Immunomodulator Strategy for Inflammatory Bowel Disease

(QUOTIENT Trial)

Recruiting at 19 trial locations

Overseen By Jason Hou, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Diego

Must be taking: Targeted immunomodulators

Disqualifiers: Ostomy, Ileoanal pouches, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 104 weeks

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of different immunomodulator therapies for individuals with inflammatory bowel disease (IBD), such as Crohn's disease or ulcerative colitis. The researchers aim to determine if switching to a new therapy yields better results than continuing with the current one, particularly when inflammation persists. Individuals diagnosed with IBD for at least six months, who are on a stable treatment plan but still experience moderate to severe inflammation, might be suitable candidates. Participants will either continue their current treatment or switch to a new one, based on their doctor's recommendation. One of the therapies under study is Pragmatic (also known as Entyvio or Vedolizumab). As an unphased trial, this study provides a unique opportunity to explore new treatment options and contribute to advancing IBD care.

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.

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

Research has shown that treatments like vedolizumab, used for Crohn's disease and ulcerative colitis, are generally safe. Studies involving over 3,300 adults indicate that vedolizumab typically causes only mild side effects, which align with expectations from earlier research. Importantly, no new safety issues have emerged even with long-term use. Therefore, for those considering joining a trial with this treatment, evidence suggests it is generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial for inflammatory bowel disease (IBD) because it explores two strategic approaches for using targeted immunomodulators (TIMs). Unlike conventional treatments that often stick to a single immunomodulator, this trial investigates the benefits of switching TIMs versus continuing the current therapy. This approach could reveal insights into optimizing treatment plans based on individual patient responses, potentially leading to more personalized and effective care strategies for conditions like ulcerative colitis and Crohn's disease. By aligning treatment choices with clinical guidelines and insurance coverage, the trial also aims to improve accessibility and adherence to effective therapies.

What evidence suggests that this trial's treatments could be effective for inflammatory bowel disease?

Research has shown that certain medications, such as vedolizumab, effectively treat inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Studies have found that vedolizumab can provide long-term relief. One study found that half of the patients felt better within a year after increasing the frequency of vedolizumab administration. Another study demonstrated that vedolizumab remained effective for two years. In this trial, participants may either continue their current targeted immunomodulator treatment or switch to an alternative, based on clinical guidelines and their healthcare provider's discretion. These findings suggest that starting or continuing treatment with a medication like vedolizumab can help manage IBD symptoms. ^{1 6 7 8 9}

Who Is on the Research Team?

Siddharth Singh, MD

Principal Investigator

UC San Diego Health

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Pragmatic

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.

How Is the Trial Designed?

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 European Union, United States, Canada for the following indications:

Approved in European Union as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Approved in United States as Entyvio for:

• Moderate to severe ulcerative colitis
• Moderate to severe Crohn's disease

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+

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

Crohn's and Colitis Foundation

Collaborator

Trials

44

Recruited

27,500+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Western University

Collaborator

Trials

31

Recruited

129,000+

Published Research Related to This Trial

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 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]

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]

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8255566/

Real-world effectiveness of vedolizumab in inflammatory ... We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD).

2. entyviohcp.com entyviohcp.com/ulcerative-colitis-efficacy

Demonstrated efficacy in ulcerative colitis Demonstrated efficacy in ulcerative colitis · Lasting relief and CS-free remission at Week 521* · Individual results may vary. · *Many patients taking ENTYVIO IV ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1590865825007364

Vedolizumab in inflammatory bowel disease: Real-world ... In this study, we investigated the 2-year effectiveness and safety of vedolizumab in patients with IBD, and applied eXplainable Artificial Intelligence (XAI) to ...

4. entyvio.com entyvio.com/

ENTYVIO® (vedolizumab) for Crohn's Disease or Ulcerative ... ENTYVIO is a biologic treatment for moderate to severe Crohn's disease (CD) or ulcerative colitis (UC). See Safety and Prescribing Information.

5. academic.oup.com academic.oup.com/crohnscolitis360/article/4/3/otac020/6634003

Real-World Effectiveness of Vedolizumab Dose Escalation in ... Our findings showed that 1 in 2 people had improved outcomes within a year of increased vedolizumab dosing frequency. Introduction. Inflammatory ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31504340/

The Safety Profile of Vedolizumab in Ulcerative Colitis and ... Adverse event patterns were consistent with clinical trials, with no new safety concerns. Most reported events were non-serious and event ...

7. entyviohcp.com entyviohcp.com/safety-profile

Safety Profile for ENTYVIO® (vedolizumab) Up to 7 years of consistent results across safety parameters. 1-3 * Clinical trials evaluated safety in more than 3300 adults (UC, Crohn's, and healthy ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37610086/

An update on the safety of long-term vedolizumab use in ... Vedolizumab is an effective therapy for inflammatory bowel disease with a well-established safety profile. No unexpected long-term safety signals have been ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT00783718

NCT00783718 | Study of Vedolizumab (MLN0002) in ... This multicenter, phase 3, randomized, blinded, placebo-controlled study in patients with moderately to severely active ulcerative colitis comprises two phases.