Immunomodulator Strategy for Inflammatory Bowel Disease

(QUOTIENT Trial)

Recruiting in Palo Alto (17 mi)

+18 other locations

Overseen by Siddharth Singh, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of California, San Diego

Must be taking: Targeted immunomodulators

Disqualifiers: Ostomy, Ileoanal pouches, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare the effectiveness and safety of a strategy of switching to an alternative targeted immunomodulator (TIM) therapy to treat to a target of endoscopic remission, versus continuing index TIM in patients with inflammatory bowel disease (IBD) (Crohn's disease or ulcerative colitis \[UC\]) in symptomatic remission with moderate to severe endoscopic inflammation despite optimization of index TIM in a real-world setting.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that your current treatment with a targeted immunomodulator (TIM) is stable for at least 3 months before certain procedures. You may need to switch to a different TIM if you qualify for the study.

What data supports the effectiveness of the drug Vedolizumab (Entyvio) for treating inflammatory bowel disease?

Vedolizumab has been shown to be effective and safe for treating moderate to severe Crohn's disease and ulcerative colitis, with clinical trials indicating higher rates of clinical response and remission compared to placebo. It works by blocking specific immune cells from reaching the gut, reducing inflammation. ^{1 2 3 4 5}

Is vedolizumab safe for humans?

Vedolizumab (also known as Entyvio) has been shown to be generally safe in clinical trials for treating inflammatory bowel diseases like Crohn's disease and ulcerative colitis. It is well tolerated and has a low risk of serious infections, making it a safe option for many patients. ^{1 2 3 4 5}

How is the drug vedolizumab different from other treatments for inflammatory bowel disease?

Vedolizumab is unique because it specifically targets the α4β7 integrin, which helps control the movement of immune cells into the gut, reducing inflammation. Unlike other treatments that block tumor necrosis factor (TNF), vedolizumab is gut-specific, which may lower the risk of certain side effects, such as progressive multifocal leukoencephalopathy, seen with less selective treatments. ^{2 3 5 6 7}

Research Team

Siddharth Singh, MD

Principal Investigator

UC San Diego Health

Eligibility Criteria

Adults aged 18-80 with Crohn's Disease or Ulcerative Colitis, currently in symptomatic remission but still showing moderate to severe inflammation. They must be on a stable dose of an optimized targeted immunomodulator (TIM) therapy and not pregnant or breastfeeding. Excluded are those with ostomies, prior study enrollment, mild disease activity, serious non-IBD diseases, or substance abuse issues.

Inclusion Criteria

I can be treated with at least one other approved medication for my condition.

I am currently on medication for IBD, including biologics or small molecule inhibitors.

I have had tests showing severe bowel inflammation in the last 3 months.

Exclusion Criteria

Mild endoscopic disease activity, where treating providers would not consider switching TIM

I don't have a serious illness that could stop me from fully participating in the study.

Presence of ostomy or ileoanal pouches

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either switch to an alternative TIM or continue with the index TIM for the treatment of IBD

104 weeks

Visits follow local standard of care with additional visits at physician's discretion

Follow-up

Participants are monitored for safety and effectiveness after treatment

104 weeks

Data collection every 6 months, PRO measures every 12 weeks

Treatment Details

Interventions

• Pragmatic (Other)

Trial Overview The trial is testing whether switching to a different TIM therapy leads to endoscopic remission versus continuing the current TIM for IBD patients who are symptom-free but have significant inflammation. It will take place in a real-world setting and compare the effectiveness and safety of these strategies.

Participant Groups

Group I: Switching Targeted Immunomodulators Treatment Experimental Treatment 1 Intervention

Participants randomized to a strategy of switching TIM will be switched to one of the preferred agents recommended by clinical guidelines and covered by the participants' insurance formulary as part of routine care, and at the discretion of the site investigator and treating provider. No study-related medications will be provided. For participants randomized to switch to an alternative TIM, selection of alternative agent will be determined at the discretion of the local site physician in accordance with clinical guidelines on the management of moderate to severe ulcerative colitis, and management of moderate to severe CD from the AGA and ACG.9, 34, 35 These guidelines include recommendations on positioning of TIMs for first line use (TIM-naïve patients) and second-line use (in patients with prior exposure to TIMs).

Group II: Continuing Index Targeted Immunomodulators Treatment Experimental Treatment 1 Intervention

Participants randomized to a strategy of continuing TIM will continue on their concomitant therapy.

Pragmatic is already approved in Canada for the following indications:

Approved in Canada as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Dr. Christopher Longhurst

University of California, San Diego

Chief Medical Officer since 2021

MD and MS in Medical Informatics from UC Davis

Patty Maysent

University of California, San Diego

Chief Executive Officer since 2016

MBA from Stanford University

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

Paul Klotman

Baylor College of Medicine

Chief Executive Officer since 2010

MD, PhD

James Versalovic

Baylor College of Medicine

Chief Medical Officer since 2020

MD from Baylor College of Medicine

Crohn's and Colitis Foundation

Collaborator

Trials

44

Recruited

27,500+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Nakela L. Cook

Patient-Centered Outcomes Research Institute

Chief Executive Officer since 2020

MD, MPH

Harv Feldman

Patient-Centered Outcomes Research Institute

Chief Medical Officer

MD, MSCE

Western University

Collaborator

Trials

31

Recruited

129,000+

Findings from Research

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]

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 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]

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 a novel biologic therapy that targets the α4β7 integrin, which plays a crucial role in the recruitment of leukocytes to inflamed gut tissue, offering a new approach for treating Crohn's disease and ulcerative colitis.

Clinical trial results indicate that vedolizumab may provide an effective treatment option for patients who do not respond to existing therapies that block tumor necrosis factor alpha, addressing a significant unmet need in managing inflammatory bowel diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Designing biologic selectivity for inflammatory bowel disease--role of vedolizumab. Krupka, N., Baumgart, DC.[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]

References

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

An update on the safety of long-term vedolizumab use in inflammatory bowel disease. [2023]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Low Frequency of Opportunistic Infections in Patients Receiving Vedolizumab in Clinical Trials and Post-Marketing Setting. [2023]

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

Vedolizumab: first global approval. [2021]

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

Vedolizumab as a Treatment for Crohn's Disease and Ulcerative Colitis. [2022]

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

Designing biologic selectivity for inflammatory bowel disease--role of vedolizumab. [2022]

7. 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]