Ignite Creation Date:
2025-12-24 @ 2:54 PM
Ignite Modification Date:
2025-12-24 @ 2:54 PM
Study NCT ID:
NCT02954159
Status:
TERMINATED
Last Update Posted:
2020-09-03
First Post:
2016-10-14
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Vedolizumab Monotherapy Vs Combination Therapy With Tacrolimus in UC
Sponsor:
Medical College of Wisconsin
Organization:
Study Overview
Official Title:
Induction of Response and Remission of Vedolizumab Monotherapy Vs Combination Therapy With Tacrolimus in Patients With Moderately to Severely Active Ulcerative Colitis
Status:
TERMINATED
Status Verified Date:
2020-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
insufficient enrollment
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
COVET
Brief Summary:
The aim of this study is to assess if a combination therapy of tacrolimus and vedolizumab is superior to vedolizumab monotherapy for induction of remission in moderate to severe UC, and its effect on long and short-term outcomes including colectomy rate. Secondary aim of this study is to assess the safety of tacrolimus as an induction agent in patients with UC.
Detailed Description:
Phase III studies have shown that patients with UC who received vedolizumab had a higher rate of clinical response, clinical remission and mucosal healing when compared to placebo3. Nevertheless, while clinical response rate was almost 50%, the rate of clinical remission at 6 weeks was only 16.9. In comparison, in the ACT trials almost 40% of patients achieved remission at week 84. The delayed onset of action of vedolizumab monotherapy in patients with UC may lead to a higher colectomy rate and limit the use of vedolizumab in patients with active disease who require rapid induction of remission. Corticosteroids are used as a bridging agent to rapidly induce remission. However, steroid refractory or dependent disease and steroid intolerance are common. Furthermore, steroids have devastating side effects.
Tacrolimus inhibits the complexion of calcineurin with its respective cytoplasmic receptors cyclophilin and FK-binding protein 12 (FKBP-12), both of which regulate a calmodulin dependent-phosphatase. Tacrolimus has been found to be efficacious in the treatment of patients with moderate to severe UC. Unfortunately, because of the safety profile with long term use, the drug is mostly used as an induction agent.
While switching to vedolizumab from another drug that has not been efficacious or has lost effectiveness (or starting vedolizumab as a first agent) can be beneficious in the long term, patients need an induction agent in order to achieve remission in a short period of time. Tacrolimus is a widely used drug to prevent implant rejection after a transplant. Randomized controlled trials have shown that is highly effective with good response rates even after 2 weeks of therapy. In order to avoid side effects, tacrolimus is usually used for a limited amount of time (12-14 weeks), which is sufficient time to induce remission of disease. Unfortunately, as other inflammatory bowel diseases, UC recurs and patients also require a maintenance therapy. While tacrolimus has been used with good results as a long term agent, the ideal scenario is to avoid its long term use as there is still a potential for side effects and a need for a very strict close monitoring. This is why a long term maintenance agent is needed to keep the patient in remission. Until recently, no ideal agent was available for this purpose, as while anti-tumor necrosis factor agents (infliximab and adalimumab) have been approved for ulcerative colitis, its combination with another agent that induces systemic immunosuppression (in this case, tacrolimus) could potentially increase the risk of infections and/or malignancies. Because vedolizumab is gut selective, does not affect the entire immune system and post-marketing studies have confirmed its safety profile. This makes it a perfect combination agent to tacrolimus, theoretically decreasing the potential side effect while increasing its efficacy.
The hypothesis is that the addition of tacrolimus as an induction agent to a standard regimen of vedolizumab increases the efficacy of the drug, decreasing the rate of need for colectomy and other complications while quickly improving the patients' quality of life without significantly increasing the risk of adverse events.
Tacrolimus inhibits the complexion of calcineurin with its respective cytoplasmic receptors cyclophilin and FK-binding protein 12 (FKBP-12), both of which regulate a calmodulin dependent-phosphatase. Tacrolimus has been found to be efficacious in the treatment of patients with moderate to severe UC. Unfortunately, because of the safety profile with long term use, the drug is mostly used as an induction agent.
While switching to vedolizumab from another drug that has not been efficacious or has lost effectiveness (or starting vedolizumab as a first agent) can be beneficious in the long term, patients need an induction agent in order to achieve remission in a short period of time. Tacrolimus is a widely used drug to prevent implant rejection after a transplant. Randomized controlled trials have shown that is highly effective with good response rates even after 2 weeks of therapy. In order to avoid side effects, tacrolimus is usually used for a limited amount of time (12-14 weeks), which is sufficient time to induce remission of disease. Unfortunately, as other inflammatory bowel diseases, UC recurs and patients also require a maintenance therapy. While tacrolimus has been used with good results as a long term agent, the ideal scenario is to avoid its long term use as there is still a potential for side effects and a need for a very strict close monitoring. This is why a long term maintenance agent is needed to keep the patient in remission. Until recently, no ideal agent was available for this purpose, as while anti-tumor necrosis factor agents (infliximab and adalimumab) have been approved for ulcerative colitis, its combination with another agent that induces systemic immunosuppression (in this case, tacrolimus) could potentially increase the risk of infections and/or malignancies. Because vedolizumab is gut selective, does not affect the entire immune system and post-marketing studies have confirmed its safety profile. This makes it a perfect combination agent to tacrolimus, theoretically decreasing the potential side effect while increasing its efficacy.
The hypothesis is that the addition of tacrolimus as an induction agent to a standard regimen of vedolizumab increases the efficacy of the drug, decreasing the rate of need for colectomy and other complications while quickly improving the patients' quality of life without significantly increasing the risk of adverse events.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: