Crohn Disease of Small Intestine
Conditions
Brief summary
The overall goal of the study is to develop data that can convincingly guide clinicians on the use and efficacy of vedolizumab in patients with small bowel CD. There is an unmet need to identify response to vedolizumab in small bowel CD using objective endpoints. Current data suggest that MR enterography may meet this unmet need. There is an additional unmet need to develop predictive models incorporating both clinical and baseline radiological and endoscopic variables with higher discriminatory performance in identifying longer term clinical remission with vedolizumab. Finally, this proposal is strengthened by the exploratory studies which may identify new proteomic biomarkers that correlate with longer term radiological response with vedolizumab reflecting its latency of response. If successful, these serum biomarkers may guide a personalized approach to the treatment of small bowel CD with vedolizumab, allowing early identification of PNR, monitoring disease activity and the pharmacodynamics of vedolizumab.
Interventions
Vedolizumab Injection
Sponsors
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Moderate to severe disease activity small bowel CD (small bowel only or ileocecal only) visible on MRE * Initiated on Vedolizumab with/without thiopurines or methotrexate * ≥18 years old
Exclusion criteria
* Pregnancy * Age \<18 * Planned surgery prior to the first follow-up MRE * Inability to provide informed consent. * Perianal CD will be excluded since assessment requires performance of additional MRI of the pelvis. * Individuals with colonic involvement other than involvement of the ascending colon and cecum. * Inpatient scans will only be included if this is a MRE and adequate small bowel distension with appropriate contrast has been achieved * If unable to provide informed consent * Contraindications for MRE including chronic kidney disease that precludes contrast administration, implanted medical devices that are contraindicated for MRE.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiological Response | 24±2 weeks | Radiological Transmural Response will be defined per-lesion and per-patient. Per-lesion TR will be defined as a decrease in the length of inflamed small bowel lesion from baseline or improvement in any imaging findings associated with severe mural inflammation, i.e., restricted diffusion, mural thickness, intramural T2 hyperintensity, peri-enteric T2 signal, and luminal ulcerations, without development of a new penetrating or stricturing complication. Worsened lesions will be fined as those with an increased score of any imaging parameter associated with severe mural inflammation. Unchanged lesions will be defined as those with unchanged (without worsening or improving) inflammatory parameters associated with severe mural inflammation. Patients will be then classified for TR as responders if all individual lesions improved and non-responders if any of the lesions worsened, a new lesion developed at the 4 month MRE and all other scenarios not meeting definition of response. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vedolizumab 300 MG Injection [Entyvio] Vedolizumab will be initiated at 300 mg intravenous (IV) dosing at 0, 2 and 6 weeks followed by the 1st maintenance with 300 mg IV at week 14. Patients who have not achieved clinical response at week 14 will be eligible to undergo dose escalation to 4 weekly dosing of vedolizumab depending on the judgement of the treating gastroenterologist.
Vedolizumab 300 MG Injection \[Entyvio\]: Vedolizumab Injection | 48 |
| Total | 48 |
Baseline characteristics
| Characteristic | Vedolizumab 300 MG Injection [Entyvio] |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 48 Participants |
| Age, Continuous | 33.95 years |
| Baseline Crohn's Disease Activity Index Score | 143.00 units on a scale |
| Baseline EQ-5D Base_Anxiety 1 - Not anxious or depressed | 22 Participants |
| Baseline EQ-5D Base_Anxiety 2 - Slightly anxious or depressed | 6 Participants |
| Baseline EQ-5D Base_Anxiety 3 - Moderately anxious or depressed | 6 Participants |
| Baseline EQ-5D Base_Anxiety 4 - Severely anxious or depressed | 7 Participants |
| Baseline EQ-5D Base_Anxiety 5 - Extremely anxious or depressed | 0 Participants |
| Baseline EQ-5D Base_Anxiety NA | 7 Participants |
| Baseline EQ-5D Base_Mobility 1 - No problem walking | 36 Participants |
| Baseline EQ-5D Base_Mobility 2 - Slight problems walking | 2 Participants |
| Baseline EQ-5D Base_Mobility 3 - Moderate problems walking | 3 Participants |
| Baseline EQ-5D Base_Mobility 4 - Severe problems walking | 0 Participants |
| Baseline EQ-5D Base_Mobility 5 - Unable to walk | 0 Participants |
| Baseline EQ-5D Base_Mobility NA | 7 Participants |
| Baseline EQ-5D Base_Pain Discomfort 1 - No pain or discomfort | 15 Participants |
| Baseline EQ-5D Base_Pain Discomfort 2 - Slight pain or discomfort | 8 Participants |
| Baseline EQ-5D Base_Pain Discomfort 3 - Moderate pain or discomfort | 10 Participants |
| Baseline EQ-5D Base_Pain Discomfort 4 - Severe pain or discomfort | 6 Participants |
| Baseline EQ-5D Base_Pain Discomfort 5 - Extreme pain or discomfort | 2 Participants |
