Vedolizumab + Adalimumab/Ustekinumab for Crohn's Disease

Recruiting at 60 trial locations

Overseen By Sarah Glover

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Takeda

Must not be taking: Anti-integrin antibodies

Disqualifiers: Ulcerative colitis, Abdominal abscess, Tuberculosis, Hepatitis B, 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

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a combination of medications for individuals with moderate to severe Crohn's disease, which causes inflammation in the digestive tract. Participants will initially receive a mix of vedolizumab (Entyvio) with either adalimumab (Humira) or ustekinumab (Stelara) to determine if these combinations can manage symptoms. Those who benefit will then continue with vedolizumab alone to maintain improvement. Ideal participants are those who have tried other treatments for Crohn's but found them ineffective or intolerable. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, with research helping to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for these treatments?

Research has shown that vedolizumab, adalimumab, and ustekinumab are generally safe for treating Crohn's Disease. Vedolizumab has demonstrated a strong safety record across various studies, with some patients experiencing minor reactions at the injection site. Long-term use of vedolizumab has been positive for many patients, with few serious side effects reported.

When combined with adalimumab, studies indicate that this treatment is effective and maintains a good safety record. Some patients have reported mild side effects, which are usually easy to manage.

Similarly, combining vedolizumab with ustekinumab yields similar safety results. Research indicates both drugs generally have a low rate of serious side effects. Ustekinumab users reported a few adverse events, but these were not significantly different from those seen with vedolizumab.

Overall, these treatments are well-tolerated by most patients, with a low chance of serious side effects. Participants in clinical trials often report minor and manageable side effects, reflecting the treatments' established safety profiles. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for Crohn's Disease, which often rely on single biologic agents, the investigational approach of combining Vedolizumab with either Adalimumab or Ustekinumab offers a novel synergy. Vedolizumab specifically targets the gut, potentially minimizing systemic side effects, while Adalimumab and Ustekinumab work through different immune pathways, offering a multi-faceted attack on inflammation. This combination therapy could provide enhanced efficacy for patients who do not respond adequately to conventional single-agent therapies. Researchers are hopeful that this dual-targeted approach will lead to better disease control and improved quality of life for patients.

What evidence suggests that this trial's treatments could be effective for Crohn's Disease?

Research shows that vedolizumab effectively treats Crohn's disease. One study found that 48% of people taking vedolizumab were symptom-free after one year. In this trial, participants in Part A, Cohort 1 will receive a combination of vedolizumab and adalimumab, which previous studies have shown resulted in 54.5% of patients being symptom-free after 26 weeks. Meanwhile, participants in Part A, Cohort 2 will receive a combination of vedolizumab and ustekinumab, which also seems promising for people with more difficult cases of Crohn's disease. These findings suggest that these treatments can help manage symptoms and improve the quality of life for those with moderate to severe Crohn's disease. ^{4 6 7 8 9}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

Adults with moderate to severe Crohn's Disease who have had an inadequate response, lost response, or intolerance to certain treatments. They must have a confirmed diagnosis for at least 3 months and meet specific disease severity scores. Not eligible if they've had extensive colon resections, certain infections like TB or HIV, previous nonresponse to multiple treatments, or any immunodeficiency.

Inclusion Criteria

I was diagnosed with Crohn's disease over 3 months ago, confirmed by an endoscopy.

My Crohn's disease is active, with a high severity score.

I am in remission at 26 weeks or showing significant improvement.

Exclusion Criteria

I have been diagnosed with ulcerative colitis or indeterminate colitis.

I have a perianal fistula with an abscess.

I had major surgery on my colon with at least 2 parts left, over 6 months ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive dual targeted treatment with vedolizumab and either adalimumab or ustekinumab

26 weeks

Multiple visits for IV and SC administration

Treatment Part B

Participants who achieve clinical remission in Part A receive vedolizumab monotherapy

16 weeks

IV administration 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

• Adalimumab
• Ustekinumab
• Vedolizumab

Trial Overview

The trial is testing the effectiveness of vedolizumab IV in combination with either adalimumab or ustekinumab in treating Crohn's Disease. Participants first receive dual therapy (Part A), then those responding continue with only vedolizumab (Part B). The follow-up period lasts at least 26 weeks post-treatment.

