A Study of Vedolizumab With and Without Upadacitinib in Adults With Crohn's Disease
- Conditions
- Crohn's Disease
- Interventions
- Registration Number
- NCT06227910
- Lead Sponsor
- Takeda
- 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-week Induction Period:
* Induction Period: Vedolizumab + Upadacitinib
* Induction Period: Vedolizumab + Placebo
Participants who achieve a Crohn's disease activity index (CDAI) reduction of ≥70 points from baseline at Week 12 will progress into the 40-week Maintenance Period 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 396
- 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.
- The participant has a confirmed diagnosis of moderately to severely active CD as assessed by CDAI of 220-450.
- The participant has evidence of mucosal inflammation based on the SES-CD: SES-CD score (excluding the presence of narrowing component) of ≥6 (or ≥4 for participants with isolated ileal disease), as confirmed by a central reader.
- The participant has demonstrated an inadequate response to, loss of response to, or intolerance to corticosteroids, immunomodulators, or biologic therapy.
- The participant has a current diagnosis of ulcerative colitis or indeterminate colitis.
- The participant has previously failed >2 classes of either biological or small molecule therapy for CD.
- 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.
- 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.
- The participant has a history of recurrent or disseminated (including a single episode) herpes zoster, or disseminated (including a single episode) herpes simplex.
- 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.
- The participant has an ostomy or ileoanal pouch.
- 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).
- The participant has severe (Child-Pugh C) hepatic impairment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Double-blind Induction Phase: Vedolizumab + Upadacitinib Vedolizumab Participants will receive vedolizumab 300 mg intravenous (IV) infusion at Weeks 0, 2, 6 and 10 along with upadacitinib 45 mg, orally, once daily (QD) for 12 weeks. Double-blind Induction Phase: Vedolizumab + Upadacitinib Upadacitinib Participants will receive vedolizumab 300 mg intravenous (IV) infusion at Weeks 0, 2, 6 and 10 along with upadacitinib 45 mg, orally, once daily (QD) for 12 weeks. Double-blind Induction Phase: Vedolizumab + Placebo Vedolizumab Participants will receive vedolizumab IV 300 mg infusion, at Weeks 0, 2, 6 and 10 along with upadacitinib matched placebo, orally, QD for 12 weeks. Double-blind Induction Phase: Vedolizumab + Placebo Placebo Participants will receive vedolizumab IV 300 mg infusion, at Weeks 0, 2, 6 and 10 along with upadacitinib matched placebo, orally, QD for 12 weeks. Main Study Maintenance Phase: Vedolizumab Monotherapy Vedolizumab Participants who achieve a CDAI reduction of \>=70 points from baseline at Week 12 will receive vedolizumab 300 mg IV infusion (monotherapy), every 8 weeks (Q8W) starting at Week 14 to 52. The Q8W vedolizumab monotherapy may be escalated to Q4W at the investigator's discretion.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Clinical Remission Based on the CDAI at Week 12 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.
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 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.
- Secondary Outcome Measures
Name Time Method 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) \<=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 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.
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. 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.
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 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.
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 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.
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. 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.
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.
Trial Locations
- Locations (138)
UCSD Medical Center
🇺🇸La Jolla, California, United States
Keck Medicine Of USC - USC Healthcare Center 1
🇺🇸Los Angeles, California, United States
Peak Gastroenterology Associates
🇺🇸Colorado Springs, Colorado, United States
GI PROS, Inc.
🇺🇸Naples, Florida, United States
Orlando Health Ambulatory Care Center
🇺🇸Orlando, Florida, United States
USF Health Morsani Center for Advanced Healthcare
🇺🇸Tampa, Florida, United States
Indiana University (IU) Health University Hospital
🇺🇸Indianapolis, Indiana, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Mount Sinai Hospital - The Susan and Leonard Feinstein Inflammatory Bowel Disease (IBD) Clinical Center
🇺🇸New York, New York, United States
Columbia University Medical Center, New York-Presbyterian Hospital
🇺🇸New York, New York, United States
Scroll for more (128 remaining)UCSD Medical Center🇺🇸La Jolla, California, United StatesSite ContactContact858-246-2544sis040@health.ucsd.eduSiddharth SinghPrincipal Investigator