Vedolizumab for Ulcerative Colitis and Crohn's Disease

Recruiting at 56 trial locations

Overseen By Takeda Contact

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Takeda

Must not be taking: Anti-integrins, MAdCAM-1 antagonists

Disqualifiers: Neurological disorders, Tuberculosis, Hepatitis B, 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

Compensation: Varies

Number of Visits: 9

70 Participants Needed

Trial Summary

What is the purpose of this trial?

The main aim of this study is to learn how the body of a child or teenager with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD) processes vedolizumab (pharmacokinetics) given just under the skin subcutaneously (SC). The participants will be treated with vedolizumab for up to 34 weeks. During the study, participants will visit their study clinic several times.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should have failed or been intolerant to certain treatments like corticosteroids or TNF-α antagonists, which might imply some changes to your current medication plan. It's best to discuss this with the trial coordinators.

What data supports the effectiveness of the drug Vedolizumab for treating ulcerative colitis and Crohn's disease?

Research shows that Vedolizumab, a drug targeting gut inflammation, is effective for ulcerative colitis and Crohn's disease, with studies indicating it helps patients achieve remission without the need for steroids. Long-term and real-world studies also support its safety and effectiveness in managing these conditions. ^{1 2 3 4 5}

Is vedolizumab safe for humans?

Vedolizumab has been shown to be generally safe for people with ulcerative colitis and Crohn's disease, with studies noting its safety in both short-term and long-term use. ^{6 7 8 9 10}

What makes the drug vedolizumab unique for treating ulcerative colitis and Crohn's disease?

Vedolizumab is unique because it is a gut-selective drug that works by blocking certain immune cells from entering the gut, which helps reduce inflammation specifically in the digestive tract. This makes it different from other treatments that affect the entire immune system. ^{3 8 11 12 13}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

This trial is for children and teenagers with moderately to severely active ulcerative colitis or Crohn's disease. They must weigh at least 10 kg, have a specific severity of their condition as measured by medical scores, and have tried other treatments like corticosteroids without success. Their vaccinations need to be up-to-date.

Inclusion Criteria

Participants with vaccinations that are up-to-date based on the countrywide accepted schedule of childhood vaccines

I weigh at least 10 kg.

I was diagnosed with UC or CD over a month ago and my condition is moderate to severe.

Exclusion Criteria

I have been diagnosed with indeterminate colitis.

Participants with positive Clostridioides difficile stool test at screening visit

Participants with hypersensitivity or allergies to vedolizumab or any of its excipients

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

6 weeks

3 visits (in-person)

Maintenance

Participants receive vedolizumab 108 mg SC injection every 2 or 4 weeks based on weight

20 weeks

5-10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 weeks

1 visit (in-person)

Extension

Participants may be eligible to receive continued treatment with vedolizumab SC in an extension study

Treatment Details

Interventions

• Vedolizumab

Trial Overview The study tests how vedolizumab, given under the skin (subcutaneously), affects young patients with ulcerative colitis or Crohn's disease over a period of up to 34 weeks. The focus is on understanding how their bodies process the medication.

Participant Groups

Group I: Maintenance Period: Participants ≥30 kg, Vedolizumab 108 mg SC Q2W Experimental Treatment 1 Intervention

Participants with clinical response at Week 14 weighing ≥30 kg will receive vedolizumab 108 mg, SC injection, Q2W from Week 14 to Week 32 in the Maintenance Period.

Group II: Maintenance Period: Participants ≥10 to <30 kg, Vedolizumab 108 mg SC Q4W Experimental Treatment 1 Intervention

Participants with clinical response at Week 14 weighing ≥10 to \<30 kg will receive vedolizumab 108 mg, SC injection, Q4W from Week 14 to Week 30 in the Maintenance Period.

Group III: Induction Period: Participants ≥30 kg, Vedolizumab (High Dose) IV Experimental Treatment 1 Intervention

Participants weighing ≥30 kg will receive vedolizumab (High Dose) IV infusion, at Day 1, Weeks 2 and 6 in the Induction Period.

Group IV: Induction Period: Participants ≥10 to ≤15 kg, Vedolizumab (Low Dose) IV Experimental Treatment 1 Intervention

Participants weighing ≥10 to ≤15 kg will receive vedolizumab (Low Dose), IV infusion, at Day 1, Weeks 2 and 6 in the Induction Period.

