Vedolizumab for Crohn's Disease

Recruiting at 87 trial locations

Overseen By Takeda Contact

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Takeda

Must not be taking: Biologics, Live vaccines

Disqualifiers: Neurological disorders, Active infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 8

120 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 should have been unresponsive or intolerant to their current standard treatments, which might imply a change in medication. It's best to discuss your specific situation with the trial coordinators.

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. This gut-specific action reduces the risk of certain side effects seen with less selective treatments. ^{1 2 3 4 5}

What is the purpose of this trial?

Vedolizumab is a medicine that helps to reduce inflammation and pain in the digestive system. In this study, children and teenagers with moderate to severe Crohn's disease will be treated with vedolizumab. The main aim of the study is to check if participants achieve remission after treatment with the vedolizumab. Remission means symptoms improve or disappear and an endoscopy shows no signs of inflammation. Participants will receive 3 infusions of vedolizumab over 6 weeks. Then, those who have a clinical response will receive either a high dose or low dose of vedolizumab once every 8 weeks. They will receive the same dose every time.

Eligibility Criteria

This trial is for children and teenagers with moderate to severe Crohn's disease who haven't responded well to standard treatments like corticosteroids, immunomodulators, or TNF-α antagonists. They should weigh at least 10 kg and have been diagnosed with CD at least a month prior. Participants must be up-to-date on vaccinations but can't join if they've had certain surgeries, other conditions like TB or hepatitis B/C, recent infections including COVID-19, or any history of malignancy.

Inclusion Criteria

I weigh at least 10 kg.

I've had severe colitis for over 8 years and had a colonoscopy in the last year.

I've tried and not responded well to certain medications for my condition.

Exclusion Criteria

- A TB skin test reaction ≥5 mm.

I have been diagnosed with indeterminate colitis.

- Positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests, OR

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive 3 doses of vedolizumab IV infusion at Day 1, Week 2, and Week 6 based on their weight at Baseline

6 weeks

3 visits (in-person)

Maintenance

Participants who achieve clinical response receive vedolizumab IV infusions every 8 weeks up to Week 46

32 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a safety visit 18 weeks after the last dose

18 weeks

Long-term Follow-up

Participants may enter an observational long-term follow-up period of 2 years after the last dose of study drug

104 weeks

Treatment Details

Interventions

• Vedolizumab

Trial Overview The study tests Vedolizumab IV in young patients with Crohn's Disease. Initially, all participants receive three infusions over six weeks. Those responding will continue receiving either a high dose or low dose every eight weeks. The goal is to see if the treatment leads to remission—meaning their symptoms improve significantly or disappear entirely.

Participant Groups

Group I: Maintenance Period: ≥30 kg: Vedolizumab 150 mg Experimental Treatment 1 Intervention

Vedolizumab 150 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of ≥30 kg who achieved clinical response at Week 14 randomized to this low dose arm group will receive vedolizumab 150 mg.

Group II: Maintenance Period: ≥30 kg, Vedolizumab 300 mg Experimental Treatment 1 Intervention

Vedolizumab 300 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of ≥30 kg who achieved clinical response at Week 14 randomized to this high dose arm group will receive vedolizumab 300 mg.

Group III: Maintenance Period: >15 to <30 kg, Vedolizumab 200 mg Experimental Treatment 1 Intervention

Vedolizumab 200 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of \>15 to \<30 kg who achieved clinical response at Week 14 randomized to this high dose arm group will receive vedolizumab 200 mg.

Group IV: Maintenance Period: >15 to <30 kg Vedolizumab 100 mg Experimental Treatment 1 Intervention

Vedolizumab 100 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of \>15 to \<30 kg who achieved clinical response at Week 14 randomized to this low dose arm group will receive vedolizumab 100 mg.

Group V: Maintenance Period: 10 to 15 kg Vedolizumab 150 mg Experimental Treatment 1 Intervention

Vedolizumab 150 mg, IV infusion, once every 8 weeks (Q8W) from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of 10 to 15 kg who achieved clinical response at Week 14 randomized to this high dose arm group will receive vedolizumab 150 mg.

Group VI: Maintenance Period: 10 to 15 kg Vedolizumab 100 mg Experimental Treatment 1 Intervention

Vedolizumab 100 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of 10 to 15 kg who achieved clinical response at Week 14 randomized to this low dose arm group will receive vedolizumab 100 mg.

Group VII: Induction Period: ≥30 kg, Vedolizumab 300 mg Experimental Treatment 1 Intervention

Vedolizumab 300 mg, IV infusion, at Day 1, Weeks 2 and 6 in Induction Period. Participants with CD having Baseline weight of ≥30 kg will be included in this arm group.

Group VIII: Induction Period: >15 to <30 kg, Vedolizumab 200 mg Experimental Treatment 1 Intervention

Vedolizumab 200 mg, IV infusion, at Day 1, Weeks 2 and 6 in Induction Period. Participants with CD having Baseline weight of \>15 to \<30 kg will be included in this arm group.

Group IX: Induction Period: 10 to 15 kg, Vedolizumab 150 mg Experimental Treatment 1 Intervention

Vedolizumab 150 mg, intravenous (IV) infusion, at Day 1, Weeks 2 and 6 in Induction Period. Participants with CD having Baseline weight of 10 to 15 kg will be included in this arm group.

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?

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

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]