Vedolizumab for Crohn's Disease

Recruiting in Palo Alto (17 mi)

+87 other locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Takeda

Must not be taking: Biologics, Live vaccines

Disqualifiers: Neurological disorders, Active infections, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

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.

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.

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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.

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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.

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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

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Boston Children's Hospital Boston, MA

Childrens Center For Digestive Healthcare Atlanta, GA

Johns Hopkins University Baltimore, MD

Phoenix Childrens Hospital Phoenix, AZ

More Trial Locations

Who Is Running the Clinical Trial?

Takeda Lead Sponsor

References

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

Vedolizumab as a Treatment for Crohn's Disease and Ulcerative Colitis. [2022] The management of Crohn's disease and ulcerative colitis has become increasingly complex. With the current utilization of immunosuppressive therapies earlier in the disease course for patients presenting with moderate to severe disease, there is a great need for additional biologic agents targeting inflammatory mediators other than anti-tumor necrosis factor-α (anti-TNF) agents. Although anti-TNF agents have positively impacted the treatment of inflammatory bowel disease, many patients can lose their response or develop intolerance to these agents over time through the formation of antidrug antibodies. Furthermore, a sizeable percentage of patients are primary nonresponders to anti-TNF drugs. Vedolizumab (Entyvio, Takeda Pharmaceuticals), a monoclonal antibody to the α4β7 integrin, inhibits gut lymphocyte trafficking and has been demonstrated to be an effective and safe agent for the treatment of both Crohn's disease and ulcerative colitis. This article reviews the clinical trial evidence and rationale for the use of vedolizumab in moderate to severe Crohn's disease and ulcerative colitis.

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

Vedolizumab: first global approval. [2021] Vedolizumab [Entyvio(®) (US, Europe)], a humanized monoclonal antibody α4β7 integrin receptor antagonist, has been developed by Millennium Pharmaceuticals (d/b/a Takeda Pharmaceuticals International) for the treatment of ulcerative colitis and Crohn's disease. Vedolizumab has received its first global approval for the treatment of ulcerative colitis and Crohn's disease in the US, for use in adult patients with moderate-to-severe disease who have had an inadequate response, loss of response or intolerance to one or more standard therapies (corticosteroids, immunomodulators or tumour necrosis factor-α inhibitor) or demonstrated dependence on corticosteroids. Vedolizumab has since been approved for ulcerative colitis and Crohn's disease in the EU, Norway, Iceland and Liechtenstein. This article summarizes the milestones in the development of vedolizumab leading to its first approval for the treatment of ulcerative colitis and Crohn's disease.

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] Vedolizumab (Entyvio™) is a humanized monoclonal antibody α4β7 integrin-receptor antagonist indicated for the treatment of adult patients with moderately to severely active ulcerative colitis or Crohn's disease. This article reviews the pharmacological properties of intravenous infusions of vedolizumab and its clinical efficacy in adult patients with these diseases. In phase III clinical trials, patients with ulcerative colitis had significantly higher rates of clinical response and clinical remission when treated with vedolizumab than when receiving placebo at both 6 and 52 weeks. However, outcomes with vedolizumab in patients with Crohn's disease were mixed. In a study that evaluated both clinical remission rate and CDAI-100 response rate as primary endpoints, only the clinical remission rate at 6 weeks was significantly higher with vedolizumab than placebo. In another trial, there was no significant between-group difference in the clinical remission rate in TNF-antagonist failure patients at 6 weeks (primary endpoint), although there was a significant difference at 10 weeks. In the Crohn's disease study that included maintenance treatment, vedolizumab was significantly more effective at 52 weeks than placebo in both endpoints (clinical remission was the only primary endpoint in the maintenance study). Vedolizumab was generally well tolerated in these trials. As vedolizumab is a specific α4β7 integrin antagonist, with gut-specific effects, it is unlikely to be associated with the development of progressive multifocal leukoencephalopathy, a risk observed with the less selective α4β7/α4β1 integrin antagonist natalizumab. Vedolizumab is a useful addition to the treatment options available for patients with moderately to severely active ulcerative colitis and Crohn's disease.

4. England pubmed.ncbi.nlm.nih.gov

Low Frequency of Opportunistic Infections in Patients Receiving Vedolizumab in Clinical Trials and Post-Marketing Setting. [2023] Vedolizumab (ENTYVIO) is a humanized α4β7 integrin antagonist approved for the treatment of inflammatory bowel disease, which selectively blocks gut-specific lymphocyte trafficking. We evaluated the risk of opportunistic infections of interest in patients treated with vedolizumab.

5. England pubmed.ncbi.nlm.nih.gov

An update on the safety of long-term vedolizumab use in inflammatory bowel disease. [2023] Vedolizumab (Entyvio) is a humanized monoclonal antibody that disrupts the interaction between α4β7 integrin on circulating T-lymphocytes and MAdCAM-1 on the vascular endothelium to prevent their egress to sites of gut inflammation. It has proven therapeutic efficacy for the treatment of moderate-to-severe Crohn's disease, ulcerative colitis, and pouchitis.

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] Vedolizumab is the first gut-selective integrin blocker indicated for patients with Crohn's disease (CD) and ulcerative colitis (UC). This study aimed to examine the adverse events (AEs) profile of vedolizumab compared to anti-tumor necrosis factors (anti-TNFs) indicated for CD and UC using the FDA Adverse Event Reporting System (FAERS) database. AE reports with vedolizumab (5/20/2014-6/30/2015) and CD/UC-indicated anti-TNF drugs (adalimumab, infliximab, certolizumab pegol, and golimumab, during 8/1/1998-6/30/2015) as primary suspects were extracted from the FAERS database. AEs associated with vedolizumab were compared for signals of disproportionate reporting against anti-TNF drugs and all other drugs (1969-6/30/2015), using the proportional reporting ratio (PRR) and the empirical Bayesian geometric mean (EBGM) algorithms. The search retrieved 499 reports for vedolizumab and 119,620 reports for anti-TNFs, with 35.9% and 32.1% of these, respectively, being serious AEs. With the PRR approach, vedolizumab-associated reports had signals for 22 groups of AEs (9 were associated with serious outcomes) relative to anti-TNFs and had 34 signals relative to all other drugs. Signals detected included those reported as warnings in prescribing information and new AEs related to cardiovascular disease. Due to the voluntary nature of FAERS, this finding should be considered hypothesis generating (rather than hypothesis testing). Longer-term observational studies are required to evaluate the safety of vedolizumab.