How Is the Trial Designed?

Group I: Part B: Vedolizumab Monotherapy Experimental Treatment 1 Intervention

Participants who achieve therapeutic benefit in Part A will receive vedolizumab IV 300 mg monotherapy, Q8W from Week 30 until Week 46 and will be followed up to Week 52.

Group II: Part A, Cohort 2: Vedolizumab + Ustekinumab Experimental Treatment 2 Interventions

Participants will receive vedolizumab IV 300 mg, at Weeks 0, 2, and 6, then Q8W until Week 22 and ustekinumab IV 520, 390, or 260 mg (weight-based), then SC 90 mg 8 weeks after initial IV dose, then Q8W until Week 24.

Group III: Part A, Cohort 1: Vedolizumab + Adalimumab Experimental Treatment 2 Interventions

Participants will receive vedolizumab IV 300 mg, at Weeks 0, 2, and 6, then every 8 weeks (Q8W) until Week 22 and adalimumab SC 160, 80, and 40 mg at Weeks 0, 2, and 4, respectively, then 40 mg every 2 weeks (Q2W) until Week 26.

Adalimumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Approved in United States as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis
• Hidradenitis suppurativa

Approved in Canada as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Approved in Japan as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

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 study of 536 patients with Crohn's disease, ustekinumab demonstrated significantly higher rates of clinical remission, steroid-free remission, and objective response compared to vedolizumab at both 26 and 52 weeks, indicating its greater effectiveness as a treatment.

Both ustekinumab and vedolizumab had similar rates of adverse events, suggesting that ustekinumab's superior efficacy does not come at the cost of increased safety risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of ustekinumab vs. vedolizumab for anti-TNF-naïve or anti-TNF-exposed Crohn's disease: a multicenter cohort study. Yang, H., Huang, Z., Li, M., et al.[2023]

In a phase 3b trial involving 386 biologic-naive patients with moderately to severely active Crohn's disease, both ustekinumab and adalimumab were found to be highly effective, with similar rates of clinical remission at week 52 (65% for ustekinumab vs. 61% for adalimumab).

Safety profiles for both treatments were consistent with previous studies, with low rates of serious infections (2% for ustekinumab and 3% for adalimumab) and no reported deaths during the study period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn's disease: a multicentre, randomised, double-blind, parallel-group, phase 3b trial. Sands, BE., Irving, PM., Hoops, T., et al.[2022]

A study involving 117 Crohn's disease patients, including 39 elderly (≥65 years) and 78 nonelderly (<65 years), found that ustekinumab (UST) is safe and effective for treating elderly patients, with nearly 90% experiencing a clinical response.

Elderly patients were less likely to achieve complete clinical remission compared to nonelderly patients (28.2% vs. 52.6%), but there were no significant differences in adverse events or complications between the two age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness and Safety of Ustekinumab in Elderly Crohn's Disease Patients. Garg, R., Aggarwal, M., Butler, R., et al.[2023]

In a study of 100 patients with Crohn's disease who failed anti-TNF and either vedolizumab or ustekinumab, 30.7% achieved clinical remission after receiving a third-line treatment by week 48.

The study found that 76.5% of patients remained surgery-free at 48 weeks, with ileal disease localization being a significant risk factor for needing surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The outcome of Crohn's disease patients refractory to anti-TNF and either vedolizumab or ustekinumab. Kassouri, L., Amiot, A., Kirchgesner, J., et al.[2021]

In a study of 470 patients with Crohn's disease who had previously failed TNF inhibitors, vedolizumab showed significantly higher rates of clinical remission (55.5%) and steroid-free remission (51.1%) compared to ustekinumab (42.5% and 40.6%, respectively) at 52 weeks.

