Vedolizumab for Ulcerative Colitis

No longer recruiting at 148 trial locations

Overseen By Takeda Contact

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Takeda

Must not be taking: Anti-integrins, Biologics

Disqualifiers: Neurological disorders, Active infections, TB, 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: 15

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the medication vedolizumab (also known as Entyvio) can help children and teenagers with moderate to severe ulcerative colitis achieve remission, where symptoms improve or disappear. Participants will receive vedolizumab infusions to assess its effectiveness in reducing inflammation and pain in the digestive system. The study will also monitor for any possible side effects of the treatment. Children who have struggled with ulcerative colitis despite current medications might be suitable candidates for the trial. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising treatment.

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 be unresponsive or intolerant to their current standard of care, which might imply changes to your medication routine. It's best to discuss this with the trial coordinators.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that vedolizumab, the treatment under study, is generally well-tolerated. Most side effects are not serious. Rarely, some individuals might experience reactions during the infusion. Although serious infections like sepsis (a severe blood infection) have been reported, they remain uncommon. Vedolizumab has been used to treat Crohn's disease and ulcerative colitis in adults and is considered safe overall. While some risks exist, proper monitoring can manage them effectively. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for ulcerative colitis?

Researchers are excited about vedolizumab for ulcerative colitis because it works differently from current treatments. Unlike most treatments that broadly suppress the immune system, vedolizumab specifically targets a protein called integrin on white blood cells, preventing them from entering the gut and causing inflammation. This targeted approach could reduce side effects and improve the quality of life for patients. Additionally, vedolizumab is administered as an intravenous infusion, which may offer a more controlled delivery compared to oral medications.

What evidence suggests that vedolizumab might be an effective treatment for ulcerative colitis?

Research has shown that vedolizumab can effectively treat ulcerative colitis, which causes inflammation in the digestive tract. One study found that 42% of patients had no symptoms after 52 weeks of treatment. Another study revealed that 88% of those who initially improved remained symptom-free after 104 weeks. These results suggest vedolizumab helps many patients manage their symptoms over the long term. In this trial, participants will receive different dosages of vedolizumab based on their weight, either during the induction or maintenance periods. The treatment targets specific cells in the gut, reducing inflammation and easing pain. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for children and teenagers weighing at least 10 kg with moderate to severe ulcerative colitis diagnosed over a month ago. They must have tried treatments like corticosteroids or TNF-α antagonists without success, or cannot tolerate them. Participants should not have had certain surgeries, live vaccines recently, other biologic treatments too close to the study start, active infections including TB or hepatitis B/C, or any history of neurological disorders.

Inclusion Criteria

My ulcerative colitis is active and not responding to current treatments.

My ulcerative colitis extends beyond the rectum.

My previous treatments for my condition, including steroids or immunomodulators, have not worked or caused side effects.

Exclusion Criteria

I haven't had a serious infection like pneumonia or COVID-19 in the last 30 days.

I haven't taken any experimental or approved biologic drugs recently.

I have had surgery to remove all or part of my colon, or I have a stoma or known narrow section in my intestine.

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

18 weeks

1 visit (in-person or virtual)

Long-term follow-up

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

104 weeks

Every 6 months (in-person or phone call)

What Are the Treatments Tested in This Trial?

Interventions

• Vedolizumab

Trial Overview The trial tests Vedolizumab's effectiveness in achieving remission from ulcerative colitis symptoms in young patients. Remission is when symptoms improve greatly or disappear and an endoscopy shows little to no disease signs. Initially, participants get three infusions over six weeks; responders continue with one of three doses every eight weeks.

How Is the Trial Designed?

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

Vedolizumab 300 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 ≥30 kg who achieved clinical response at Week 14 randomized to this high dose arm group will receive vedolizumab 300 mg.

Group II: Maintenance Period: Participants ≥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 III: Maintenance Period: Participants >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: Participants >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: Participants 10 to 15 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 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: Participants 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: Participants ≥30 kg, Vedolizumab 300 mg Experimental Treatment 1 Intervention

Vedolizumab 300 mg, intravenous (IV) infusion, at Day 1, Weeks 2 and 6 in the Induction Period. Participants with UC having Baseline weight of ≥30 kg are included in this arm.

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

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

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

Vedolizumab 150 mg, IV infusion, at Day 1, Weeks 2 and 6 in the Induction Period. Participants with UC having Baseline weight of 10 to 15 kg are included in this arm.

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 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 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]

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 a study of 336 patients with Crohn's disease and ulcerative colitis, vedolizumab was found to induce endoscopic improvement in 56.1% of ulcerative colitis patients and remission in 39.1% of Crohn's disease patients, indicating its efficacy as a treatment.

Anti-TNF naïve patients experienced significantly better endoscopic outcomes compared to those previously exposed to anti-TNF therapies, suggesting that prior treatment may affect the effectiveness of vedolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Drug Exposure on Vedolizumab-Induced Endoscopic Remission in Anti-Tumour Necrosis Factor [TNF] Naïve and Anti-TNF Exposed IBD Patients. Verstockt, B., Mertens, E., Dreesen, E., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9932778/

Real-world outcomes of 54-week vedolizumab therapy and ... Effectiveness outcomes. At 54-week follow-up, clinical response with vedolizumab was achieved in 62% of patients (n = 62/100) versus 83 ...

2. entyviohcp.com entyviohcp.com/ulcerative-colitis-efficacy

Ulcerative Colitis Clinical Trials for ENTYVIO® (vedolizumab) GEMINI I trial data: 42% of patients achieved clinical remission at Week 52 with. ENTYVIO IV. Placebo. CI=confidence interval; Q8W=every 8 weeks.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6445254/

Vedolizumab for Ulcerative Colitis: Treatment Outcomes ... The overall median time to achieving clinical response, clinical remission, corticosteroid-free remission, and endoscopic remission were 96 days (IQR 53–178), ...

4. academic.oup.com academic.oup.com/ecco-jcc/article/11/4/400/2422318

Long-term Efficacy of Vedolizumab for Ulcerative Colitis Among patients who responded to vedolizumab induction and had data available, 88% [n = 120/136] were in remission after 104 weeks of exposure (96% [n = 70/73] ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1215734

Vedolizumab as Induction and Maintenance Therapy for ... At week 52, this outcome was observed in 31.4% of the patients who received vedolizumab every 8 weeks and in 45.2% of those who received ...

6. entyviohcp.com entyviohcp.com/safety-profile

Safety Profile for ENTYVIO® (vedolizumab) Serious infections have been reported in patients treated with ENTYVIO, including anal abscess, sepsis (some fatal), tuberculosis, salmonella sepsis, Listeria ...

7. 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 ...

8. 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.

9. 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 ...

10. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/entyvio

Entyvio | European Medicines Agency (EMA) Furthermore, the risks are considered manageable, despite the lack of long-term safety data, if recommendations in place are followed. ... Comparative ...