Crohn's Disease
Conditions
Keywords
Vedolizumab, Corticosteroids, Prednisone, Crohn's disease
Brief summary
Use of co-induction with corticosteroid therapies may accelerate the remission rate when used with vedolizumab. Further, this may lead to higher rates of response and remission at week 10 than would be seen with vedolizumab monotherapy.
Detailed description
This study will examine prednisone co-induction with vedolizumab in patients with Crohn's disease. To address questions regarding the effect of co-induction on mucosal healing, the study will include colonoscopic assessment of mucosal healing. Finally, colonic biopsies in this study will allow to elucidate further the mechanism of action of vedolizumab in Crohn's disease through immune phenotyping studies.
Interventions
DRUGPrednisone
DRUGPlacebo
DRUGVedolizumab
300mg IV over 30 minutes. Both arms will receive vedolizumab at weeks 0, 2, and 6.
Sponsors
Takeda
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age at entry 18 to 70 * CDAI score \> 220 * Concomitant azathioprine, methotrexate, or mercaptopurine permitted if dose has been stable for \> 8 weeks. Prior anti-TNFα antibody use permitted but must be discontinued (\>2 weeks from last dose) prior to initiation of vedolizumab. * Documented ulceration on colonoscopy done at screening of 3 or more large ulcers or 10 or more aphthous ulcers * Able to provide written informed consent. * Patient is planned for or eligible to initiate vedolizumab
Exclusion criteria
* Concurrent use of anti-TNFα antibodies. * No corticosteroids within prior 3 months (other than budesonide controlled ileal release) * No stoma at the time of enrollment * No absolute contraindication to systemic corticosteroid use such as hypersensitivity to any part of the formulation, systemic fungal infection, or recent administration of live or live attenuated vaccine within prior two weeks. * Pregnant women or plans for pregnancy within 3 months of study inclusion * Presence of stoma, more than three small-bowel resections, or documented history of short bowel syndrome * Intestinal stricture requiring surgery * Abdominal abscess * Inability or unwillingness to provide informed consent * Any other condition, which, in the opinion of the investigators would impede competence or compliance or possibly hinder completion of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Crohn's Disease Activity Index (CDAI) | baseline, week 6, week 10 | Clinical remission, defined as CDAI \< 150, in group with steroid co-induction vs. placebo co-induction. The purpose of this crohn's disease activity index (CDAI) calculator is to gauge the progress or lack of progress for people with crohn's disease. CDAI scores below 150 indicate a better prognosis than higher scores |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Simple Endoscopic Score for Crohn's Disease (SES-CD) | baseline and week 10 | The SES-CD tool is used to quantify and compare inflammatory load. The Simple Endoscopic Score for Crohn Disease (SES-CD) assesses the size of mucosal ulcers, the ulcerated surface, the endoscopic extension and the presence of stenosis. Each item is scored from 0-3, with total score from 0-60. Higher score indicates more severe endoscopic activity. |
| Change in C-Reactive Protein (CRP) | baseline and week 10 | Comparison of absolute change in CRP from baseline to week 10. C-reactive protein is produced by the liver. The level of CRP rises when there is inflammation throughout the body. |
| Change in Calprotectin | baseline, week 6 and week 10 | Comparison of absolute change in calprotectin from baseline to week 6. Calprotectin is a stool (fecal) test that is used to detect inflammation in the intestines. |
Countries
United States
Participant flow
Recruitment details
Study opened in August 2015,and one participant enrolled almost a year later.
Pre-assignment details
Study is double blind and unknown which arm participant was randomized into. Study was never unblinded.
Participants by arm
| Arm | Count |
|---|---|
| Prednisone Co-inductive Therapy Prednisone vs Identical placebo taper
Prednisone 40 mg/day starting at week 0 for 2 weeks, tapered by 10 mg weekly to achieve 0 mg by end of week 5
Vedolizumab: 300mg IV over 30 minutes. Both arms will receive vedolizumab at weeks 0, 2, and 6. | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | study terminated | 1 |
Baseline characteristics
| Characteristic | Prednisone Co-inductive Therapy | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 1 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 1 Participants | — |
| Sex: Female, Male Male | 0 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Crohn's Disease Activity Index (CDAI)
Clinical remission, defined as CDAI \< 150, in group with steroid co-induction vs. placebo co-induction. The purpose of this crohn's disease activity index (CDAI) calculator is to gauge the progress or lack of progress for people with crohn's disease. CDAI scores below 150 indicate a better prognosis than higher scores
Time frame: baseline, week 6, week 10
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prednisone Co-inductive Therapy | Crohn's Disease Activity Index (CDAI) | Baseline | 263 score on a scale |
| Prednisone Co-inductive Therapy | Crohn's Disease Activity Index (CDAI) | Week 6 | 112.6 score on a scale |
| Prednisone Co-inductive Therapy | Crohn's Disease Activity Index (CDAI) | Week 10 | 137.5 score on a scale |
Secondary
Change in Calprotectin
Comparison of absolute change in calprotectin from baseline to week 6. Calprotectin is a stool (fecal) test that is used to detect inflammation in the intestines.
Time frame: baseline, week 6 and week 10
Population: data not collected
Secondary
Change in C-Reactive Protein (CRP)
Comparison of absolute change in CRP from baseline to week 10. C-reactive protein is produced by the liver. The level of CRP rises when there is inflammation throughout the body.
Time frame: baseline and week 10
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prednisone Co-inductive Therapy | Change in C-Reactive Protein (CRP) | baseline | 11.0 mg/L |
| Prednisone Co-inductive Therapy | Change in C-Reactive Protein (CRP) | week 10 | 43.0 mg/L |
Secondary
Change in Simple Endoscopic Score for Crohn's Disease (SES-CD)
The SES-CD tool is used to quantify and compare inflammatory load. The Simple Endoscopic Score for Crohn Disease (SES-CD) assesses the size of mucosal ulcers, the ulcerated surface, the endoscopic extension and the presence of stenosis. Each item is scored from 0-3, with total score from 0-60. Higher score indicates more severe endoscopic activity.
Time frame: baseline and week 10
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prednisone Co-inductive Therapy | Change in Simple Endoscopic Score for Crohn's Disease (SES-CD) | Baseline | 24 score on a scale |
| Prednisone Co-inductive Therapy | Change in Simple Endoscopic Score for Crohn's Disease (SES-CD) | Week 10 | 18 score on a scale |