Vedolizumab + Adalimumab/Ustekinumab for Crohn's Disease

Recruiting at 57 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

150 Participants Needed

Trial Summary

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 data supports the effectiveness of the drug combination Vedolizumab + Adalimumab/Ustekinumab for Crohn's Disease?

Research shows that Adalimumab can help patients with Crohn's disease who did not respond well to another drug called infliximab. Additionally, Ustekinumab and Vedolizumab have been compared and used effectively in patients who did not respond to other treatments, suggesting they may be beneficial in combination. ^{1 2 3 4 5}

Is the combination of Vedolizumab, Adalimumab, and Ustekinumab safe for humans?

Research shows that Vedolizumab, Adalimumab, and Ustekinumab have been studied for safety in people with Crohn's disease. These studies generally indicate a favorable safety profile, meaning they are considered safe for use in humans, although specific safety data for the combination of all three is not detailed. ^{1 3 4 6 7}

How is the combination of Vedolizumab, Adalimumab, and Ustekinumab unique for treating Crohn's disease?

This treatment is unique because it combines three different drugs, each with a distinct mechanism of action, to target Crohn's disease. Vedolizumab works by blocking white blood cells from entering the gut, Adalimumab is an anti-TNF drug that reduces inflammation, and Ustekinumab targets specific proteins involved in inflammation. This combination may offer a new option for patients who have not responded to other treatments. ^{6 8 9 10 11}

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 adalimumab or vedolizumab together with ustekinumab in adults with moderate to severe Crohn's Disease, and the effect of treatment with vedolizumab alone, after the dual targeted treatment. The study is conducted in two parts. In Part A, participants will receive the dual targeted treatment (vedolizumab together with either adalimumab or ustekinumab). In part B, participants will receive vedolizumab only. Part B will include participants who responded to the treatment in Part A. Each participant will be followed up for at least 26 weeks after the last dose of treatment.

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Participants who achieve clinical remission in Part A will receive vedolizumab IV 300 mg monotherapy, Q8W from Week 30 until Week 46.

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

Findings from Research

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 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]

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]

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 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]

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 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 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 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 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]

References

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

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

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

Adalimumab maintenance therapy for Crohn's disease with intolerance or lost response to infliximab: an open-label study. [2015]

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

Comparative Safety and Effectiveness of Biologic Therapy for Crohn's Disease: A CA-IBD Cohort Study. [2023]

4. England 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. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

The outcome of Crohn's disease patients refractory to anti-TNF and either vedolizumab or ustekinumab. [2021]

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

Real-World Evidence Comparing Vedolizumab and Ustekinumab in Antitumor Necrosis Factor-Experienced Patients With Crohn's Disease. [2023]

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

Real-World Effectiveness and Safety of Ustekinumab in Elderly Crohn's Disease Patients. [2023]

8. England 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. [2022]

9. England 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. [2023]

10. England 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. [2021]

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

An Objective Comparison of Vedolizumab and Ustekinumab Effectiveness in Crohn's Disease Patients' Failure to TNF-Alpha Inhibitors. [2022]