NCT03724929

Value of Pharmacokinetic Assays in the Prediction of Therapeutic Response in Ulcerative Colitis

Value of Pharmacokinetic Assays (Vedolizumab and Anti-vedolizumab Antibody) in the Prediction of Induction and Maintenance Therapeutic Response in Ulcerative Colitis

• Status: Terminated
• Phase: N/A
• Study type: Interventional
• Enrollment: 67 (actual)
• Sponsor: Centre Hospitalier Universitaire de Saint Etienne · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Vedolizumab (VDZ) is a monoclonal antibody that binds to the heterodimer α4β7 integrin and which has shown its efficacy in Ulcerative Colitis (UC) by inducing and maintaining clinical response/remission. The French marketing authorization was obtained for Ulcerative Colitis in patients in failure with anti-Tumor Necrosis Factor (anti-TNF) agents. In the pivotal study, correlation between drug levels and clinical response during induction and maintenance therapy were reported. Moreover, in 3.7% of cases, anti-vedolizumab antibodies were reported during the time-course and 1% had samples that were persistently positive. Up to now, data on the pharmacologic VDZ parameters are scarce and the relationships as well as the predictive value of the measurement of VDZ concentrations and VDZ monoclonal antibodies (mAbs) during the induction and maintenance phases remains unknown. It could be of paramount interest to early identify UC patients under VDZ who will be responders to VDZ induction and to identify those who will achieve clinical remission under maintenance therapy with VDZ.

Detailed description

The contribution of the pharmacokinetic studies of monoclonal antibodies (anti-TNF antibodies currently) has assumed increasing importance of its use in clinical practice. Therapeutic algorithms for both Infliximab (IFX) and Adalimumab (ADA) have been published and are used by many expert teams in the event of loss of therapeutic response. Similarly, the concentrations are assuming important in the indication of therapeutic de-escalation. Lastly, the assays may predict medium-term therapeutic response to treatment and thus enable proposal of preventive therapeutic changes (5). The Gemini 1 study (phase 3 vedolizumab vs. placebo in Ulcerative Colitis) showed a correlation between drug levels and clinical response during induction and maintenance therapy. Moreover, in 3.7% of cases, anti-vedolizumab antibodies were reported during the time-course and 1% had samples that were persistently positive. (1). In addition, we have decided to assess the clinical response to VDZ induction at W10 (Week 10), as the Gemini III trial for Crohn Disease (Crohn Disease) have reported, among patients who had experienced previous Tumor Necrosis Factor (TNF) antagonist failure, that 15% of those given vedolizumab versus 12% under placebo were in remission at W6 (P=0.433) whereas a higher proportion of them were in remission (26%) under VDZ when compared with the placebo arm (12%) at week 10. Therefore, in clinically non-responders at W10, an additional dose of 300 mg of VDZ will be infused at W10 and every four weeks.

Conditions

• Ulcerative Colitis

Interventions

Type	Name	Description
PROCEDURE	Blood sample	Blood samples will be systematically collected at W0, W2, W6, W14 and W52 for vedolizumab pharmacokinetic parameters, including the vedolizumab trough levels and the specific anti-vedolizumab antibody. A supplementary blood sample will be collected at W10 which is the point where a significant greater number of patients were in remission.
DEVICE	Rectosigmoidoscopy	Rectosigmoidoscopy will be performed in each center at time points W0, W10 and W52.

Timeline

• Start date: 2019-03-04
• Primary completion: 2022-04-15
• Completion: 2022-06-28
• First posted: 2018-10-30
• Last updated: 2023-05-23

Locations

5 sites across 1 country: France