Crohn's Disease
Vedolizumab With or Without Upadacitinib for Active Crohn’s Disease
This study asks whether combining vedolizumab with upadacitinib during 12 weeks of induction reduces Crohn’s disease activity and bowel inflammation more than vedolizumab with placebo in adults with moderately to severely active disease.
Registry title: A Study of Vedolizumab With and Without Upadacitinib in Adults With Crohn's Disease
9 recruiting U.S. sites ↓Study at a glance
- Age
- 18 Years–65 Years
- Treatment
- Vedolizumab or Upadacitinib
- Design
- Randomized · Quadruple
- Central study contact
- Takeda Contact+1-877-825-3327medinfoUS@takeda.com
- Sponsor
- Takeda
Research question
Among adults with moderately to severely active Crohn’s disease, how do 12 weeks of vedolizumab plus upadacitinib compare with vedolizumab plus placebo for clinical remission, endoscopic response, and safety?
Participant snapshot
Who the study is looking for
- The study is looking for adults ages 18 through 65 with Crohn’s disease.
- The Crohn’s disease diagnosis must have been established at least three months before screening using clinical and endoscopic evidence supported by a pathology report.
- The study is looking for moderately to severely active disease, including a Crohn’s Disease Activity Index score of 220 to 450 and specified endoscopic evidence of inflammation.
- Participants must have had an inadequate response, loss of response, or intolerance to corticosteroids, immunomodulators, or biologic therapy.
Participation overview
What participation may involve
Participation lasts approximately 70 weeks: a 12-week induction phase, a 40-week vedolizumab maintenance phase for participants meeting the Week 12 response threshold, and an 18-week safety follow-up. What participation may involve: - During induction, participants receive 300 mg of intravenous vedolizumab at Weeks 0, 2, 6, and 10. - During induction, participants take either 45 mg of upadacitinib or matched placebo by mouth once daily for 12 weeks. - Participants with at least a 70-point reduction in Crohn’s Disease Activity Index score at Week 12 enter maintenance and receive vedolizumab alone from Week 14 through Week 52. - Maintenance vedolizumab is scheduled every eight weeks and may be increased to every four weeks at the investigator’s discretion. - Clinical symptoms, bowel inflammation, endoscopic findings, and safety are assessed during the study. The registry reports an overall participation time of approximately 70 weeks. The registry reports 15 study-clinic visits.
Study interventions
What participants may receive or do
- Vedolizumab: Vedolizumab is given by intravenous infusion in both induction groups and as monotherapy during maintenance for participants who meet the Week 12 response threshold.
- Upadacitinib: Upadacitinib is supplied as over-encapsulated tablets and taken by mouth once daily with vedolizumab during the 12-week induction phase.
- Placebo: The placebo consists of capsules matched to upadacitinib and is taken by mouth once daily with vedolizumab during the 12-week induction phase.
Study design
How the comparison works
This Phase 3, multicenter treatment study has a blinded 12-week induction comparison followed by vedolizumab-only maintenance for participants who meet the specified Week 12 response threshold and an additional safety follow-up period. Participants are randomly assigned in a 1:1 ratio to one of two induction groups: vedolizumab plus upadacitinib or vedolizumab plus placebo. During the blinded comparison, participants, care providers, investigators, and outcome assessors are masked to induction assignment. The control group receives the same vedolizumab infusion schedule as the combination group but takes matched oral placebo instead of upadacitinib during induction. Induction assignment is 1:1 between two groups, one of which receives upadacitinib-matched placebo with vedolizumab for 12 weeks.
Reported activities
Procedures and tests
- Vedolizumab is administered through intravenous infusions.
- Upadacitinib or matched placebo is taken by mouth once daily during induction.
- The Crohn’s Disease Activity Index is used to assess symptoms and clinical response or remission.
- Ileocolonoscopy findings are scored with the Simple Endoscopic Score for Crohn’s Disease and read centrally for endoscopic outcomes.
- A two-item patient-reported outcome uses seven-day averages of stool frequency and abdominal pain.
- Screening must confirm the Crohn’s disease diagnosis through clinical and endoscopic evidence supported by a histopathology report.
- Screening must confirm the required Crohn’s Disease Activity Index range and endoscopic inflammation score.
- Kidney function is relevant because severe renal impairment is an exclusion criterion based on estimated glomerular filtration rate.
- Liver function is relevant because severe Child-Pugh C hepatic impairment is an exclusion criterion.
Eligibility highlights
Details that may affect whether you contact the study
These are selected highlights, not a complete eligibility check. Exact criteria remain in the full registry record below.
Common requirements
- Crohn’s disease must have been diagnosed at least three months before screening using clinical and endoscopic evidence supported by a pathology report.
- Disease activity must be moderate to severe, with a Crohn’s Disease Activity Index score from 220 through 450.
- A central reader must confirm a Simple Endoscopic Score for Crohn’s Disease of at least 6, or at least 4 for isolated ileal disease.
