Vedolizumab + Tofacitinib for Ulcerative Colitis

Recruiting in Palo Alto (17 mi)

+51 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Takeda

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

Disqualifiers: Active infection, Tuberculosis, Hepatitis, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The main aim of this study is to learn about the effect of treatment with vedolizumab IV (vedolizumab) together with tofacitinib in adults with moderate and severe ulcerative colitis (UC). Another aim is to learn about treatment with Vedolizumab alone after the double treatment. All participants will receive vedolizumab together with tofacitinib for 8 weeks and will be checked for response. Participants who show a response to the treatment after 8 weeks will be treated with vedolizumab alone for an additional 44 weeks. Each participant will be followed up for at least 26 weeks after the last dose of vedolizumab.

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 data supports the effectiveness of the drug Tofacitinib for treating ulcerative colitis?

Research shows that Tofacitinib, an oral drug, is effective in helping patients with moderate-to-severe ulcerative colitis achieve and maintain remission (a period without symptoms). Studies have demonstrated its safety and effectiveness in real-world settings and clinical trials. ^{1 2 3 4 5}

Is the combination of Vedolizumab and Tofacitinib safe for treating ulcerative colitis?

Tofacitinib, used for ulcerative colitis, has been studied for safety, showing a similar rate of serious adverse events compared to other treatments, with no major differences in risks like blood clots or heart issues. However, there is a noted risk of herpes zoster (shingles) and some differences in safety profiles across populations. ^{6 7 8 9 10}

How is the drug combination of Vedolizumab and Tofacitinib unique for treating ulcerative colitis?

This treatment combines Vedolizumab, a biologic that targets the gut specifically, with Tofacitinib, an oral medication that inhibits Janus kinase (a protein involved in inflammation). This combination may offer a novel approach for patients who have not responded well to other treatments, like anti-TNF drugs. ^{8 11 12 13 14}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Tofacitinib (Other)
• Vedolizumab (Monoclonal Antibodies)

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.

Participant Groups

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.

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 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 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 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]

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 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 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 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]

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 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 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Real-world evidence of tofacitinib effectiveness and safety in patients with refractory ulcerative colitis. [2021]

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

Real-world clinical and endoscopic outcomes after one year tofacitinib treatment in ulcerative colitis. [2023]

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

Real-World Experience with Tofacitinib in IBD at a Tertiary Center. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Predictors of Sustained Response With Tofacitinib Therapy in Patients With Ulcerative Colitis. [2023]

5. Australia pubmed.ncbi.nlm.nih.gov

Safety and efficacy of long-term tofacitinib treatment in East Asian patients with ulcerative colitis in OCTAVE Open. [2022]

6. Korea (South) 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. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Profile of Tofacitinib in the Treatment of Ulcerative Colitis: An Evidence-Based Review of Recent Data. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Tofacitinib as Induction and Maintenance Therapy in Japanese Patients with Active Ulcerative Colitis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Tofacitinib Response in Ulcerative Colitis (TOUR): Early Response After Initiation of Tofacitinib Therapy in a Real-world Setting. [2023]

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

Safety of Tofacitinib in a Real-World Cohort of Patients With Ulcerative Colitis. [2022]

11. England 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. [2023]

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

Longitudinal monitoring of STAT3 phosphorylation and histologic outcome of tofacitinib therapy in patients with ulcerative colitis. [2022]

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

Efficacy and Safety of Tofacitinib in Ulcerative Colitis Based on Prior Tumor Necrosis Factor Inhibitor Failure Status. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Real-world Evidence Comparing Tofacitinib and Vedolizumab in Anti-TNF-experienced Patients With Ulcerative Colitis. [2023]