Vedolizumab for Crohn's Disease

Recruiting at 99 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests vedolizumab, a medication designed to reduce inflammation and pain in the digestive system for children and teenagers with moderate to severe Crohn's disease. The researchers aim to determine if symptoms improve or disappear and if an endoscopy (a camera test of the digestive tract) shows no signs of inflammation after treatment. Participants will receive initial infusions and, if they respond well, will continue with either a high or low dose every eight weeks. Those with moderate to severe Crohn's disease that isn’t responding well to current treatments might be a good fit for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to access a potentially effective treatment early.

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.

Is there any evidence suggesting that vedolizumab is likely to be safe for humans?

Past research has shown vedolizumab to be safe for treating conditions like Crohn's disease and ulcerative colitis. The studies did not identify any new safety concerns. Most side effects were mild and not serious. Serious infections occurred rarely, with rates similar to those in people who received a placebo (a treatment with no active medicine).

Vedolizumab is already approved for use in adults with inflammatory bowel diseases, indicating it is generally well-tolerated. However, it is not yet officially approved for use in children, though doctors may prescribe it based on their judgment. This trial aims to further explore its safety and effectiveness in younger patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for Crohn's disease?

Vedolizumab is unique because it targets a specific protein called integrin α4β7, which is involved in the movement of white blood cells into the gut. This targeted approach helps reduce inflammation in Crohn's disease without broadly suppressing the immune system, unlike some current treatments that can affect the whole body and increase infection risk. Researchers are excited because vedolizumab offers a more focused treatment option, potentially leading to fewer side effects and better quality of life for patients with Crohn's disease.

What evidence suggests that vedolizumab might be an effective treatment for Crohn's disease?

Research has shown that vedolizumab can help treat Crohn's disease. In past studies, about 39% of patients were symptom-free after one year of treatment, with some noticing improvements as soon as six weeks. For those who had not used similar treatments before, vedolizumab was likely to help them continue the treatment and achieve symptom relief. Overall, vedolizumab significantly reduced symptoms and inflammation in people with Crohn's disease. Participants in this trial will receive different dosages of vedolizumab based on their weight, as part of various treatment arms, to evaluate its effectiveness further. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

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]

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 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, 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 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]

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

The Safety Profile of Vedolizumab in Ulcerative Colitis and ... Adverse event patterns were consistent with clinical trials, with no new safety concerns. Most reported events were non-serious and event ...

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. entyvio.com entyvio.com/

ENTYVIO® (vedolizumab) for Crohn's Disease or Ulcerative ... ENTYVIO is a biologic treatment for moderate to severe Crohn's disease (CD) or ulcerative colitis (UC). See Safety and Prescribing Information.

10. gut.bmj.com gut.bmj.com/content/66/5/839

The safety of vedolizumab for ulcerative colitis and ... - Gut Vedolizumab has a favourable safety profile with low incidence rates of serious infections, infusion-related reactions and malignancies over an extended ...