Crohn's Disease
Conditions
Keywords
Drug Therapy
Brief summary
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.
Detailed description
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.
Interventions
DRUGVedolizumab
Vedolizumab IV infusion.
DRUGUpadacitinib
Upadacitinib over-encapsulated tablets.
DRUGPlacebo
Upadacitinib matched placebo capsules.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. The participant has a diagnosis of CD established at least 3 months before screening by clinical and endoscopic evidence and corroborated by a histopathology report. 2. The participant has a confirmed diagnosis of moderately to severely active CD as assessed by CDAI of 220-450. 3. The participant has evidence of mucosal inflammation based on the SES-CD: SES-CD score of \>=6 (or \>=4 for participants with isolated ileal disease), as confirmed by a central reader. 4. The participant has demonstrated an inadequate response to, loss of response to, or intolerance to corticosteroids, immunomodulators, or biologic therapy.
Exclusion criteria
1. The participant has a current diagnosis of ulcerative colitis or indeterminate colitis. 2. The participant has infection(s) requiring treatment with IV anti-infectives within 30 days prior to baseline or oral/intramuscular anti-infectives within 14 days prior to baseline. 3. The participant has evidence of an active infection during the screening period, or clinically significant infection within 30 days prior to screening, or ongoing chronic infection. 4. The participant has a history of recurrent or disseminated (including a single episode) herpes zoster, or disseminated (including a single episode) herpes simplex. 5. The participant has any of the following ongoing known complications of CD: abscess (abdominal or peri-anal); symptomatic bowel strictures; 2 entire missing segments of the following 5 segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum; fulminant colitis; toxic megacolon; or any other manifestation that might require surgery while enrolled in the study. 6. The participant has an ostomy or ileoanal pouch. 7. The participant has severe renal impairment, defined as an estimated glomerular filtration rate of \<30 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2). 8. The participant has severe (Child-Pugh C) hepatic impairment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Clinical Remission Based on the CDAI at Week 12 | Week 12 | Clinical remission is defined as a CDAI score of less than (\<) 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. |
| Percentage of Participants Exhibiting an Endoscopic Response Based on Simple Endoscopic Score for CD (SES-CD) at Week 12 | Week 12 | Endoscopic response per SES-CD is defined as decrease in SES CD greater than (\>) 50% from baseline (or for participants with isolated ileal disease, SES-CD \<=4 or a \>=2-point reduction in SES-CD 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving 2-item Patient-reported Outcome Measure (PRO2) Based Clinical Remission at Week 12 | Week 12 | Clinical remission based on PRO2 is defined as 7-day average of very soft or liquid stool frequency (SF) less than or equal to ( \<=) 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. |
| Percentage of Participants Achieving Endoscopic Remission Based on SES-CD at Week 12 | Week 12 | Endoscopic remission as per SES-CD is defined as a SES-CD score of \<=4 and no subscore \>1, read centrally. 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. |
| Percentage of Participants Exhibiting Corticosteroid-free Clinical Remission in Participants who Were Taking Corticosteroids at Baseline Based on the CDAI at Week 12 | 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. 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. |
| Percentage of Participants Exhibiting a Clinical Response Based on the CDAI at Week 12 | 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. |
| Percentage of Participants Achieving Clinical Remission Based on the CDAI at Week 52 | 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. |
| Percentage of Participants Exhibiting an Endoscopic Response Based on SES-CD at Week 52 | Week 52 | Endoscopic response per SES-CD is defined as a decrease in SES CD \>50% from baseline (or for participants with isolated ileal disease,SES-CD \<=4 or a \>=2-point reduction in SES-CD 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. |
| Percentage of Participants Achieving 2-item PRO2 Based Clinical Remission at Week 52 | 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. |
| Percentage of Participants Achieving Endoscopic Remission Based on SES-CD at Week 52 | Week 52 | Endoscopic remission as per SES-CD is defined as a SES-CD score of \<=4 and no subscore \>1, read centrally . 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. |
| Percentage of Participants Exhibiting Corticosteroid-free Clinical Remission in Participants who Were Taking Corticosteroids at Baseline Based on the CDAI at Week 52 | 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. 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 |
| Percentage of Participants Exhibiting a Clinical Response Based on the CDAI at Week 52 | 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. |
Countries
Austria, Belgium, Brazil, Canada, Croatia, Czechia, Denmark, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Netherlands, Norway, Poland, Portugal, Slovenia, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
CONTACTTakeda Contact
STUDY_DIRECTORStudy Director
Takeda
Outcome results
None listed