Vedolizumab + Tofacitinib for Ulcerative Colitis

Recruiting at 56 trial locations

Overseen By Takeda Contact

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Takeda

Must not be taking: Immunomodulators, Immunosuppressants, NSAIDs, others

Disqualifiers: Active infection, Tuberculosis, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 8

Duration: 8 weeks

65 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining vedolizumab (a gut-selective integrin antagonist) and tofacitinib (a Janus kinase inhibitor) for individuals with moderate to severe ulcerative colitis, a condition that causes inflammation and sores in the colon. Participants will initially receive both treatments for 8 weeks to assess symptom improvement. Those who respond well will then continue with only vedolizumab for an additional 44 weeks. Suitable candidates for this trial include individuals who have had ulcerative colitis for at least 3 months and have not responded well to other similar treatments. As a Phase 4 trial, this study involves treatments that are already FDA-approved and proven effective, aiming to understand how they benefit more patients.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting. You must stop immunomodulators 4 weeks before, immunosuppressants 8 weeks before, and any medicines affecting CYP3A4 enzymes 2 weeks before joining the study. If you're on corticosteroids, you need to be on a stable dose and follow a tapering plan.

What is the safety track record for these treatments?

Research shows that using tofacitinib and vedolizumab together is safe for treating ulcerative colitis, especially in patients who have already tried anti-TNF therapies. Studies have found that patients generally tolerate this combination well, with safety similar to other treatments used when initial options fail.

These studies report that patients did not experience unusual or severe side effects during treatment. More than half of the patients responded well, indicating that the combination is effective and safe for many. While all treatments carry potential risks, evidence supports the overall safety of using these two drugs together. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the combination of Vedolizumab and Tofacitinib for treating ulcerative colitis because it brings together two unique mechanisms of action. Vedolizumab is an integrin antagonist that targets the gut specifically, potentially reducing side effects compared to broad-acting immunosuppressants. Tofacitinib, on the other hand, is a JAK inhibitor that works by interfering with the signaling pathways that drive inflammation. This combination could offer a more comprehensive approach to managing inflammation with the potential for faster symptom relief compared to standard treatments like corticosteroids or other biologics.

What evidence suggests that this trial's treatments could be effective for ulcerative colitis?

Research has shown that both vedolizumab and tofacitinib effectively treat ulcerative colitis (UC), but they function differently. Tofacitinib proved more effective than vedolizumab for patients who previously tried other anti-TNF treatments. However, in everyday use, both treatments have demonstrated similar results in improving symptoms and healing the gut. For patients who haven't used biologic treatments before, vedolizumab tends to last longer as a treatment option. In this trial, participants will receive a combination of vedolizumab and tofacitinib, which might offer a comprehensive approach by addressing UC from different angles, potentially benefiting patients with moderate to severe UC. ^{2 4 5 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

Adults with moderate to severe ulcerative colitis (UC) diagnosed at least 3 months ago, who haven't responded well or are intolerant to up to two TNF antagonists. They should have UC extending beyond the rectum and be current on colorectal cancer screenings if at risk. Participants can't join if they've had major colon surgery, certain infections like hepatitis B/C or TB, recent heart issues, or a history of lymphoproliferative disease.

Inclusion Criteria

I have tried up to 2 TNF blockers without success or could not tolerate them.

My ulcerative colitis affects more than 15 cm of my colon.

I was diagnosed with ulcerative colitis over 3 months ago, confirmed by tests and a biopsy.

Exclusion Criteria

A positive test for hepatitis B virus (HBV).

I have not had a Clostridium difficile infection or treatment for any intestinal pathogen in the last 28 days.

I have complications related to ulcerative colitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vedolizumab IV and tofacitinib for 8 weeks to assess response

8 weeks

Vedolizumab IV at Week 0, 2, and 6; Tofacitinib orally twice daily

Monotherapy

Participants with clinical response transition to vedolizumab monotherapy

44 weeks

Vedolizumab IV every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

26 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tofacitinib
• Vedolizumab

Trial Overview The trial is testing vedolizumab IV in combination with tofacitinib for adults with UC for the first 8 weeks. Those responding will continue vedolizumab alone for another 44 weeks. The study aims to understand the effects of this combined treatment followed by monotherapy with vedolizumab.

How Is the Trial Designed?

Group I: Vedolizumab 300 mg + Tofacitinib 10 mg Experimental Treatment 2 Interventions

Participants will receive Vedolizumab 300 mg, intravenous (IV) infusion, at Week 0, Week 2 and Week 6 along with Tofacitinib 10 mg, tablets, orally, twice daily from Week 0 to Week 8. Participants with clinical response at Week 8 will transition to receive vedolizumab 300 mg IV infusion every 8 weeks (Q8W) through Week 46.