Group V: Induction Period: Participants >15 to <30 kg, Vedolizumab (Medium Dose) IV Experimental Treatment 1 Intervention

Participants weighing \>15 to \<30 kg will receive vedolizumab (Medium Dose), IV infusion, at Day 1, Weeks 2 and 6 in the Induction Period.

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

In a study of 258 inflammatory bowel disease patients on maintenance vedolizumab, those in clinical and biochemical remission had significantly higher drug concentrations (12.7 µg/mL) compared to those with active disease (10.1 µg/mL), indicating a strong association between higher vedolizumab levels and remission.

Patients with vedolizumab concentrations above 11.5 µg/mL were nearly 2.4 times more likely to achieve corticosteroid-free clinical and biochemical remission, suggesting that maintaining adequate drug levels is crucial for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher Trough Vedolizumab Concentrations During Maintenance Therapy are Associated With Corticosteroid-Free Remission in Inflammatory Bowel Disease. Ungaro, RC., Yarur, A., Jossen, J., et al.[2020]

In a real-world study of 132 patients with moderate to severe Crohn's disease (CD) and ulcerative colitis (UC), vedolizumab showed sustained clinical response, with 35% of UC patients and 31% of CD patients achieving steroid-free remission after 12 months.

Mucosal healing was observed in 52% of UC patients and 30% of CD patients, indicating that vedolizumab is effective in promoting healing in the intestines, with most adverse events being minor and 74% of patients continuing treatment after one year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab as Induction and Maintenance for Inflammatory Bowel Disease: 12-month Effectiveness and Safety. Christensen, B., Colman, RJ., Micic, D., et al.[2020]

In a study of 53 patients with ulcerative colitis and Crohn's disease receiving vedolizumab therapy, 20% of ulcerative colitis patients and 14.3% of Crohn's disease patients achieved remission by week 30, indicating some efficacy in a treatment-refractory population.

Despite some patients responding to vedolizumab, a significant portion (48% for ulcerative colitis and 39.4% for Crohn's disease) did not respond satisfactorily, highlighting the need for alternative treatment options for those not achieving remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Outcomes of Vedolizumab Therapy in Ulcerative Colitis and Crohn's Disease at a Tertiary Referral Center. Hoffmann, P., Krisam, J., Stremmel, W., et al.[2018]

In a long-term study involving 72 patients with ulcerative colitis (UC) and Crohn's disease (CD), vedolizumab demonstrated significant clinical efficacy, with 39% of patients achieving a clinical response and 58.3% achieving clinical remission after treatment.

Vedolizumab was well-tolerated over the treatment period of up to 78 weeks, with no deaths or serious infections reported, indicating a favorable safety profile similar to previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term clinical experience with vedolizumab in patients with inflammatory bowel disease. Parikh, A., Fox, I., Leach, T., et al.[2022]

In a study of 1095 biologic-naïve patients with ulcerative colitis (UC) and Crohn's disease (CD) over 24 months, vedolizumab and anti-TNFα agents showed similar effectiveness in managing disease symptoms.

However, vedolizumab was associated with significantly lower rates of serious adverse events and serious infections, indicating a more favorable safety profile compared to anti-TNFα treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab and Anti-Tumour Necrosis Factor α Real-World Outcomes in Biologic-Naïve Inflammatory Bowel Disease Patients: Results from the EVOLVE Study. Bressler, B., Yarur, A., Silverberg, MS., et al.[2022]

In a study of 1087 patients with Crohn's disease and ulcerative colitis, vedolizumab demonstrated a favorable safety profile, with a low overall infection rate of 6.3% and non-infectious adverse events primarily being arthralgias (2.9%).

Factors such as active smoking and the use of multiple immunosuppressive agents were found to significantly increase the risk of infections in patients receiving vedolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Analysis of Safety of Vedolizumab in Patients With Inflammatory Bowel Diseases. Meserve, J., Aniwan, S., Koliani-Pace, JL., et al.[2021]

Vedolizumab has been shown to be effective in managing ulcerative colitis, providing significant improvements in patient symptoms and disease control.

The review also highlights that vedolizumab has a favorable safety profile, making it a suitable treatment option for patients with ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of vedolizumab for the treatment of ulcerative colitis. Lau, MS., Tsai, HH.[2020]

Vedolizumab is an effective treatment for moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), helping to induce and maintain clinical response and remission, as shown in multiple phase trials.

