The main aim of this study is to learn whether vedolizumab and upadacitinib given together (also called dual targeted therapy or DTT) reduces bowel inflammation and ulcers in the bowel compared to vedolizumab only (also called monotherapy) in adults with moderately or severely active Crohn's Disease (CD) after 12 weeks of treatment. Other aims are to learn how safe and effective DTT is compared to monotherapy for these participants. All participants will receive DTT (either vedolizumab and upadacitinib or vedolizumab and placebo) for 12 weeks. Participants responding to the treatment will then receive vedolizumab only (monotherapy) for an additional 40 weeks. During the study, participants will visit their study clinic 15 times.
The drug being tested in this study is vedolizumab. Vedolizumab is being tested to treat people with moderately to severely active CD. The study will look at the efficacy and safety of vedolizumab with and without upadacitinib. The study will enroll approximately 396 patients. Participants will be assigned in a 1:1 ratio to one of the two treatment groups in the 12-weeks Induction Phase: * Induction Phase: Vedolizumab + Upadacitinib * Induction Phase: Vedolizumab + Placebo Participants who achieve a Crohn's disease activity index (CDAI) reduction of greater than or equal to (\>=)70 points from baseline at Week 12 will enter the main study Maintenance Phase (40 weeks) of the study to receive vedolizumab monotherapy. Participants will be followed for a further 18-week safety follow-up period up to Week 70. This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 70 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
396
Vedolizumab IV infusion.
Upadacitinib over-encapsulated tablets.
Upadacitinib matched placebo capsules.
UCSD Medical Center
La Jolla, California, United States
NOT_YET_RECRUITINGKeck Medicine Of USC - USC Healthcare Center 1
Los Angeles, California, United States
NOT_YET_RECRUITINGPeak Gastroenterology Associates
Colorado Springs, Colorado, United States
RECRUITINGGI PROS, Inc.
Naples, Florida, United States
Percentage of Participants Achieving Clinical Remission Based on the CDAI at Week 12
Clinical remission is defined as a CDAI score of \<150 points. CDAI assesses CD based on clinical signs such as number of liquid or very soft stools, abdominal pain, general wellbeing, extra-intestinal manifestations of CD, antidiarrheal use, presence of abdominal mass, hematocrit, and body weight. 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 12
Percentage of Participants Exhibiting an Endoscopic Response Based on Simple Endoscopic Score for CD (SES-CD) at Week 12
Endoscopic response per SES-CD is assessed as proportion of participants achieving decrease in SES CD \>50% from baseline (for participants with isolated ileal disease,SES-CD \<=4 or \<=2-point reduction from baseline) read centrally. SES-CD evaluates 4 endoscopic variables (ulcer size,percentage of ulcerated and affected surface area,presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy (ileum,right,transverse,and left colon,rectum). Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is most severe case, with sum of the scores for each variable ranging from 0 to 15, except for presence of narrowing. Presence of narrowing ranges from 0 to 11 since a severity of 3 represents a narrowing which a colonoscope cannot be passed and, thus, can only be observed once among the bowel segments. Overall SES-CD score ranges from 0 to 56 and is sum of 4 variables across 5 bowel segments. Higher scores indicate more severe disease.
Time frame: Week 12
Percentage of Participants Achieving 2-item Patient-reported Outcome Measure (PRO2) Based Clinical Remission at Week 12
Clinical remission based on PRO2 is defined as 7-day average of very soft or liquid stool frequency (SF) \<=2.8, 7-day average of abdominal pain (AP) score \<=1.0, and neither worse than baseline. The PRO2 is comprised of the stool frequency and abdominal pain components of the CDAI.
Time frame: Week 12
Percentage of Participants Achieving Endoscopic Remission Based on SES-CD at Week 12
Endoscopic remission as per SES-CD is defined as an SES-CD score of ≤4 with no mucosal ulceration in the colon or ileum as assessed by centrally read video ileocolonoscopy. SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of surface area (SA) that is ulcerated, percentage of SA affected, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy. Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is most severe case, with sum of scores for each variable ranging from 0 to 15, except for presence of narrowing. Presence of narrowing ranges from 0 to 11 since a severity of 3 represents a narrowing which a colonoscope cannot be passed and, thus, can only be observed once among the bowel segments. The overall SES-CD score ranges from 0 to 56 and is sum of 4 variables across 5 bowel segments. Higher scores indicate more severe disease.
