrease of ≥100 points from baseline. CDAI consists of eight factors, each summed after adjustment with a weighting factor. Total score ranges from 0 to 600 points. Higher scores indicate more severity.
Time frame
week 48Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Alimentiv Inc.
Lead sponsor
Takeda
Collaborator
Source ClinicalTrials.gov