Vedolizumab for Crohn's Disease

(VECTORS Trial)

Recruiting at 76 trial locations

Overseen By Elena van Hest

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Alimentiv Inc.

Must be taking: 5-ASA

Must not be taking: Vedolizumab, Etrolizumab, Natalizumab

Disqualifiers: HIV, Hepatitis B/C, Tuberculosis, 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: 86

Duration: 48 weeks

304 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called vedolizumab (also known as Entyvio) for people with Crohn's disease to determine if focusing on gut healing, assessed using a simple ultrasound, leads to better long-term results. Two groups will be compared: one aims for healing based on ultrasound results, symptoms, and lab markers, while the other focuses on symptoms and lab markers only. Suitable candidates have moderate to severe Crohn's, experienced frequent flare-ups, and have not extensively used advanced treatments before. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits 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, but you can continue a stable dose of 5-ASA if it was started at least 4 weeks before screening. It's best to discuss your specific medications with the trial team.

What is the safety track record for Vedolizumab?

Research shows that vedolizumab is generally safe for people with Crohn's disease. Studies have found that it helps reduce symptoms and improve quality of life for many. Most reported side effects have been mild. Specifically, 87% of these side effects were not serious, and patients could continue treatment in 81% of these cases.

Vedolizumab has also been used safely for other conditions, with a well-documented safety record from several clinical trials. Only a small number of patients developed antibodies against the drug, which could make the drug less effective. Reactions at the injection site, such as minor skin issues, were reported but were not common.

Overall, vedolizumab appears well-tolerated with few serious side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Vedolizumab is unique because it specifically targets the gut by blocking a protein called integrin, which is involved in the inflammation process of Crohn's Disease. Unlike traditional treatments such as corticosteroids or immunosuppressants, which can affect the entire body and lead to various side effects, Vedolizumab provides a more focused approach, potentially reducing side effects by concentrating its action on the digestive tract. Researchers are excited about this treatment because it offers a targeted strategy that could lead to effective management of Crohn's Disease symptoms while minimizing broader systemic impacts.

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

Research has shown that vedolizumab effectively treats Crohn's disease. In one study, 39% of patients taking vedolizumab achieved remission after one year, compared to 22% of those on a placebo (a non-active treatment). Another study found that patients who had not previously used similar drugs had a better chance of staying on vedolizumab and achieving remission. Vedolizumab has proven safe and effective, with many patients experiencing benefits at 30 and 52 weeks. This trial will evaluate vedolizumab in two groups: one aiming for corticosteroid-free clinical remission and biomarker remission, and the other targeting corticosteroid-free IUS-based outcomes, clinical remission, and biomarker remission. Overall, vedolizumab has a strong track record for helping people with Crohn's disease achieve remission, even without steroids. ^{2 6 7 8 9}

Who Is on the Research Team?

Vipul Jairath

Principal Investigator

Alimentiv Inc.

Are You a Good Fit for This Trial?

Adults aged 18-80 with moderately-to-severely active Crohn's Disease, evidenced by specific ultrasound and biomarker levels. Participants can be biologic-naïve or have limited prior treatment with advanced therapies for CD. They must not be pregnant and agree to use effective contraception.

Inclusion Criteria

I have not used many advanced therapy drugs.

I am taking a stable dose of 5-ASA for Crohn's Disease.

I can take part in all parts of the study without restrictions.

Exclusion Criteria

I have a gastrointestinal condition.

I do not have any current infections.

I have been treated with at least 2 advanced cancer drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are treated over 48 weeks to achieve corticosteroid-free outcomes, including IUS-based outcomes, clinical remission, and biomarker remission.

48 weeks

Regular visits at Weeks 22, 30, 38, and 48

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including IBDQ score and adverse events.

48 weeks

Follow-up visits at Weeks 64, 80, and 96

What Are the Treatments Tested in This Trial?

Interventions

• Vedolizumab

Trial Overview The trial is testing if targeting transmural healing using vedolizumab plus monitoring with intestinal ultrasound, clinical symptoms, and biomarkers leads to better outcomes than just targeting clinical symptoms and biomarkers without the ultrasound component.

How Is the Trial Designed?

Group I: Group 2: Corticosteroid-free clinical remission + biomarker remission. Experimental Treatment 1 Intervention

Group 2 will be treated over 48 weeks to achieve a target of corticosteroid-free clinical remission + biomarker remission.

Group II: Group 1: Corticosteroid-free IUS-based outcomes + clinical remission + biomarker remission Experimental Treatment 1 Intervention

Group 1 will be treated over 48 weeks to achieve a target of corticosteroid-free IUS-based outcomes + clinical remission + biomarker remission. At Week 22 and 30, the IUS-based component of the target will be IUS response and at Week 38, the final treatment target will be TMH.

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?

Alimentiv Inc.

Lead Sponsor

Trials

15

Recruited

3,300+

Takeda

Industry 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

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]

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 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]

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]

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... These real-world data on first-line biologics show no differences in 12-month effectiveness outcomes for vedolizumab- vs. infliximab-treated biologic-naive ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11580093/

Effectiveness and safety outcomes after long-term (54 ... Overall, VDZ effectively reduced CD symptoms and improved the patients' quality of life while showing clinical effectiveness and a safety ...

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

Safety Profile for ENTYVIO® (vedolizumab) Proven safety profile based on 4 clinical trials · The incidence of anti-drug antibodies with ENTYVIO SC for UC and Crohn's was 3.4% (13/381) · ISRs were reported ...

8. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2796853

Comparative Outcomes and Safety of Vedolizumab vs ... This study suggests that vedolizumab is associated with a higher risk of treatment failure compared with TNF antagonists, without offering any safety advantage ...

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

An update on the safety of long-term vedolizumab use in ... Of all reported AEs, 87% were non-serious and vedolizumab was continued in 81% of these cases, indicating high treatment persistence and suggested AEs were non- ...