Tofacitinib is already approved in United States, European Union for the following indications:

Approved in United States as Xeljanz for:

• Rheumatoid Arthritis
• Psoriatic Arthritis
• Ulcerative Colitis
• Ankylosing Spondylitis
• Polyarticular Course Juvenile Idiopathic Arthritis

Approved in European Union as Xeljanz for:

• Rheumatoid Arthritis
• Psoriatic Arthritis
• Ulcerative Colitis
• Ankylosing Spondylitis

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

Published Research Related to This Trial

In a long-term study of 105 East Asian patients with ulcerative colitis, tofacitinib demonstrated significant efficacy, with 68.2% of patients on 5 mg and 54.2% on 10 mg experiencing clinical response after 36 months.

While the incidence rate of herpes zoster was higher in East Asian patients compared to the global population, overall safety and efficacy profiles of tofacitinib were consistent with those observed in the broader study population, with no deaths or major adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of long-term tofacitinib treatment in East Asian patients with ulcerative colitis in OCTAVE Open. Matsuoka, K., Hisamatsu, T., Kim, HJ., et al.[2022]

In a study of 59 patients with highly refractory ulcerative colitis, tofacitinib demonstrated the ability to induce endoscopic improvement in 30.5% of patients after 48 weeks, indicating its efficacy in this challenging population.

Endoscopic improvement at week 8 was linked to a higher likelihood of continuing treatment long-term, suggesting that early response may predict better adherence to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal monitoring of STAT3 phosphorylation and histologic outcome of tofacitinib therapy in patients with ulcerative colitis. Verstockt, B., Volk, V., Jaeckel, C., et al.[2022]

Tofacitinib showed greater efficacy in achieving remission in Japanese patients with moderate-to-severe ulcerative colitis, with 22.4% of patients in the OCTAVE Induction 1 study achieving remission compared to 7.7% in the placebo group.

The safety profile of tofacitinib in Japanese patients was consistent with that of the global population, with no new or unexpected safety risks identified, indicating it is a safe treatment option for this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib as Induction and Maintenance Therapy in Japanese Patients with Active Ulcerative Colitis. Suzuki, Y., Watanabe, M., Matsui, T., et al.[2022]

In a study of 736 ulcerative colitis patients who had previously used anti-TNF inhibitors, those starting treatment with tofacitinib showed lower treatment persistence over 52 weeks compared to those starting vedolizumab, with an adjusted risk ratio of 0.77.

No significant differences were found in secondary safety and effectiveness outcomes, such as hospitalization rates for infections or other complications, between the two treatment groups, suggesting similar safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world Evidence Comparing Tofacitinib and Vedolizumab in Anti-TNF-experienced Patients With Ulcerative Colitis. Adimadhyam, S., Lewis, JD., Simon, AL., et al.[2023]

In a study of 36 patients with moderate to severe ulcerative colitis treated with tofacitinib for up to one year, 39% achieved combined steroid-free clinical remission and endoscopic improvement, indicating its efficacy in a real-world setting.

The study also found that 33% of patients permanently withdrew from tofacitinib treatment, primarily due to infections, highlighting the importance of monitoring safety and drug survival, which was 60% at one year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world clinical and endoscopic outcomes after one year tofacitinib treatment in ulcerative colitis. Straatmijer, T., van Gennep, S., Duijvestein, M., et al.[2023]

In a study of 58 patients with moderate-to-severe inflammatory bowel disease (IBD) who were resistant to anti-TNF therapy, tofacitinib led to a clinical response in 69% of patients, demonstrating its efficacy as a treatment option.

By 12 months of treatment, 27% of patients achieved clinical, steroid-free remission, indicating that tofacitinib can provide significant long-term benefits for patients with difficult-to-treat IBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Experience with Tofacitinib in IBD at a Tertiary Center. Weisshof, R., Aharoni Golan, M., Sossenheimer, PH., et al.[2022]

In a study of 487 patients with ulcerative colitis, 34.9% achieved remission after 52 weeks of maintenance therapy with tofacitinib, indicating its effectiveness as a treatment option.

Baseline factors such as a lower endoscopic subscore, a partial Mayo score below 2, and younger age were associated with higher chances of achieving remission, while oral corticosteroid use and higher C-reactive protein levels were linked to lower chances of remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of Sustained Response With Tofacitinib Therapy in Patients With Ulcerative Colitis. Sandborn, WJ., Armuzzi, A., Liguori, G., et al.[2023]

In a real-world study of 260 ulcerative colitis patients treated with tofacitinib, adverse events (AEs) occurred in 15.7% of patients, with infections being the most common type.

Serious AEs, including herpes zoster (HZ) and venous thromboembolism (VTE), were reported, particularly in patients receiving a higher dose of 10 mg twice daily, suggesting that dose de-escalation may be beneficial to minimize risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Tofacitinib in a Real-World Cohort of Patients With Ulcerative Colitis. Deepak, P., Alayo, QA., Khatiwada, A., et al.[2022]

In a study of 38 patients with moderate-to-severe ulcerative colitis who were resistant to other treatments, 34% achieved steroid-free clinical remission after 48 weeks of treatment with tofacitinib, demonstrating its effectiveness in a challenging patient population.

