Vedolizumab + Upadacitinib for Crohn's Disease
(VICTRIVA Trial)
Recruiting in Palo Alto (17 mi)
+8 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Takeda
Disqualifiers: Ulcerative colitis, Active infection, Herpes, others
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should have had an inadequate response to, loss of response to, or intolerance to corticosteroids, immunomodulators, or biologic therapy, which might imply changes to current treatments.
What data supports the effectiveness of the drugs Vedolizumab and Upadacitinib for Crohn's Disease?
Vedolizumab has been shown to be effective for Crohn's disease in patients who did not respond to other treatments, and Upadacitinib has demonstrated positive results in clinical trials and real-world settings, showing improvement in patients with moderate-to-severe Crohn's disease.
12345What safety data exists for Vedolizumab and Upadacitinib in humans?
Upadacitinib was found to be well-tolerated over 30 months in patients with Crohn's disease. Vedolizumab has been associated with some adverse events, including serious ones, but is generally considered safe for Crohn's disease and ulcerative colitis, with longer-term studies needed to fully understand its safety profile.
56789How is the drug combination of Vedolizumab and Upadacitinib unique for treating Crohn's Disease?
This treatment is unique because it combines Vedolizumab, a biologic drug that targets specific proteins involved in gut inflammation, with Upadacitinib, an oral medication that inhibits Janus kinase (JAK), a protein involved in immune response. This combination may offer a novel approach by targeting different pathways in the immune system compared to other treatments.
13101112Eligibility Criteria
Adults with moderately to severely active Crohn's Disease who haven't responded well to or can't tolerate corticosteroids, immunomodulators, or biologics. They must have a confirmed diagnosis for at least 3 months and show bowel inflammation on specific tests.Inclusion Criteria
I was diagnosed with Crohn's disease over 3 months ago, confirmed by tests and a biopsy.
My Crohn's disease is moderate to severe, with a CDAI score between 220-450.
My test shows significant inflammation in my intestines.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Induction
Participants receive vedolizumab and upadacitinib or vedolizumab and placebo for 12 weeks
12 weeks
4 visits (in-person)
Maintenance
Participants who respond to induction treatment receive vedolizumab monotherapy for 40 weeks
40 weeks
5 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
18 weeks
Participant Groups
The trial is testing if combining Vedolizumab and Upadacitinib (dual therapy) is better than using Vedolizumab alone (monotherapy) in reducing bowel inflammation after 12 weeks. Participants will first receive dual therapy, then responders continue with monotherapy for an additional 40 weeks.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: Main Study Maintenance Phase: Vedolizumab MonotherapyExperimental Treatment1 Intervention
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.
Group II: Double-blind Induction Phase: Vedolizumab + UpadacitinibExperimental Treatment2 Interventions
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.
Group III: Double-blind Induction Phase: Vedolizumab + PlaceboPlacebo Group2 Interventions
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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Peak Gastroenterology AssociatesColorado Springs, CO
GI PROS ResearchNaples, FL
Lenox Hill Hospital-Northwell HealthNew York, NY
Gastroenterology AssociatesGreenville, SC
More Trial Locations
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Who Is Running the Clinical Trial?
TakedaLead Sponsor
References
Multicentre Real-world Experience of Upadacitinib in the Treatment of Crohn's Disease. [2023]Upadacitinib is a selective Janus kinase inhibitor approved for the management of ulcerative colitis and is under evaluation for the management of Crohn's disease [CD] in Phase 3 clinical trials.
One-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multicentre cohort study. [2022]We recently showed that vedolizumab is effective in patients with Crohn's disease (CD) and ulcerative colitis (UC) with prior anti-TNF failure in a multicentre compassionate early-access programme before marketing authorisation was granted to vedolizumab.
Real-World Outcomes of Vedolizumab Therapy in Ulcerative Colitis and Crohn's Disease at a Tertiary Referral Center. [2018]Vedolizumab was approved for the therapy of ulcerative colitis and Crohn's disease in mid-2014. Real-world treatment data are necessary for a balanced assessment of its position among other therapeutic options.
