NCT04797325

Vedolizumab for Immune Mediated Colitis

Open Label Randomized Controlled Clinical Trial of Vedolizumab Versus Conventional Treatment for Checkpoint Inhibitor Induced Colitis

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 82 (estimated)
• Sponsor: University of Copenhagen · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open label randomized trial to evaluate the efficacy and treatment duration with vedolizumab to patients with immune mediated colitis. The trial will include 82 patients randomized into two arms, either standard treatment with prednisolone (plus infliximab in severe cases) or vedolizumab treatment up front.

Detailed description

Background information Immune check point inhibitors (ICPI) have revolutionized the treatment of a growing number of cancer forms resulting in a rapidly increasing number of patients treated with these drugs within the very recent years. The aim is to allow and boost an immune response towards the neoantigens of neoplastic cells, but the blockage of inhibitory signals might also interfere with normal barriers against the development of autoimmunity or autoimmune-like reactions and thus lead to a number of immune-related adverse events (IrAEs). Gastrointestinal inflammation - typically colitis - is the most common IrAE among ICPI treated patients. Vedolizumab, a integrin antibody, has been shown to be highly effective in treating ICPI induced colitis with remission rates of 85%. Vedolizumab has a better safety profile than anti-tumor necrosis factor antibodies, including infliximab, with lower risk of infections and tumor development in inflammatory bowel disease patients. Moreover, vedolizumab does not seem to inhibit tumor specific T cell responses in vitro, suggesting that this treatment is also beneficial with regards to tumor response. The hypothesis Vedolizumab induction and maintenance treatment of patients with ICPI related intestinal symptoms and evidence of colitis: 1. Is effective in inducing remission of the colitis 2. Reduces the risk of progression from grade 2 to grade 3 or 4 colitis 3. Reduces the need of systemic corticosteroid 4. Is not associated with increased risk of tumor progression or other serious adverse events including serious infections 5. Allows reintroduction/continuation of ICPI treatment. Further it is hypothesized that ICPI induced colitis can be diagnosed and monitored by intestinal bowel ultrasound and treatment response is associated with multi-omics changes in intestinal tissue, tumor tissue, feces, blood, and urine, e.g. peripheral blood mononuclear cells (PBMCs) RNAseq profiles, profiles of single cell RNAseq from isolated immune cells from standard pinch biopsies from the inflamed colon and composition of the microbiota. Lastly, it is hypothesized, that anti-tumor T-cell function is affected in vivo by the medication used to treat ICPI induced colitis, and that this can be assessed by changes in single cell RNAseq profiles of tumor resident T-cells (isolated from tumor biopsies).

Conditions

• Immune-Mediated Colitis

Interventions

Type	Name	Description
DRUG	Vedolizumab	Repeatedly vedolizumab infusion at week 0, 2, 6, 14, 22
DRUG	Prednisolone	tablet prednisolone plus infliximab in severe cases.

Timeline

• Start date: 2021-08-30
• Primary completion: 2025-04-01
• Completion: 2025-04-01
• First posted: 2021-03-15
• Last updated: 2022-08-17

Locations

1 site across 1 country: Denmark