- There must have been an inadequate response, loss of response, or intolerance to corticosteroids, immunomodulators, or biologic therapy.
Possible reasons someone may not be able to join
- A current diagnosis of ulcerative colitis or indeterminate colitis is excluded.
- An infection treated with intravenous anti-infective medication within 30 days before baseline, or oral or intramuscular anti-infective medication within 14 days before baseline, is excluded.
- Active infection during screening, clinically significant infection within 30 days before screening, or an ongoing chronic infection is excluded.
- A history of recurrent or disseminated herpes zoster, or disseminated herpes simplex, is excluded as specified by the registry.
- Certain ongoing Crohn’s disease complications are excluded, including abscess, symptomatic stricture, specified missing bowel segments, fulminant colitis, toxic megacolon, or another manifestation that might require surgery during the study.
- People with an ostomy or ileoanal pouch are excluded.
- Severe kidney impairment, defined as an estimated glomerular filtration rate below 30 mL/min/1.73 m², is excluded.
- Severe liver impairment classified as Child-Pugh C is excluded.
Important unknowns
What the record does not make clear
- The registry reports 15 clinic visits and provides treatment timing, but it does not give a complete visit-by-visit schedule.
- The record discusses prior treatment response and outcomes involving baseline corticosteroid use but does not clearly state which current Crohn’s disease medicines may continue.
- The record does not provide washout requirements for prior Crohn’s disease treatments.
- The record does not describe rescue treatment if Crohn’s disease worsens or does not respond.
- The registry requires endoscopic evidence at screening and reports endoscopic outcomes at Weeks 12 and 52, but it does not provide a complete procedure and preparation schedule.
- The record does not state which study-related or routine-care costs are covered or billed to insurance.
- The record does not state whether participants receive compensation or expense reimbursement.
- The record does not describe transportation, lodging, or other travel assistance.
- The record does not say whether any visits or assessments may be completed remotely.
- The record does not describe access to study treatment after participation ends.
- The study is listed as recruiting overall, but individual locations have recruiting, not-yet-recruiting, and active-not-recruiting statuses.
- Only participants reaching the specified Week 12 response threshold enter the main maintenance phase, but the record does not explain what study care follows for those who do not reach it.
Before contacting the site
Questions for the study team
- What happens at each of the 15 clinic visits, and how long should I expect each visit to take?
- Which current Crohn’s disease medicines may continue, and are there required washout periods?
- How many ileocolonoscopies are required, and what preparation, sedation, and recovery time are involved?
- What care or treatment is offered if I do not reach the Week 12 response threshold or if my Crohn’s disease worsens?
- Which study-related costs are covered, and are compensation, travel reimbursement, or lodging assistance available?
- Is the site I would contact currently screening participants, and can any study activities be completed remotely or near home?
Before changing care
Questions for your gastroenterologist
- How might screening or participation affect the Crohn’s disease medicines I currently take?
- How stable is my Crohn’s disease now, and what concerns would you have about the study’s induction and maintenance plan in my clinical situation?
- What approved treatment alternatives should I understand while considering whether to contact the study team?
- If I contact the study team, how should your office and the research team coordinate medication decisions, infection monitoring, endoscopy results, and care for a flare?
This plain-language digest is provided by the Aidy clinical trials API. It may omit details and is not medical advice or an eligibility decision. Review the full registry record and confirm details with the study team.
Source record
Full registry record
The sections below preserve the study information supplied through ClinicalTrials.gov, including complete descriptions, criteria, outcomes, and locations.
About this study
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 design and administration
- Organization
- Takeda
- Organization class
- Industry
- Organization study ID
- Vedolizumab-3043
- Lead sponsor
- Takeda
- Sponsor class
- Industry
- Enrollment type
- Estimated
- Allocation
- Randomized
- Intervention model
- Sequential
- Primary purpose
- Treatment
- Masking
- Quadruple
- Who is masked
- Participant, Care Provider, Investigator, Outcomes Assessor
- Standard age groups
- Adult, Older Adult
Study arms
Experimental
Double-blind Induction Phase: Vedolizumab + 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.
Interventions: Drug: Vedolizumab, Drug: Upadacitinib
Placebo Comparator
Double-blind Induction Phase: Vedolizumab + 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.
Interventions: Drug: Vedolizumab, Drug: Placebo
Experimental
Main Study Maintenance Phase: Vedolizumab Monotherapy
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.
Interventions: Drug: Vedolizumab
Interventions
Drug
Vedolizumab
Vedolizumab IV infusion.
Drug
Upadacitinib
Upadacitinib over-encapsulated tablets.
Drug
Placebo
Upadacitinib matched placebo capsules.
