Vedolizumab + Upadacitinib for Crohn's Disease

(VICTRIVA Trial)

Recruiting at 141 trial locations

Overseen By Matthew Barnes

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Takeda

Disqualifiers: Ulcerative colitis, Active infection, Herpes, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

396 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

What 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. ^{5 6 7 8 9}

How 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. ^{1 3 10 11 12}

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.

Research Team

Study Director

Principal Investigator

Takeda

Eligibility 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.

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

Treatment Details

Interventions

• Upadacitinib
• Vedolizumab

Trial Overview 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.

Participant Groups

Group I: Main Study Maintenance Phase: Vedolizumab Monotherapy Experimental Treatment 1 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 + Upadacitinib Experimental Treatment 2 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 + Placebo Placebo Group 2 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.

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Findings from Research

In a real-world study of 45 patients with moderate to severe Crohn's disease treated with upadacitinib, 63.6% achieved a clinical response and 27.2% achieved clinical remission after 3 months, indicating its efficacy in managing the disease.

The safety profile of upadacitinib was acceptable, with 26.7% of patients experiencing adverse events, and only 4.5% having serious adverse events without any reported mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicentre Real-world Experience of Upadacitinib in the Treatment of Crohn's Disease. Chugh, R., Braga-Neto, MB., Fredrick, TW., et al.[2023]

Vedolizumab demonstrated the ability to maintain steroid-free clinical remission in 27.2% of patients with Crohn's disease and 40.5% of patients with ulcerative colitis at week 54, indicating its efficacy in long-term treatment.

The safety profile of vedolizumab was reasonable, with no deaths reported and only 7.2% of patients experiencing severe adverse events, although a notable number of patients, especially those with Crohn's disease, experienced a loss of response during the first year of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multicentre cohort study. Amiot, A., Serrero, M., Peyrin-Biroulet, L., et al.[2022]

In a study of 53 patients with ulcerative colitis and Crohn's disease receiving vedolizumab therapy, 20% of ulcerative colitis patients and 14.3% of Crohn's disease patients achieved remission by week 30, indicating some efficacy in a treatment-refractory population.

Despite some patients responding to vedolizumab, a significant portion (48% for ulcerative colitis and 39.4% for Crohn's disease) did not respond satisfactorily, highlighting the need for alternative treatment options for those not achieving remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Outcomes of Vedolizumab Therapy in Ulcerative Colitis and Crohn's Disease at a Tertiary Referral Center. Hoffmann, P., Krisam, J., Stremmel, W., et al.[2018]

In a cohort of patients with medically refractory Crohn's disease, treatment with upadacitinib led to subjective responses in 25% and objective responses in 42% of patients, indicating its potential effectiveness in real-world settings.

Even at lower doses than those currently being studied, upadacitinib demonstrated a favorable benefit-to-risk profile, suggesting it may be a safe option for patients with Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib Is Safe and Effective for Crohn's Disease: Real-World Data from a Tertiary Center. Traboulsi, C., Ayoub, F., Silfen, A., et al.[2023]

In a long-term study of 107 patients with Crohn's disease, upadacitinib demonstrated sustained clinical remission rates of around 54-61% over 30 months, indicating its efficacy as a treatment.

While upadacitinib showed long-term benefits, the safety profile revealed that higher doses (30 mg) were associated with increased rates of adverse events compared to lower doses (15 mg), consistent with its known safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib Was Efficacious and Well-tolerated Over 30 Months in Patients With Crohn's Disease in the CELEST Extension Study. D'Haens, G., Panés, J., Louis, E., et al.[2022]

In a study of 1087 patients with Crohn's disease and ulcerative colitis, vedolizumab demonstrated a favorable safety profile, with a low overall infection rate of 6.3% and non-infectious adverse events primarily being arthralgias (2.9%).

Factors such as active smoking and the use of multiple immunosuppressive agents were found to significantly increase the risk of infections in patients receiving vedolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Analysis of Safety of Vedolizumab in Patients With Inflammatory Bowel Diseases. Meserve, J., Aniwan, S., Koliani-Pace, JL., et al.[2021]

Vedolizumab demonstrated significant efficacy in bio-naïve patients with ulcerative colitis (UC) and Crohn's disease (CD), with 63.9% of UC patients and 61.7% of CD patients achieving clinical remission by week 52.

Bio-naïve patients with UC experienced a lower risk of serious adverse events compared to those previously treated, indicating a favorable safety profile for vedolizumab in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab as the first line of biologic therapy for ulcerative colitis and Crohn's disease - a systematic review with meta-analysis. Attauabi, M., Madsen, GR., Bendtsen, F., et al.[2023]

In a real-world study of 132 patients with moderate to severe Crohn's disease (CD) and ulcerative colitis (UC), vedolizumab showed sustained clinical response, with 35% of UC patients and 31% of CD patients achieving steroid-free remission after 12 months.