| Baseline EQ-5D Base_Pain Discomfort NA | 7 Participants |
| Baseline EQ-5D Base_Self-Care 1 - No problems washing or dressing | 37 Participants |
| Baseline EQ-5D Base_Self-Care 2 - Slight problems washing or dressing | 3 Participants |
| Baseline EQ-5D Base_Self-Care 3 - Moderate problems washing or dressing | 1 Participants |
| Baseline EQ-5D Base_Self-Care 4 - Severe problems washing or dressing | 0 Participants |
| Baseline EQ-5D Base_Self-Care 5 - Unable to wash or dress | 0 Participants |
| Baseline EQ-5D Base_Self-Care NA | 7 Participants |
| Baselin eEQ-5D Base_Usual Activities 1 - No problems doing usual activities | 26 Participants |
| Baselin eEQ-5D Base_Usual Activities 2 - Slight problems doing usual activities | 7 Participants |
| Baselin eEQ-5D Base_Usual Activities 3 - Moderate problems doing usual activities | 7 Participants |
| Baselin eEQ-5D Base_Usual Activities 4 - Severe problems doing usual activities | 1 Participants |
| Baselin eEQ-5D Base_Usual Activities 5 - Unable to do usual activities | 0 Participants |
| Baselin eEQ-5D Base_Usual Activities NA | 7 Participants |
| Baseline EQ-5D Base_Your Health Today, 0-100 | 80 units on a scale of 0-100 |
| Baseline Harvey Bradshaw Index Score | 5 units on a scale |
| BMI | 28.10 kg/m^2 |
| Montreal Age Classification 1 - Age of diagnosis at 16 years or younger | 6 Participants |
| Montreal Age Classification 2 - Age of diagnosis at 17-40 years | 32 Participants |
| Montreal Age Classification 3 - Age of diagnosis at >40 years | 10 Participants |
| Montreal Behavior B1 non-stricturing, non-penetrating | 22 Participants |
| Montreal Behavior B1p non-stricturing, non-penetrating with perianal disease | 3 Participants |
| Montreal Behavior B2p stricturing with perianal disease | 1 Participants |
| Montreal Behavior B2 stricturing | 8 Participants |
| Montreal Behavior B3 penetrating | 7 Participants |
| Montreal Behavior B3p penetrating with perianal disease | 7 Participants |
| Montreal Location L1 - terminal ileum | 8 participants |
| Montreal Location L3 - ileocolonic | 40 participants |
| Perianal Involvement No | 37 Participants |
| Perianal Involvement Perianal Involvement | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 38 Participants |
| Region of Enrollment United States | 48 participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 22 Participants |
| Upper GI Involvement No | 37 Participants |
| Upper GI Involvement Yes | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 2 |
| other Total, other adverse events | 0 / 46 | 0 / 2 |
| serious Total, serious adverse events | 0 / 46 | 0 / 2 |
Outcome results
Primary
Radiological Response
Radiological Transmural Response will be defined per-lesion and per-patient. Per-lesion TR will be defined as a decrease in the length of inflamed small bowel lesion from baseline or improvement in any imaging findings associated with severe mural inflammation, i.e., restricted diffusion, mural thickness, intramural T2 hyperintensity, peri-enteric T2 signal, and luminal ulcerations, without development of a new penetrating or stricturing complication. Worsened lesions will be fined as those with an increased score of any imaging parameter associated with severe mural inflammation. Unchanged lesions will be defined as those with unchanged (without worsening or improving) inflammatory parameters associated with severe mural inflammation. Patients will be then classified for TR as responders if all individual lesions improved and non-responders if any of the lesions worsened, a new lesion developed at the 4 month MRE and all other scenarios not meeting definition of response.
Time frame: 24±2 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vedolizumab 300 MG Injection [Entyvio] | Radiological Response | Transmural Ulcer Healing | 21 participants |
| Vedolizumab 300 MG Injection [Entyvio] | Radiological Response | Transmural Remission | 16 participants |
Primary
Radiological Response
Radiological Transmural Response will be defined per-lesion and per-patient. Per-lesion TR will be defined as a decrease in the length of inflamed small bowel lesion from baseline or improvement in any imaging findings associated with severe mural inflammation, i.e., restricted diffusion, mural thickness, intramural T2 hyperintensity, peri-enteric T2 signal, and luminal ulcerations, without development of a new penetrating or stricturing complication. Worsened lesions will be fined as those with an increased score of any imaging parameter associated with severe mural inflammation. Unchanged lesions will be defined as those with unchanged (without worsening or improving) inflammatory parameters associated with severe mural inflammation. Patients will be then classified for TR as responders if all individual lesions improved and non-responders if any of the lesions worsened, a new lesion developed at the 4 month MRE and all other scenarios not meeting definition of response.
Time frame: 52±2 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vedolizumab 300 MG Injection [Entyvio] | Radiological Response | Transmural Ulcer Healing | 12 participants |
| Vedolizumab 300 MG Injection [Entyvio] | Radiological Response | Transmural Remission | 9 participants |