Vedolizumab for Colitis

(EVITA Trial)

Recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to treat colitis caused by cancer treatments. Researchers aim to determine if Vedolizumab, a biologic medication, combined with a short course of steroids, can more effectively clear up colitis in adults compared to the usual longer course of steroids. Participants will receive either Vedolizumab with a short course of steroids or the standard steroid treatment alone. The trial seeks adults who have confirmed ICI colitis, experienced moderate to severe diarrhea, and recently received cancer treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Studies have shown that Vedolizumab is generally safe for long-term use. In one study, serious side effects occurred at a rate of 1.2 per 100 patient-years, indicating they are relatively rare. Another report found that out of over 32,000 patients, 10% experienced serious side effects when treated for ulcerative colitis and 14% for Crohn's disease. Most of these side effects related to the patients' existing conditions rather than the medication itself.

In one large study, there were 18 deaths, but only one was linked to the treatment. The others resulted from different causes, such as pneumonia. Overall, research indicates that Vedolizumab is well-tolerated, meaning most people do not experience major problems when taking it. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colitis?

Researchers are excited about Vedolizumab for colitis because it targets a specific protein called integrin, which plays a key role in the inflammation process of the gut. Unlike traditional treatments that broadly suppress the immune system, Vedolizumab offers a more targeted approach, potentially reducing side effects. Additionally, while steroids like Prednisone are commonly used and effective, they can have significant long-term side effects. Vedolizumab, on the other hand, promises a targeted mechanism that may offer a safer long-term option for patients with colitis.

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

Research has shown that Vedolizumab can effectively treat colitis, particularly ulcerative colitis. One study found that 42% of patients were symptom-free after using Vedolizumab. Another study reported that 62% of patients showed improvement after 54 weeks of treatment. Additionally, Vedolizumab may outperform some other treatments, with 82.3% of patients being symptom-free after a year. In this trial, one group of participants will receive Vedolizumab with a short course of steroids, while another group will receive a standard course of steroids. These findings suggest that Vedolizumab has strong potential to relieve colitis symptoms. ^{6 7 8 9 10}

Who Is on the Research Team?

Shilpa Grover, MD, MPH

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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 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 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]

Citations

1. 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), ...

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/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 ...

4. gastroenterologyadvisor.com gastroenterologyadvisor.com/reports/vedolizumab-for-ulcerative-colitis-superior-to-infliximab-as-first-line-therapy/

Vedolizumab for Ulcerative Colitis May Be Superior to ... At week 52, vedolizumab and infliximab recipients exhibited clinical remission rates of 82.3% and 77.4% (P =.11), endoscopic remission rates of ...

5. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1188751/full

Effectiveness and safety of vedolizumab for ulcerative colitis In terms of long-term efficacy, the GEMINI LTS trial showed a clinical remission rate of 88% in patients who responded to induction therapy ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11289824/

Long-term outcomes and predictors of vedolizumab ... The rate of serious adverse events was 1.2 per 100 patient-years of follow-up. Conclusion: VDZ effectiveness appears enduring with favourable ...

7. cghjournal.org cghjournal.org/article/S1542-3565(25)00891-2/fulltext

Long-Term Safety of Vedolizumab in Patients With ... Deaths. There were 18 deaths in the vedolizumab group, 1 of which was considered treatment-related and was due to pneumonia. · Neoplasms. Benign ...

8. academic.oup.com academic.oup.com/ecco-jcc/article/18/Supplement_1/i1900/7587069

P1062 Effectiveness and safety outcomes beyond five years of ... About one-third of pts were still receiving VDZ after a fup of more than 6 years, with the majority of them being in clinical remission and more ...

9. tandfonline.com tandfonline.com/doi/full/10.1080/14740338.2023.2247976

An update on the safety of long-term vedolizumab use in ... With 208,050 PYs of vedolizumab exposure in 32,752 patients, there were 3580 (10%) SAEs reported for UC and 5230 (14%) SAEs for CD. SAEs related to active IBD, ...

10. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2796853

Comparative Outcomes and Safety of Vedolizumab vs ... This study suggests that vedolizumab is associated with a higher risk of treatment failure compared with TNF antagonists, without offering any safety advantage ...