Vedolizumab for Gastritis

Overseen By Keri Sullivan

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Disqualifiers: Allergy to vedolizumab, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What evidence supports the effectiveness of the drug Vedolizumab (Entyvio) for treating gastritis?

Vedolizumab (Entyvio) has been shown to be effective in treating inflammatory bowel diseases like Crohn's disease and ulcerative colitis by reducing gut inflammation. While there is no direct evidence for its use in gastritis, its ability to target gut-specific inflammation suggests it might help with similar conditions. ^{1 2 3 4 5}

Is Vedolizumab generally safe for humans?

Vedolizumab, also known as Entyvio, has been studied for safety in treating inflammatory bowel diseases like Crohn's disease and ulcerative colitis. It has a low frequency of serious infections and no significant developmental toxicity in animal studies. However, some adverse events have been reported, and longer-term studies are needed to fully understand its safety profile. ^{1 2 4 6 7}

How is the drug Vedolizumab different from other treatments for gastritis?

Vedolizumab is unique because it is a biologic drug that targets specific immune cells to reduce inflammation, unlike other treatments for gastritis that typically focus on reducing stomach acid or eradicating bacteria like Helicobacter pylori. ^{8 9 10 11 12}

What is the purpose of this trial?

The goal of this clinical trial is to learn about how vedolizumab may affect patients with collagenous gastritis (CG). The main questions it aims to answer are: * Whether vedolizumab can reduce CG symptoms * Whether vedolizumab is safe to take for patients with CG Participants in this study will: * Receive vedolizumab through an IV ("infusion") * Complete a survey at each infusion visit * Have blood collected at each infusion visit * Undergo an endoscopy with biopsy at 2 timepoints

Eligibility Criteria

This trial is for individuals with collagenous gastritis, a stomach condition causing inflammation and discomfort. Participants will receive vedolizumab infusions, complete surveys, provide blood samples, and undergo endoscopy with biopsy to monitor effects.

Inclusion Criteria

I am 14 years old or older.

I weigh at least 40kg.

My diagnosis of collagenous gastritis is confirmed by a biopsy.

Exclusion Criteria

I cannot give consent on my own due to my condition.

Allergic to vedolizumab or any of its components

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Initial Treatment

Participants receive vedolizumab infusions at weeks 0, 2, and 6

6 weeks

3 visits (in-person)

Extended Treatment

Participants who respond well continue to receive vedolizumab every 8 weeks for about 1 year

48 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Vedolizumab

Trial Overview The study tests whether vedolizumab can alleviate symptoms of collagenous gastritis and assesses its safety. Vedolizumab is administered intravenously during the trial period while participants' health responses are closely monitored.

Participant Groups

Group I: Vedolizumab 300mg Experimental Treatment 1 Intervention

* Dose: 300mg * Administration: Intravenous (IV) * Frequency: Weeks 0, 2, 6, and then every 8 weeks * Duration: 54 weeks (1 year)

Vedolizumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Approved in United States as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Approved in Canada as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Approved in Japan as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

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

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 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]

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 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, a monoclonal antibody used for treating ulcerative colitis and Crohn's disease, showed no adverse effects on maternal health or fetal development in pregnant rabbits and cynomolgus monkeys during preclinical toxicity studies.

In both animal models, vedolizumab did not increase the risk of prenatal loss or stillbirth, and there were no negative impacts on infant development or health, indicating its safety for use during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Developmental Toxicity of Vedolizumab, an α4β7 Receptor Antagonist, in Rabbit and Nonhuman Primate. Crawford, D., Friedman, M.[2020]

Vedolizumab, a gut-selective integrin blocker for Crohn's disease and ulcerative colitis, showed a similar rate of serious adverse events (35.9%) compared to anti-TNF drugs (32.1%) in a study analyzing 499 reports for vedolizumab and 119,620 for anti-TNFs.

