Vedolizumab for Crohn's Disease

No longer recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests vedolizumab, a medication studied for its effectiveness in treating Crohn's disease affecting the small bowel. The goal is to determine if vedolizumab can lead to long-term improvement and to identify new blood markers that could predict the treatment's effectiveness over time. Suitable participants have Crohn's disease limited to the small bowel or ileocecal area and are beginning treatment with vedolizumab. As a Phase 4 trial, this research aims to understand how an FDA-approved and effective treatment can benefit more patients.

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 is the safety track record for vedolizumab?

Research has shown that vedolizumab is generally safe. Studies found that people using vedolizumab experienced slightly higher infection rates than those taking a placebo, but these were not significantly concerning. Serious infections occurred rarely, and most participants tolerated the treatment well.

A meta-analysis, which combines results from several studies, found that serious infections and reactions to the drug were uncommon. Overall, vedolizumab is considered safe and effective for adults with inflammatory bowel diseases like Crohn's disease.

While health authorities have not yet approved vedolizumab for children, they have approved it for adults, indicating strong confidence in its safety for adult patients. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Vedolizumab is unique because it specifically targets the gut, reducing inflammation by blocking a protein called integrin α4β7. Unlike other treatments for Crohn's disease, which might suppress the immune system more broadly, Vedolizumab focuses on the gastrointestinal tract, potentially minimizing side effects. Researchers are excited about its ability to provide relief for patients who haven't responded well to standard treatments like corticosteroids or TNF inhibitors. Additionally, the option for dose escalation offers flexibility in managing the disease based on individual patient needs.

What is the effectiveness track record for vedolizumab in treating small bowel Crohn's disease?

Research has shown that vedolizumab effectively treats Crohn's disease. In one study, 39% of participants taking vedolizumab went into remission after a year, compared to 22% of those taking a placebo (a pill with no active medicine). Another study found that individuals who had not previously used similar drugs had a better chance of staying on vedolizumab and reaching remission. Additionally, vedolizumab helped many patients achieve remission as early as six weeks. Overall, vedolizumab is considered a strong option for managing Crohn's disease symptoms. ^{6 7 8 9 10}

Who Is on the Research Team?

Parakkal Deepak, MBBS, MS

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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, 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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7350040/

Good efficacy and safety of vedolizumab in Crohn's ... We obtained a clinical benefit in 68.1%, 68.1% and 59.4% of CD patients and in 68.7%, 54.2% and 54.1% of UC patients after induction, and at 30 weeks and 52 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39102457/

Real-world Clinical Effectiveness and Safety of ... Biologic-naive patients with CD treated with vedolizumab demonstrated a greater likelihood of drug persistence and achieving clinical remission.

3. entyviohcp.com entyviohcp.com/crohns-disease-efficacy

Crohn's Disease Clinical Trials for ENTYVIO® (vedolizumab) Many patients taking ENTYVIO IV achieved remission at Week 52 vs placebo, some without steroids. Some achieved remission at Week 6.

4. entyvio.com entyvio.com/crohns-disease

ENTYVIO® Treatment Results for Crohn's Disease 39% of people on ENTYVIO achieved remission* at 1 year of treatment, compared to 22% of people on placebo. IMPORTANT SAFETY INFORMATION. Do not receive ENTYVIO® ...

5. journals.lww.com journals.lww.com/eurojgh/fulltext/2024/03000/effectiveness_and_safety_of_vedolizumab_and.4.aspx

Effectiveness and safety of vedolizumab and infliximab in... There were no differences in 12-month effectiveness outcomes between vedolizumab and infliximab treatment groups for patients with complicated and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31504340/

The Safety Profile of Vedolizumab in Ulcerative Colitis and ... Overall, 5230 [14%; Crohn's disease] and 3580 [10%; ulcerative colitis] events were serious. Most frequently reported were gastrointestinal ...

7. entyviohcp.com entyviohcp.com/safety-profile

Safety Profile for ENTYVIO® (vedolizumab) Proven safety profile based on 4 clinical trials · INFECTIONS. Infection rates with ENTYVIO were 0.85 per patient-year vs 0.7 for placebo · SERIOUS INFECTIONS.

8. tandfonline.com tandfonline.com/doi/full/10.1080/14740338.2023.2247976

An update on the safety of long-term vedolizumab use in ... Vedolizumab is a safe and effective therapy for adult IBD patients, but its use in pediatric patients remains off-label despite receiving regulatory approval ...

9. takeda.com takeda.com/newsroom/newsreleases/2017/meta-analysis-using-real-world-data-evaluates-safety-profile-of-entyvio-vedolizumab-in-patients-with-moderate-to-severe-ulcerative-colitis-or-crohns-disease/

Meta-Analysis Using Real-World Data Evaluates Safety ... In this case, vedolizumab real-world data were systematically collected and analyzed with the rates of serious infections, infusion-related ...

10. bmcgastroenterol.biomedcentral.com bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-023-03032-7

Effectiveness and safety of vedolizumab induction with or ... In this retrospective study, VDZ alone and VDZ + BUD showed similar high remission rates in patients with moderately to severely active CD.