Time frame: Week 12
Percentage of Participants Exhibiting Corticosteroid-free Clinical Remission in Participants who Were Taking Corticosteroids at Baseline Based on the CDAI at Week 12
Percentage of participants using oral corticosteroids at Baseline who have discontinued corticosteroids and are in clinical remission per CDAI at Week 12 will be reported. Clinical remission is defined as a CDAI score of \<150 points. CDAI assesses CD based on clinical signs such as number of liquid or very soft stools, abdominal pain, general wellbeing, extra-intestinal manifestations of CD, antidiarrheal use, presence of abdominal mass, hematocrit, and body weight. CDAI consist 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 12
Percentage of Participants Exhibiting a Clinical Response Based on the CDAI at Week 12
Clinical response is defined as \>=100-point decrease from Baseline in CDAI score. CDAI assesses CD based on clinical signs such as number of liquid or very soft stools, abdominal pain, general wellbeing, extra-intestinal manifestations of CD, antidiarrheal use, presence of abdominal mass, hematocrit, and body weight. CDAI consist 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 12
Percentage of Participants Achieving Clinical Remission Based on the CDAI at Week 52
Clinical remission is defined as a CDAI score of \<150 points. CDAI assesses CD based on clinical signs such as number of liquid or very soft stools, abdominal pain, general wellbeing, extra-intestinal manifestations of CD, antidiarrheal use, presence of abdominal mass, hematocrit, and body weight. 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 52
Percentage of Participants Exhibiting an Endoscopic Response Based on SES-CD at Week 52
Endoscopic response per SES-CD is assessed as proportion of participants achieving decrease in SES CD \>50% from baseline (for participants with isolated ileal disease,SES-CD \<=4 or \<=2-point reduction from baseline) read centrally. SES-CD evaluates 4 endoscopic variables (ulcer size,percentage of ulcerated and affected surface area,presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy (ileum,right,transverse,and left colon,and rectum). Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is most severe case, with sum of scores for each variable ranging from 0 to 15, except for presence of narrowing. Presence of narrowing ranges from 0 to 11 since a severity of 3 represents a narrowing which a colonoscope cannot be passed and, thus, can only be observed once among the bowel segments. Overall SES-CD score ranges from 0 to 56 and is sum of 4 variables across 5 bowel segments. Higher scores indicate more severe disease.
Time frame: Week 52
Percentage of Participants Achieving 2-item PRO2 Based Clinical Remission at Week 52
Clinical remission based on PRO2 is defined as 7-day average of very soft or liquid stool frequency (SF) \<=2.8, 7-day average of abdominal pain (AP) score \<=1.0, and neither worse than baseline. The PRO2 is comprised of the stool frequency and abdominal pain components of the CDAI.
Time frame: Week 52
Percentage of Participants Achieving Endoscopic Remission Based on SES-CD at Week 52
Endoscopic remission as per SES-CD is defined as an SES-CD score of \<=4 with no mucosal ulceration in the colon or ileum as assessed by centrally read video ileocolonoscopy. SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of surface area (SA) that is ulcerated, percentage of SA affected, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy. Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is most severe case, with sum of scores for each variable ranging from 0 to 15, except for presence of narrowing. Presence of narrowing ranges from 0 to 11 since a severity of 3 represents a narrowing which a colonoscope cannot be passed and, thus, can only be observed once among the bowel segments. The overall SES-CD score ranges from 0 to 56 and is sum of 4 variables across 5 bowel segments. Higher scores indicate more severe disease.
Time frame: Week 52
Percentage of Participants Exhibiting Corticosteroid-free Clinical Remission in Participants who Were Taking Corticosteroids at Baseline Based on the CDAI at Week 52
Percentage of participants using oral corticosteroids at Baseline who have discontinued corticosteroids and are in clinical remission at Week 52 per CDAI will be reported. Clinical remission is defined as a CDAI score of \<150 points. CDAI assesses CD based on clinical signs such as number of liquid or very soft stools, abdominal pain, general wellbeing, extra-intestinal manifestations of CD, antidiarrheal use, presence of abdominal mass, hematocrit, and body weight. CDAI consist 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 52
Percentage of Participants Exhibiting a Clinical Response Based on the CDAI at Week 52
Clinical response is defined as \>=100-point decrease from Baseline in CDAI score. CDAI assesses CD based on clinical signs such as number of liquid or very soft stools, abdominal pain, general wellbeing, extra-intestinal manifestations of CD, antidiarrheal use, presence of abdominal mass, hematocrit, and body weight. CDAI consist 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 52
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Orlando Health Ambulatory Care Center
Orlando, Florida, United States
ACTIVE_NOT_RECRUITINGUSF Health Morsani Center for Advanced Healthcare
Tampa, Florida, United States
ACTIVE_NOT_RECRUITINGIndiana University (IU) Health University Hospital
Indianapolis, Indiana, United States
ACTIVE_NOT_RECRUITINGUniversity of Kentucky
Lexington, Kentucky, United States
ACTIVE_NOT_RECRUITINGMount Sinai Hospital - The Susan and Leonard Feinstein Inflammatory Bowel Disease (IBD) Clinical Center
New York, New York, United States
ACTIVE_NOT_RECRUITINGColumbia University Medical Center, New York-Presbyterian Hospital
New York, New York, United States
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