The study identified 22 groups of adverse events associated with vedolizumab, including 9 with serious outcomes, suggesting potential cardiovascular risks; however, these findings are preliminary and require further investigation through long-term studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the real-world safety profile of vedolizumab using the United States Food and Drug Administration adverse event reporting system. Cross, RK., Chiorean, M., Vekeman, F., et al.[2023]

In a double-blind study of 52 patients with confirmed gastritis, those treated with 300 mg of ranitidine daily for four weeks showed significant improvement, with 80% of patients experiencing complete symptom resolution compared to only 45% in the placebo group.

Ranitidine was found to be an effective short-term treatment for gastritis, with no significant adverse effects reported, confirming its safety and efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical investigation of ranitidine in patients with gastritis. Hadi, S.[2013]

In a study of 147 treatment-naïve patients with Helicobacter pylori, the eradication rate of vonoprazan-based triple therapy (V-AC) in those with clarithromycin-susceptible infections was found to be 87.3%, which is below the ideal target of 90%.

The V-AC regimen was effective in eradicating 82.9% of clarithromycin-resistant infections, suggesting that with adjustments in dosage or treatment duration, V-AC could be a promising option for resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vonoprazan- vs proton-pump inhibitor-based first-line 7-day triple therapy for clarithromycin-susceptible Helicobacter pylori: A multicenter, prospective, randomized trial. Sue, S., Ogushi, M., Arima, I., et al.[2022]

In a study of 372 patients with chronic antral gastritis, diffuse gastritis, and ulcer disease, the addition of immunomodulators tactivin and levamisol to standard treatment led to faster healing of lesions, with an average healing time of 18.4 days compared to 24.3 days for standard treatment alone.

The use of levamisol not only improved healing times but also reduced the number of recurrences in patients with chronic gastritis and ulcer disease, suggesting it enhances the overall efficacy of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness of using immunomodulators in combined treatment of patients with chronic gastritis and ulcer disease]. Arutiunian, VM., Grigorian, EG.[2016]

DA-9601 demonstrated significantly higher endoscopic cure rates for erosive gastritis compared to cetraxate, with cure rates of 56% and 58% for DA-9601 (180 mg and 360 mg) versus 36% for cetraxate in the per protocol analysis.

Both DA-9601 and cetraxate were found to be safe, with no treatment-associated adverse events reported during the 2-week study involving 512 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DA-9601 for erosive gastritis: results of a double-blind placebo-controlled phase III clinical trial. Seol, SY., Kim, MH., Ryu, JS., et al.[2019]

In a study of 2507 patients, vonoprazan combined with antibiotics showed a significantly higher success rate for primary eradication of Helicobacter pylori compared to the traditional proton pump inhibitor (PPI) regimen, especially in patients with chronic gastritis.

The eradication rates for secondary treatment were similar between the vonoprazan and PPI groups, suggesting that while vonoprazan is effective for initial treatment, it may not offer additional benefits for patients who have previously failed treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usefulness of vonoprazan, a potassium ion-competitive acid blocker, for primary eradication of Helicobacter pylori. Yamada, S., Kawakami, T., Nakatsugawa, Y., et al.[2020]

References

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

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

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

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

3. 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]

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

Evaluation of the Developmental Toxicity of Vedolizumab, an α4β7 Receptor Antagonist, in Rabbit and Nonhuman Primate. [2020]

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

Assessment of the real-world safety profile of vedolizumab using the United States Food and Drug Administration adverse event reporting system. [2023]

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

Clinical investigation of ranitidine in patients with gastritis. [2013]

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

Vonoprazan- vs proton-pump inhibitor-based first-line 7-day triple therapy for clarithromycin-susceptible Helicobacter pylori: A multicenter, prospective, randomized trial. [2022]

10. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Effectiveness of using immunomodulators in combined treatment of patients with chronic gastritis and ulcer disease]. [2016]

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

DA-9601 for erosive gastritis: results of a double-blind placebo-controlled phase III clinical trial. [2019]

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

Usefulness of vonoprazan, a potassium ion-competitive acid blocker, for primary eradication of Helicobacter pylori. [2020]