Both treatments demonstrated similar safety profiles and initial clinical effectiveness at 26 weeks, but vedolizumab was more effective in achieving long-term remission by the end of the year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Objective Comparison of Vedolizumab and Ustekinumab Effectiveness in Crohn's Disease Patients' Failure to TNF-Alpha Inhibitors. Onali, S., Pugliese, D., Caprioli, FA., et al.[2022]

In a meta-analysis of five high-quality studies involving 1026 patients with Crohn's disease who were refractory to anti-TNF therapy, ustekinumab and vedolizumab showed similar effectiveness in achieving clinical remission at week 14.

However, at week 52, ustekinumab demonstrated significantly higher rates of clinical remission, steroid-free clinical remission, biological remission, and treatment persistence compared to vedolizumab, indicating it may be a more effective long-term maintenance treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review with meta-analysis: the effectiveness of either ustekinumab or vedolizumab in patients with Crohn's disease refractory to anti-tumour necrosis factor. Parrot, L., Dong, C., Carbonnel, F., et al.[2022]

In a study of 1,375 patients with Crohn's disease who had previously been treated with anti-TNF therapy, both ustekinumab and vedolizumab showed similar rates of treatment persistence beyond 52 weeks.

However, ustekinumab was associated with significantly lower rates of all-cause hospitalization, nonsurgical CD hospitalizations, and hospitalizations for infection, suggesting it may be a safer option for patients switching therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Evidence Comparing Vedolizumab and Ustekinumab in Antitumor Necrosis Factor-Experienced Patients With Crohn's Disease. Kappelman, MD., Adimadhyam, S., Hou, L., et al.[2023]

In a systematic review of five randomized controlled trials involving patients with moderate-to-severe Crohn's disease who were nonresponsive or intolerant to TNF-antagonist therapy, ustekinumab and vedolizumab showed no significant differences in clinical response or remission during both induction and maintenance phases.

The safety profiles of ustekinumab and vedolizumab were also comparable, with no significant differences in the risk of adverse events, indicating that both treatments are similarly safe for patients with Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An indirect comparison of ustekinumab and vedolizumab in the therapy of TNF-failure Crohn's disease patients. Kawalec, P., Moćko, P.[2019]

In a 52-week study involving 24 patients with Crohn's disease who previously lost response to infliximab, adalimumab demonstrated significant efficacy, with clinical remission rates increasing from 35% at baseline to 58% at week 52.

Adalimumab was well tolerated, with no patients experiencing intolerance and no serious toxicities reported, indicating it is a safe option for maintaining remission in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab maintenance therapy for Crohn's disease with intolerance or lost response to infliximab: an open-label study. Peyrin-Biroulet, L., Laclotte, C., Bigard, MA.[2015]

In a study of 213 Crohn's disease patients who failed anti-TNF treatment, ustekinumab was found to be more effective than vedolizumab in achieving corticosteroid-free clinical remission and biochemical remission after 52 weeks of treatment.

Both treatments had comparable safety outcomes, indicating that while ustekinumab may offer better efficacy, it does not pose a higher risk of adverse events compared to vedolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab is associated with superior effectiveness outcomes compared to vedolizumab in Crohn's disease patients with prior failure to anti-TNF treatment. Biemans, VBC., van der Woude, CJ., Dijkstra, G., et al.[2021]

In a study of adult patients with Crohn's disease initiating biologic treatment, ustekinumab was found to significantly lower the risk of serious infections compared to TNF-α antagonists and vedolizumab, indicating it may be a safer option for these patients.

Despite the differences in infection risk, ustekinumab did not show any significant differences in hospitalization or surgery rates compared to the other treatments, suggesting its effectiveness in managing Crohn's disease is comparable to TNF-α antagonists and vedolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Safety and Effectiveness of Biologic Therapy for Crohn's Disease: A CA-IBD Cohort Study. Singh, S., Kim, J., Luo, J., et al.[2023]

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