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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-001587-11 | EudraCT Number |
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low inclusion rates
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| Name | Class |
|---|---|
| Theradiag | OTHER |
| Takeda | INDUSTRY |
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Vedolizumab (VDZ) is a monoclonal antibody which has shown its efficacy in Crohn's disease by inducing and maintaining clinical response/remission. The French marketing authorization was obtained for Crohn's disease in patients in failure with anti-TNF (Tumor Necrosis Factor) agents.
For Crohn's disease patients treated with vedolizumab, a strong association between vedolizumab serum levels and clinical response to induction and maintenance was demonstrated by anterior studies.
It could be of paramount interest to early identify Crohn's Disease patients under vedolizumab who will be responders to vedolizumab induction and to identify those who will achieve clinical remission under maintenance therapy with vedolizumab.
Researchers decided to assess the clinical response to vedolizumab induction at week 10. For clinically non-responders at week 10, an additional dose of 300 mg of vedolizumab will be infused at week 10 and then every four weeks.
Vedolizumab (VDZ) is a monoclonal antibody that binds to the heterodimer alpha 4 beta 7 integrin and which has shown its efficacy in Crohn's disease by inducing and maintaining clinical response/remission. The French marketing authorization was obtained for Crohn's disease in patients in failure with anti-TNF (Tumor Necrosis Factor) agents.
For Crohn's disease patients treated with vedolizumab, a strong association between vedolizumab serum levels and clinical response to induction and maintenance was demonstrated by anterior studies.
It could be of paramount interest to early identify Crohn's Disease patients under vedolizumab who will be responders to vedolizumab induction and to identify those who will achieve clinical remission under maintenance therapy with vedolizumab.
Researchers decided to assess the clinical response to vedolizumab induction at week 10, as the Gemini III trial has reported, among patients who had experienced previous TNF (Tumor Necrosis Factor) antagonist failure. 15% of those given vedolizumab were in remission at week 6 (P=0.433) versus 12% under placebo. At week 10, 26% under vedolizumab were in remission versus 12% in the placebo arm.
Moreover, at week 10, the proportion of patients presenting a clinical response was significantly higher in Crohn's Disease patients treated with vedolizumab (46% vs 24%).
In this study, for clinically non-responders at week 10, an additional dose of 300 mg of vedolizumab will be infused at week 10 and then every four weeks. In a post hoc analysis of GEMINI 2, additional dose of vedolizumab in patients clinically non responders to vedolizumab obtained a clinical remission in 33% of case.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Crohn's disease patients | Experimental | The patients will receive vedolizumab in compliance with the marketing authorization regimen (300 mg at weeks 0, 2, 6 and then every 8 weeks) in Crohn's Disease patients in clinical failure or intolerant to anti-TNF (Tumor Necrosis Factor) drugs. In case of lack of clinical response at week 10 or loss of response in the follow-up, all patients will be optimized with vedolizumab 300 mg at week 10 (additional infusion) and every following 4 weeks in contrast with responder patients at week 10 who will not have vedolizumab infusion at this time-point but will receive the next vedolizumab infusion at week 14 and then every 8 weeks, as recommended. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vedolizumab | Drug | During each 8 visits (screening, V0, V1, V2, V3, V4, V5, V6) at weeks-1, 0, 2, 6, 10, 14, 22, 54, respectively), the following parameters will be systematically recorded: Crohn's disease Activity Index (CDAI), adverse events. Blood and fecal samples will be systematically collected at weeks 0, 2, 6, 10, 14, 22 and 54 for routine serum ultrasensitive CRP (C-Reactive Protein) and fecal calprotectin assessments and for vedolizumab pharmacokinetic parameters, including the vedolizumab trough levels and the specific anti-Vedolizumab antibodies. In case of loss of response, an additional measurement of serum CRP (C-Reactive Protein), fecal calprotectin and Vedolizumab pharmacologic parameters will be performed. |
| Measure | Description | Time Frame |
|---|---|---|
| Vedolizumab concentration at week 6 | The primary objective is to determine the optimal threshold of Vedolizumab serum concentration measured at week 6 capable to predict the clinical response at week 10 with Vedolizumab. | Week 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Vedolizumab concentration at week 14 | Determine the optimal threshold of Vedolizumab serum concentration measured at week 14 capable to predict the clinical remission at week 54 with Vedolizumab. | Week 14 |
| Concentration of Vedolizumab at week 2 |
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Inclusion Criteria :
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Xavier Roblin, MD | Centre Hospitalier Universitaire de Saint Etienne | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Kremlin Bicetre | Paris | Le Kremlin-Bicêtre | 94270 | France | ||
| CHU d'Amiens |
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| ID | Term |
|---|---|
| D003424 | Crohn Disease |
| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C543529 | vedolizumab |
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Investigating whether the Vedolizumab concentrations measured at week 2 are predictive of a clinical response and clinical remission at week 10.
| Week 2 |
| Presence of specific antibodies (anti-integrins) at week 2 | Investigating whether the presence of specific antibodies (anti-integrins) measured at week 2 are predictive of a clinical response and clinical remission at week 10. | Week 2 |
| Concentration of Vedolizumab at week 14 | Investigating whether the Vedolizumab concentrations measured at week 14 are predictive of a clinical response and clinical remission at week 54. | Week 14 |
| Presence of specific antibodies (anti-integrins) at week 14 | Investigating whether the presence of specific antibodies (anti-integrins) measured at week 14 are predictive of a clinical response and clinical remission at week 54. | Week 14 |
| Vedolizumab and calprotectin levels at week 2 | Analyzing the value of Vedolizumab trough levels measured at week 2 to predict a subsequent normalization of fecal calprotectin levels (< 250 micro grams/gram of stools) at week 10 under induction therapy with Vedolizumab in Crohn's Disease. | Week 2 |
| Vedolizumab and calprotectin levels at week 14 | Analyzing the value of Vedolizumab trough levels measured at week 14 to predict a subsequent normalization of fecal calprotectin levels (< 250 micro grams/gram of stools) at week 54 under maintenance therapy with Vedolizumab in Crohn's Disease. | Week 14 |
| Intra and inter-individual heterogeneity of Vedolizumab levels | Investigating the intra and inter-individual heterogeneity of Vedolizumab levels within the time-course of Vedolizumab therapy, including the induction and maintenance phases. The dosage of Vedolizumab in patients blood will be used. | Week 54 |
| Proportion of loss of clinical response | Comparing the proportion of loss of clinical response in responder Crohn's Disease patients as well as in primary non-responders requiring Vedolizumab dose-intensification within one-year of follow-up. | Week 54 |
| Vedolizumab serum levels | Comparing the Vedolizumab serum levels prior and after Vedolizumab optimization in primary non-responder patients or experiencing a loss of response (secondary non-response) requiring additional infusions of Vedolizumab. | Week 54 |
| Concentration of Vedolizumab at week 54 | Comparing the level of Vedolizumab between patients achieving a clinical remission or not at week 54. | Week 54 |
| Specific antibodies (anti-integrins) level at week 54 | Comparing the specific antibodies (anti-integrins) levels between patients achieving a clinical remission or not at week 54. | Week 54 |
| Amiens |
| 80000 |
| France |
| CHU L'Archet | Nice | 06200 | France |
| CHU Lyon-Sud, Hospices Civils de Lyon, PIERRE-BENITE | Pierre-Bénite | 69230 | France |
| Chu Saint Etienne | Saint-Etienne | 42055 | France |
| D007410 | Intestinal Diseases |