Eligibility
18 Years–65 Years
All
Not accepted
Inclusion criteria (4)
- 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.Registry-derived · unreviewed
- The participant has a confirmed diagnosis of moderately to severely active CD as assessed by CDAI of 220-450.Registry-derived · unreviewed
- 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.Registry-derived · unreviewed
- The participant has demonstrated an inadequate response to, loss of response to, or intolerance to corticosteroids, immunomodulators, or biologic therapy.Registry-derived · unreviewed
Exclusion criteria (8)
- The participant has a current diagnosis of ulcerative colitis or indeterminate colitis.Registry-derived · unreviewed
- 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.Registry-derived · unreviewed
- 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.Registry-derived · unreviewed
- The participant has a history of recurrent or disseminated (including a single episode) herpes zoster, or disseminated (including a single episode) herpes simplex.Registry-derived · unreviewed
- 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.Registry-derived · unreviewed
- The participant has an ostomy or ileoanal pouch.Registry-derived · unreviewed
- 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).Registry-derived · unreviewed
- The participant has severe (Child-Pugh C) hepatic impairment.Registry-derived · unreviewed
This information can identify a possible match, conflict, or item needing confirmation. Only the study team can determine eligibility.
Study outcomes
Primary outcome
Percentage of Participants Achieving Clinical Remission Based on the CDAI at Week 12
Time frame: 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.
Primary outcome
Percentage of Participants Exhibiting an Endoscopic Response Based on Simple Endoscopic Score for CD (SES-CD) at Week 12
Time frame: 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 outcome
Percentage of Participants Achieving 2-item Patient-reported Outcome Measure (PRO2) Based Clinical Remission at Week 12
Time frame: 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.
Secondary outcome
Percentage of Participants Achieving Endoscopic Remission Based on SES-CD at Week 12
Time frame: 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.
Secondary outcome
Percentage of Participants Exhibiting Corticosteroid-free Clinical Remission in Participants who Were Taking Corticosteroids at Baseline Based on the CDAI at Week 12
Time frame: 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.
Secondary outcome
Percentage of Participants Exhibiting a Clinical Response Based on the CDAI at Week 12
Time frame: 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.
Secondary outcome
Percentage of Participants Achieving Clinical Remission Based on the CDAI at Week 52
Time frame: 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.
Secondary outcome
Percentage of Participants Exhibiting an Endoscopic Response Based on SES-CD at Week 52
Time frame: 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.
Secondary outcome
Percentage of Participants Achieving 2-item PRO2 Based Clinical Remission at Week 52
Time frame: 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.
Secondary outcome
Percentage of Participants Achieving Endoscopic Remission Based on SES-CD at Week 52
Time frame: 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.
Secondary outcome
Percentage of Participants Exhibiting Corticosteroid-free Clinical Remission in Participants who Were Taking Corticosteroids at Baseline Based on the CDAI at Week 52
Time frame: 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
Secondary outcome
Percentage of Participants Exhibiting a Clinical Response Based on the CDAI at Week 52
Time frame: 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.
Recruiting locations in the United States
UCSD Medical Center
Not Yet RecruitingLa Jolla, California, 92037, United States
Site Contact858-246-2544sis040@health.ucsd.edu
Siddharth Singh
Keck Medicine Of USC - USC Healthcare Center 1
Not Yet RecruitingLos Angeles, California, 90033, United States
Site Contact888-700-5700sarah.sheibani@med.usc.edu
Sarah Sheibani
Peak Gastroenterology Associates
RecruitingColorado Springs, Colorado, 80907, United States
Site Contact719-310-6719bpatel@peakgastro.com
Bhaktasharan Patel
Columbia University Medical Center, New York-Presbyterian Hospital
Not Yet RecruitingNew York, New York, 10032, United States
Site Contact212-305-9664bs3270@cumc.columbia.edu
Bo Shen
Southern Star Research Institute, LLC
RecruitingSan Antonio, Texas, 78229, United States
Site Contact210-581-2812js_bull@yahoo.com
Jeff Bullock
Tyler Research Institute, LLC
RecruitingTyler, Texas, 75701, United States
Site Contact903-630-6211aarond@tylerri.com
George Duvall
Swedish Cancer Institute
Not Yet RecruitingSeattle, Washington, 98104, United States
Site Contact206-215-4250michael.chiorean@swedish.org
Michael Chiorean
University of Washington Medical Center - Montlake
Not Yet RecruitingSeattle, Washington, 98195, United States
Site Contact206-543-3500scottl@medicine.washington.edu
Scott Lee
Medical College of Wisconsin Cancer Center - Froedtert Hospital
Not Yet RecruitingMilwaukee, Wisconsin, 53226, United States
Site Contact414-955-6827pbeniwal@mcw.edu
Poonam Beniwal-Patel
This study also lists 119 locations outside the United States. They are not shown here.
Central study contacts
Registry dates
- First posted
- Jan 29, 2024
- Primary completion
- Jun 8, 2027
- Overall completion
- Aug 1, 2028
Trial information comes from ClinicalTrials.gov and may change. Confirm current status, eligibility, and site details with the study team. Aidy does not provide medical advice or determine eligibility.