Upadacitinib Is Safe and Effective for Crohn's Disease: Real-World Data from a Tertiary Center. [2023]Upadacitinib is a selective JAK-1 inhibitor approved for the treatment of rheumatoid arthritis and more recently, ulcerative colitis. Phase II trials demonstrated that upadacitinib induces endoscopic remission in patients with moderate-to-severe Crohn's disease. However, real-world data are lacking. We present a short report on our experience with off-label upadacitinib in patients with CD at a tertiary center. In this cohort of medically refractory patients with CD, treatment with upadacitinib resulted in subjective and objective responses in 25 and 42% of patients, respectively. Even at doses that are considered lower than currently being studied for CD, upadacitinib was associated with a favorable benefit-to-risk profile.
Upadacitinib Was Efficacious and Well-tolerated Over 30 Months in Patients With Crohn's Disease in the CELEST Extension Study. [2022]The long-term efficacy and safety of upadacitinib was evaluated in an open-label extension (OLE) of a phase II, double-blind, randomized trial of patients with Crohn's disease.
Retrospective Analysis of Safety of Vedolizumab in Patients With Inflammatory Bowel Diseases. [2021]There are few real-world data on the safety of vedolizumab for treatment of Crohn's disease (CD) or ulcerative colitis (UC). We quantified rates and identified factors significantly associated with infectious and non-infectious adverse events in clinical practice.
Vedolizumab as the first line of biologic therapy for ulcerative colitis and Crohn's disease - a systematic review with meta-analysis. [2023]The efficacy and safety of vedolizumab in bio-naïve patients with ulcerative colitis (UC) and Crohn's disease (CD) remain unknown.
Vedolizumab as Induction and Maintenance for Inflammatory Bowel Disease: 12-month Effectiveness and Safety. [2020]Vedolizumab is approved for moderate to severe Crohn's disease (CD) and ulcerative colitis (UC). We present prospective, 1-year data of the real-world effectiveness and safety of vedolizumab in inflammatory bowel disease.
Assessment of the real-world safety profile of vedolizumab using the United States Food and Drug Administration adverse event reporting system. [2023]Vedolizumab is the first gut-selective integrin blocker indicated for patients with Crohn's disease (CD) and ulcerative colitis (UC). This study aimed to examine the adverse events (AEs) profile of vedolizumab compared to anti-tumor necrosis factors (anti-TNFs) indicated for CD and UC using the FDA Adverse Event Reporting System (FAERS) database. AE reports with vedolizumab (5/20/2014-6/30/2015) and CD/UC-indicated anti-TNF drugs (adalimumab, infliximab, certolizumab pegol, and golimumab, during 8/1/1998-6/30/2015) as primary suspects were extracted from the FAERS database. AEs associated with vedolizumab were compared for signals of disproportionate reporting against anti-TNF drugs and all other drugs (1969-6/30/2015), using the proportional reporting ratio (PRR) and the empirical Bayesian geometric mean (EBGM) algorithms. The search retrieved 499 reports for vedolizumab and 119,620 reports for anti-TNFs, with 35.9% and 32.1% of these, respectively, being serious AEs. With the PRR approach, vedolizumab-associated reports had signals for 22 groups of AEs (9 were associated with serious outcomes) relative to anti-TNFs and had 34 signals relative to all other drugs. Signals detected included those reported as warnings in prescribing information and new AEs related to cardiovascular disease. Due to the voluntary nature of FAERS, this finding should be considered hypothesis generating (rather than hypothesis testing). Longer-term observational studies are required to evaluate the safety of vedolizumab.
Budget Impact of Adding Vedolizumab to a Health Plan Formulary as Another First-Line Biologic Option for Ulcerative Colitis and Crohn's Disease. [2022]Vedolizumab is a biologic drug approved by the US Food and Drug Administration (FDA) for the treatment of adults with moderately to severely active Crohn's disease (CD) or ulcerative colitis (UC) who have had inadequate response to, lost response to, or were intolerant of immunomodulators or tumor necrosis factor (TNF) blocker therapy, or who had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroid therapy. The biologics approved by the FDA for CD and/or UC include adalimumab, infliximab, golimumab, certolizumab, and ustekinumab.
Upadacitinib Induction and Maintenance Therapy for Crohn's Disease. [2023]Upadacitinib, an oral selective Janus kinase (JAK) inhibitor, is under investigation for the treatment of Crohn's disease.
Higher Trough Vedolizumab Concentrations During Maintenance Therapy are Associated With Corticosteroid-Free Remission in Inflammatory Bowel Disease. [2020]Vedolizumab is an anti-α4β7 biologic approved for ulcerative colitis [UC] and Crohn's disease [CD]. We aimed to examine the association of maintenance vedolizumab concentrations with remission.