Vedolizumab for Colitis

(EVITA Trial)

Overseen By Shilpa Grover, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Shilpa Grover, MD, MPH

Must not be taking: Immunosuppressive biologics, Systemic steroids

Disqualifiers: Colonic infection, Hepatitis B/C, Tuberculosis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

80 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to compare the effectiveness and safety of Vedolizumab with a short course of steroids compared to standard course of steroids for the treatment of immune checkpoint inhibitor colitis (ICI colitis) in adults. The main questions it aims to answer are: * How many patients treated with Vedolizumab and a short course of steroids experience resolution of colitis at 8 weeks. * How many patients treated with a standard course of steroids experience resolution of colitis at 8 weeks. Participants will: Recieve 3 doses of Vedolizumab or a placebo (a look-alike substance that contains no drug) infusions over 6 weeks Receive intravenous Medrol daily for 3 days Receive Prednisone daily for 7 days Receive Prednisone or placebo taper daily Receive Sulfamethoxazole-Trimethoprim or placebo taper daily Weekly checkups and periodic tests

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but it excludes those who have used immunosuppressive biologic medications recently or need systemic steroids for other conditions. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Vedolizumab for colitis?

Research shows that Vedolizumab is effective in helping patients with ulcerative colitis, a type of inflammatory bowel disease, achieve and maintain remission (a period without symptoms). It is often used when other treatments have not worked, and studies have shown it to be safe and effective in real-world settings. ^{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. ^{1 2 6 7 8}

How is the drug Vedolizumab unique for treating colitis?

Vedolizumab is unique because it is a gut-selective treatment that specifically targets the immune cells involved in inflammation in the intestines, making it different from other treatments that affect the entire immune system. It is used when conventional therapies fail and can be a first-line or second-line biological treatment option. ^{1 3 9 10 11}

Research Team

Shilpa Grover, MD, MPH

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for adults with immune-related colitis, specifically from cytomegalovirus or general colitis. Participants must be experiencing colitis due to immune checkpoint inhibitors and are able to receive various treatments including steroids and Vedolizumab.

Inclusion Criteria

Willing and able to comply with the requirements of the protocol

Ability to understand and the willingness to sign a written informed consent document

My colitis was confirmed through a scope and tissue test.

Exclusion Criteria

Allergy to sulfamethoxazole-trimethoprim

I currently have an infection in my colon.

Unable to adhere to protocol requirements

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Vedolizumab infusions (3 doses) and steroids for 10 days, with weekly checkups and periodic tests

8 weeks

Weekly checkups (in-person or phone)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with medical records reviewed at 12 months

12 months

Treatment Details

Interventions

• Vedolizumab

Trial Overview The trial tests if Vedolizumab plus a short steroid course is more effective than just steroids in treating colitis at 8 weeks. Patients will get either Vedolizumab or placebo infusions, along with initial intravenous Medrol, followed by Prednisone and its tapering doses, as well as Sulfamethoxazole-Trimethoprim or its placebo.

Participant Groups

Group I: Vedolizumab and Short Course of Steroids Experimental Treatment 4 Interventions

Participants in this arm will receive Vedolizumab infusions (3 doses) and steroids for 10 days (intravenous Medrol daily for 3 days and Prednisone daily for 7 days). Participants may also receive daily placebo (for Prednisone and Sulfamethoxazole-Trimethoprim).

Group II: Standard Course of Steroids Active Control 4 Interventions

Participants in this arm will receive steroids for 10 days (intravenous Medrol daily for 3 days and Prednisone daily for 7 days), followed by a steroid (Prednisone) taper. Participants may also receive Sulfamethoxazole-Trimethoprim (an antibiotic). Participants will receive 3 placebo infusions.

Who Is Running the Clinical Trial?

Shilpa Grover, MD, MPH

Lead Sponsor

Trials

1

Recruited

80+

Takeda

Industry 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

Dana-Farber/Brigham and Women's Cancer Center

Collaborator

Trials

7

Recruited

3,500+

Findings from Research

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]

In a study of 100 ulcerative colitis patients, vedolizumab induction therapy resulted in an 83% clinical response rate and 62% mucosal healing at week 14, demonstrating its effectiveness in real-world settings.

The treatment was found to be safe, with no new safety concerns reported and no patients discontinuing due to adverse events, indicating a favorable safety profile for vedolizumab in patients with severe UC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness and safety of vedolizumab induction therapy for ulcerative colitis: A prospective nationwide Polish observational study. Zagórowicz, E., Cichoż-Lach, H., Kopertowska-Majchrzak, M., et al.[2023]

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]

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 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 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]

References

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

Vedolizumab for induction and maintenance of remission in ulcerative colitis: a Cochrane systematic review and meta-analysis. [2018]

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

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

3. Poland pubmed.ncbi.nlm.nih.gov

Real-world effectiveness and safety of vedolizumab induction therapy for ulcerative colitis: A prospective nationwide Polish observational study. [2023]

4. 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]

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

Transcriptional Behavior of Regulatory T Cells Predicts IBD Patient Responses to Vedolizumab Therapy. [2022]

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

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

7. England pubmed.ncbi.nlm.nih.gov

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

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

Predicting corticosteroid-free endoscopic remission with vedolizumab in ulcerative colitis. [2022]

10. 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]

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

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