The drug is generally well tolerated, with common side effects including nasopharyngitis and headache, but it has not been linked to serious conditions like progressive multifocal leukoencephalopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab: an α4β7 integrin inhibitor for inflammatory bowel diseases. Smith, MA., Mohammad, RA.[2018]

In a study involving 311 patients with ulcerative colitis (UC) and Crohn's disease (CD), vedolizumab demonstrated high treatment persistence, with 93.9% of UC patients and 91.6% of CD patients remaining on a reduced dosing schedule of every 8 weeks after 2 years.

The safety profile of vedolizumab remained consistent with previous studies, showing infrequent adverse events and low relapse rates of 9.1% for UC and 14.0% for CD among those who reduced their dosing frequency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab treatment persistence and safety in a 2-year data analysis of an extended access programme. Danese, S., Subramaniam, K., Van Zyl, J., et al.[2022]

Vedolizumab demonstrated significant efficacy in bio-naïve patients with ulcerative colitis (UC) and Crohn's disease (CD), with 63.9% of UC patients and 61.7% of CD patients achieving clinical remission by week 52.

Bio-naïve patients with UC experienced a lower risk of serious adverse events compared to those previously treated, indicating a favorable safety profile for vedolizumab in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab as the first line of biologic therapy for ulcerative colitis and Crohn's disease - a systematic review with meta-analysis. Attauabi, M., Madsen, GR., Bendtsen, F., et al.[2023]

In a study of 100 patients with moderate to severe ulcerative colitis, vedolizumab demonstrated effectiveness with a clinical response in 62% and clinical remission in 50% after 54 weeks of treatment, indicating it is a viable option for managing this condition.

Despite its effectiveness, 37% of patients who responded to treatment experienced a relapse within 26 weeks after discontinuation, highlighting the need for ongoing monitoring and potential additional therapies after stopping vedolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world outcomes of 54-week vedolizumab therapy and response durability after treatment discontinuation in ulcerative colitis: results from a multicenter prospective POLONEZ study. Eder, P., Kłopocka, M., Cichoż-Lach, H., et al.[2023]

In a systematic review of 10 real-world studies involving 395 patients with inflammatory bowel disease (IBD), approximately 50% achieved a clinical response after escalating vedolizumab maintenance dosing from every 8 weeks to every 4 weeks.

Clinical response rates varied between 40% to 73% across the studies, indicating that dose escalation can be an effective strategy for patients experiencing secondary loss of response or non-response to vedolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness of Vedolizumab Dose Escalation in Patients With Inflammatory Bowel Disease: A Systematic Literature Review. Patel, D., Martin, S., Luo, M., et al.[2023]

Vedolizumab is an effective treatment option for patients with moderately to severely active Crohn's disease and ulcerative colitis who have not responded to conventional therapies or anti-TNF treatments.

The article provides practical management insights for using vedolizumab, drawing from both published research and the authors' clinical experiences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Questions and answers about the management of Crohn's disease and ulcerative colitis with vedolizumab. Hinojosa Del Val, J., Barreiro-de Acosta, M.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Higher Trough Vedolizumab Concentrations During Maintenance Therapy are Associated With Corticosteroid-Free Remission in Inflammatory Bowel Disease. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Vedolizumab as Induction and Maintenance for Inflammatory Bowel Disease: 12-month Effectiveness and Safety. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Outcomes of Vedolizumab Therapy in Ulcerative Colitis and Crohn's Disease at a Tertiary Referral Center. [2018]

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

Long-term clinical experience with vedolizumab in patients with inflammatory bowel disease. [2022]

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

Vedolizumab and Anti-Tumour Necrosis Factor α Real-World Outcomes in Biologic-Naïve Inflammatory Bowel Disease Patients: Results from the EVOLVE Study. [2022]

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

Retrospective Analysis of Safety of Vedolizumab in Patients With Inflammatory Bowel Diseases. [2021]

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

Review of vedolizumab for the treatment of ulcerative colitis. [2020]

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

Vedolizumab: an α4β7 integrin inhibitor for inflammatory bowel diseases. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Vedolizumab treatment persistence and safety in a 2-year data analysis of an extended access programme. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Vedolizumab as the first line of biologic therapy for ulcerative colitis and Crohn's disease - a systematic review with meta-analysis. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Real-world outcomes of 54-week vedolizumab therapy and response durability after treatment discontinuation in ulcerative colitis: results from a multicenter prospective POLONEZ study. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness of Vedolizumab Dose Escalation in Patients With Inflammatory Bowel Disease: A Systematic Literature Review. [2023]

13. Spain pubmed.ncbi.nlm.nih.gov

Questions and answers about the management of Crohn's disease and ulcerative colitis with vedolizumab. [2020]