Mucosal healing was observed in 52% of UC patients and 30% of CD patients, indicating that vedolizumab is effective in promoting healing in the intestines, with most adverse events being minor and 74% of patients continuing treatment after one year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab as Induction and Maintenance for Inflammatory Bowel Disease: 12-month Effectiveness and Safety. Christensen, B., Colman, RJ., Micic, D., et al.[2020]

Vedolizumab, a gut-selective integrin blocker for Crohn's disease and ulcerative colitis, showed a similar rate of serious adverse events (35.9%) compared to anti-TNF drugs (32.1%) in a study analyzing 499 reports for vedolizumab and 119,620 for anti-TNFs.

The study identified 22 groups of adverse events associated with vedolizumab, including 9 with serious outcomes, suggesting potential cardiovascular risks; however, these findings are preliminary and require further investigation through long-term studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the real-world safety profile of vedolizumab using the United States Food and Drug Administration adverse event reporting system. Cross, RK., Chiorean, M., Vekeman, F., et al.[2023]

Including vedolizumab as a preferred first-line biologic treatment for ulcerative colitis (UC) and Crohn's disease (CD) in a health plan formulary can lead to significant cost savings, ranging from $0.13 million to $1.63 million in the first year and up to $4.68 million by the third year.

The analysis suggests that using vedolizumab earlier in treatment, rather than as a second-line option, not only improves patient access to effective therapy but also reduces overall healthcare costs for the health plan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budget Impact of Adding Vedolizumab to a Health Plan Formulary as Another First-Line Biologic Option for Ulcerative Colitis and Crohn's Disease. Wilson, M., Lucas, A., Cameron, A., et al.[2022]

In two phase 3 trials involving over 1,500 patients with moderate-to-severe Crohn's disease, upadacitinib (45 mg) significantly improved clinical remission and endoscopic response compared to placebo after 12 weeks of treatment.

During the maintenance phase, both 15 mg and 30 mg doses of upadacitinib continued to show superior efficacy in maintaining clinical remission and endoscopic response over 52 weeks, although higher doses were associated with increased risks of herpes zoster infections and other adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib Induction and Maintenance Therapy for Crohn's Disease. Loftus, EV., Panés, J., Lacerda, AP., et al.[2023]

In a study of 258 inflammatory bowel disease patients on maintenance vedolizumab, those in clinical and biochemical remission had significantly higher drug concentrations (12.7 µg/mL) compared to those with active disease (10.1 µg/mL), indicating a strong association between higher vedolizumab levels and remission.

Patients with vedolizumab concentrations above 11.5 µg/mL were nearly 2.4 times more likely to achieve corticosteroid-free clinical and biochemical remission, suggesting that maintaining adequate drug levels is crucial for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher Trough Vedolizumab Concentrations During Maintenance Therapy are Associated With Corticosteroid-Free Remission in Inflammatory Bowel Disease. Ungaro, RC., Yarur, A., Jossen, J., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Multicentre Real-world Experience of Upadacitinib in the Treatment of Crohn's Disease. [2023]

2. England pubmed.ncbi.nlm.nih.gov

One-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multicentre cohort study. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Outcomes of Vedolizumab Therapy in Ulcerative Colitis and Crohn's Disease at a Tertiary Referral Center. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Upadacitinib Is Safe and Effective for Crohn's Disease: Real-World Data from a Tertiary Center. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Upadacitinib Was Efficacious and Well-tolerated Over 30 Months in Patients With Crohn's Disease in the CELEST Extension Study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Retrospective Analysis of Safety of Vedolizumab in Patients With Inflammatory Bowel Diseases. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Vedolizumab as the first line of biologic therapy for ulcerative colitis and Crohn's disease - a systematic review with meta-analysis. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Vedolizumab as Induction and Maintenance for Inflammatory Bowel Disease: 12-month Effectiveness and Safety. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Assessment of the real-world safety profile of vedolizumab using the United States Food and Drug Administration adverse event reporting system. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Budget Impact of Adding Vedolizumab to a Health Plan Formulary as Another First-Line Biologic Option for Ulcerative Colitis and Crohn's Disease. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Upadacitinib Induction and Maintenance Therapy for Crohn's Disease. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Higher Trough Vedolizumab Concentrations During Maintenance Therapy are Associated With Corticosteroid-Free Remission in Inflammatory Bowel Disease. [2020]