The study also found that 70% of patients avoided colectomy (surgical removal of the colon) within a year, indicating that tofacitinib can help manage severe cases of ulcerative colitis with an acceptable safety profile, despite some patients experiencing adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world evidence of tofacitinib effectiveness and safety in patients with refractory ulcerative colitis. Lair-Mehiri, L., Stefanescu, C., Vaysse, T., et al.[2021]

Tofacitinib is effective in treating ulcerative colitis (UC) in patients regardless of whether they have previously failed treatment with tumor necrosis factor inhibitors (TNFi), based on data from over 1,100 participants in phase 3 studies.

However, patients with prior TNFi failure experienced higher rates of herpes zoster (HZ) infections when treated with tofacitinib, indicating a potential safety concern that needs to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tofacitinib in Ulcerative Colitis Based on Prior Tumor Necrosis Factor Inhibitor Failure Status. Sandborn, WJ., Peyrin-Biroulet, L., Sharara, AI., et al.[2022]

In a study of 1,026 patients with ulcerative colitis, tofacitinib showed a serious adverse event (SAE) incidence of 4.06 per 100 person-years, which is comparable to the 6.30 per 100 person-years in patients treated with anti-TNF inhibitors (TNFi).

No thromboembolic events were reported in the tofacitinib group, and the rates of herpes zoster and tuberculosis were similar between tofacitinib and TNFi groups, suggesting a favorable safety profile for tofacitinib in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Comparative Risk of Serious Adverse Events With Tofacitinib and TNF Inhibitors in Patients With Ulcerative Colitis: The Korean Experience as Revealed by a National Database. Seo, GH., Jung, SH.[2022]

Tofacitinib is a new oral medication that works by inhibiting Janus kinases, which are important in the inflammation process of ulcerative colitis (UC), and has been approved by the FDA and EMA for treating moderate-to-severe UC.

Clinical trials (Phase II and III) have shown that tofacitinib is effective in inducing and maintaining remission in UC, especially for patients who do not respond to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of Tofacitinib in the Treatment of Ulcerative Colitis: An Evidence-Based Review of Recent Data. Varyani, F., Argyriou, K., Phillips, F., et al.[2023]

In a real-world study of 96 patients with ulcerative colitis, tofacitinib showed significant and rapid improvement in disease activity starting as early as day 3, with a notable decline in the simple clinical colitis activity index (SCCAI).

The safety profile of tofacitinib was consistent with previous findings, with low rates of discontinuation due to adverse events, and 25% of patients achieving steroid-free remission by day 14.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib Response in Ulcerative Colitis (TOUR): Early Response After Initiation of Tofacitinib Therapy in a Real-world Setting. Long, MD., Afzali, A., Fischer, M., et al.[2023]

In a study of 304 patients with ulcerative colitis who had previously failed anti-TNF therapy, tofacitinib achieved higher rates of endoscopic improvement and histological healing compared to vedolizumab at week 16.

Tofacitinib was particularly more effective in patients with severe disease and those who had experienced primary failure to biologic treatments, suggesting it may be a better option for these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world comparison of effectiveness between tofacitinib and vedolizumab in patients with ulcerative colitis exposed to at least one anti-TNF agent. Buisson, A., Nachury, M., Guilmoteau, T., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35644343/

Superior Effectiveness of Tofacitinib Compared to ... Conclusions: Tofacitinib was associated with superior effectiveness outcomes compared with vedolizumab in anti-TNF-experienced patients with UC along with ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1590865825007352

Real-life effectiveness and safety of tofacitinib ... Clinical, biochemical, endoscopic, and histologic outcomes showed no difference between tofacitinib and vedolizumab at weeks 26 and 52.

3. academic.oup.com academic.oup.com/ecco-jcc/article/19/7/jjae188/7920833

Tofacitinib Versus Vedolizumab Among Bio-naive Patients ... The data presented here demonstrates that vedolizumab exhibits better persistence than tofacitinib among biologic-naive patients with over 70% ...

4. cghjournal.org cghjournal.org/article/S1542-3565(22)00510-9/fulltext

Superior Effectiveness of Tofacitinib Compared to ... Tofacitinib was associated with superior effectiveness outcomes compared with vedolizumab in anti-TNF experienced patients with UC along with ...

5. gastrojournal.org gastrojournal.org/article/S0016-5085(24)05480-5/fulltext

Comparative Efficacy of Advanced Therapies for ... With an estimated placebo rate of achieving remission of 5% in biologic-exposed patients with moderate-to-severe UC, we anticipate that 70%, 55% ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40335332/

A multicenter cohort IGIBD study (VE2TO-UC) Conclusions: Tofacitinib and vedolizumab were equally effective and safe as second-line therapy in anti-TNFs experienced UC patients.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40755085/

Efficacy and Safety of Vedolizumab and Tofacitinib (VETO) ... VETO was effective and safe in patients with UC refractory to anti-TNF and second-line therapies, with over half achieving clinical ...