Vedolizumab for Crohn's Disease

Overseen By Billy D Nix

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Washington University School of Medicine

Must be taking: Vedolizumab

Disqualifiers: Pregnancy, Colonic involvement, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 14 weeks

48 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants can be on vedolizumab with or without thiopurines or methotrexate, which suggests you might be able to continue some medications.

What data supports the effectiveness of the drug Vedolizumab for Crohn's Disease?

Vedolizumab has been shown to be effective for treating Crohn's disease, especially in patients who have not responded well to other treatments. In clinical trials, it was more effective than a placebo in achieving clinical remission at 6 weeks and maintaining it at 52 weeks. ^{1 2 3 4 5}

Is Vedolizumab safe for humans?

Vedolizumab (also known as Entyvio) has been shown to be generally safe for treating Crohn's disease and ulcerative colitis, with a low frequency of serious infections. However, some adverse events have been reported, including those related to cardiovascular issues, so longer-term studies are needed to fully understand its safety profile. ^{2 3 4 5 6}

How is the drug Vedolizumab unique for treating Crohn's disease?

Vedolizumab is unique because it specifically targets the α4β7 integrin, which helps prevent immune cells from reaching the gut and causing inflammation, making it different from other treatments that target broader immune responses. This gut-specific action reduces the risk of certain side effects seen with other treatments, like progressive multifocal leukoencephalopathy, a brain infection risk associated with less selective drugs. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial aims to guide doctors on using vedolizumab for patients with small bowel Crohn's Disease. Vedolizumab helps reduce intestinal inflammation by blocking specific cells. The study will also explore new ways to predict and monitor long-term treatment success. Vedolizumab has been a standard treatment for inflammatory bowel diseases like Crohn's disease and ulcerative colitis.

Research Team

Parakkal Deepak, MBBS, MS

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults over 18 with moderate to severe Crohn's Disease affecting only the small bowel or ileocecal area, who are starting treatment with Vedolizumab, possibly alongside thiopurines or methotrexate. It excludes those unable to consent, pregnant individuals, patients with colonic involvement beyond the ascending colon and cecum, contraindications for MRE like chronic kidney disease or incompatible medical devices, and anyone planning surgery before follow-up MRE.

Inclusion Criteria

I am currently taking Vedolizumab, with or without thiopurines or methotrexate.

My Crohn's disease affects only my small bowel or ileocecal area, confirmed by an MRE.

Exclusion Criteria

I am under 18 years old.

I am scheduled for surgery before my first follow-up MRE.

I have Crohn's disease affecting the area around my anus.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vedolizumab 300 mg IV at 0, 2, and 6 weeks, followed by maintenance dosing at week 14

14 weeks

4 visits (in-person)

Follow-up

Participants are monitored for radiological transmural response and clinical remission

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Vedolizumab

Trial Overview The study aims to evaluate how well Vedolizumab works in treating small bowel Crohn's Disease using MR enterography as a measure of response. It also seeks to develop predictive models based on clinical data and imaging/endoscopic findings that could forecast long-term remission. Additionally, it will explore potential new biomarkers in blood that correlate with radiological responses.

Participant Groups

Group I: Vedolizumab 300 MG Injection [Entyvio] Experimental Treatment 1 Intervention

Vedolizumab will be initiated at 300 mg intravenous (IV) dosing at 0, 2 and 6 weeks followed by the 1st maintenance with 300 mg IV at week 14. Patients who have not achieved clinical response at week 14 will be eligible to undergo dose escalation to 4 weekly dosing of vedolizumab depending on the judgement of the treating gastroenterologist.

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

Approved in European Union as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Approved in United States as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Approved in Canada as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Approved in Japan as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Findings from Research

In phase III clinical trials, vedolizumab significantly improved clinical response and remission rates in patients with ulcerative colitis compared to placebo at both 6 and 52 weeks, demonstrating its efficacy for this condition.

While vedolizumab showed mixed results for Crohn's disease, it was effective in achieving clinical remission at 52 weeks in maintenance treatment, and it is generally well tolerated, with a lower risk of serious side effects compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab: a review of its use in adult patients with moderately to severely active ulcerative colitis or Crohn's disease. Garnock-Jones, KP.[2016]

Vedolizumab is a monoclonal antibody that effectively targets the α4β7 integrin to inhibit gut lymphocyte trafficking, providing a safe treatment option for patients with moderate to severe Crohn's disease and ulcerative colitis.

Unlike anti-TNF agents, which some patients may become intolerant to or lose response over time, vedolizumab offers a promising alternative for those who are primary nonresponders or have developed antidrug antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab as a Treatment for Crohn's Disease and Ulcerative Colitis. Ha, C., Kornbluth, A.[2022]

Vedolizumab is a humanized monoclonal antibody that targets the α4β7 integrin receptor, specifically designed for treating moderate-to-severe ulcerative colitis and Crohn's disease in adults who have not responded well to standard therapies.

It has received global approval, including in the US and EU, for patients who have had inadequate responses to other treatments, highlighting its role as an important option for those with difficult-to-treat inflammatory bowel diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab: first global approval. Poole, RM.[2021]

In patients treated with vedolizumab, the incidence of opportunistic infections was low, at 0.7 per 100 patient-years in clinical trials and 1.0 in long-term safety studies, indicating a favorable safety profile for this medication.

No cases of serious infections like progressive multifocal leukoencephalopathy or hepatitis B/C viral reactivation were reported, and most patients continued treatment without significant issues, suggesting vedolizumab is a safe option for managing inflammatory bowel disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Frequency of Opportunistic Infections in Patients Receiving Vedolizumab in Clinical Trials and Post-Marketing Setting. Ng, SC., Hilmi, IN., Blake, A., et al.[2023]

Vedolizumab is an effective treatment for moderate-to-severe inflammatory bowel diseases like Crohn's disease and ulcerative colitis, with a well-established safety profile based on extensive clinical trial data and real-world studies.

The safety data indicates no unexpected long-term risks, making vedolizumab a strong candidate for combination therapies in patients with complex or refractory cases of inflammatory bowel disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the safety of long-term vedolizumab use in inflammatory bowel disease. Honap, S., Netter, P., Danese, S., et al.[2023]

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]

References

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

Vedolizumab: a review of its use in adult patients with moderately to severely active ulcerative colitis or Crohn's disease. [2016]

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

Vedolizumab as a Treatment for Crohn's Disease and Ulcerative Colitis. [2022]

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

Vedolizumab: first global approval. [2021]

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

Low Frequency of Opportunistic Infections in Patients Receiving Vedolizumab in Clinical Trials and Post-Marketing Setting. [2023]

5. England pubmed.ncbi.nlm.nih.gov

An update on the safety of long-term vedolizumab use in inflammatory bowel disease. [2023]

6. 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]