Vedolizumab for Crohn's Disease

(VECTORS Trial)

Recruiting at 67 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

Trial Summary

What is the purpose of this trial?

Transmural healing (TMH) is recognized as a potentially important measure of Crohn's disease (CD) activity but not a formal target. Observational studies suggest that TMH may be associated with better long-term outcomes. The study will evaluate TMH using noninvasive intestinal ultrasound (IUS), a patient-friendly technique that can be performed routinely in clinical practice. The aim of the study is to determine if treating to a target of corticosteroid-free (CS-free) IUS outcomes + clinical symptoms + biomarkers is superior to a target of clinical symptoms + biomarkers alone in achieving CS-free endoscopic remission measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD). Qualified participants will be randomly assigned in a 1:1 ratio to one of 2 different target treatment groups. Group 1: Participants 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. Group 2: Participants will be treated over 48 weeks to achieve a target of corticosteroid-free clinical remission + biomarker remission.

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

Vedolizumab has been shown to be effective in 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 and 52 weeks, particularly in maintenance treatment. ^{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. ^{1 2 4 5 6}

How is the drug Vedolizumab unique in 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. ^{1 2 3 4 5}

Research Team

Vipul Jairath

Principal Investigator

Alimentiv Inc.

Eligibility Criteria

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 am using effective birth control and my pregnancy test was negative.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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

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

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

Vedolizumab: first global approval. [2021]

3. 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]

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]