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

NCT03724929 | Terminated

• 2 other identifiers: 17082132018-001051-12
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Ulcerative Colitis

Keywords

Ulcerative Colitis; Vedolizumab; anti-vedolizumab

Outcome Measures

Primary Outcomes (1)

• Vedolizumab concentration at week 6

  Determine the optimal threshold of VDZ serum concentration measured at W6 capable to predict the clinical response at week 10 with VDZ.

  Week 6

Secondary Outcomes (9)

• Vedolizumab concentration at week 14

  Week 14

• vedolizumab concentration and anti-vedolizumab antibodies concentrations at week 2

  Week 2

• vedolizumab concentration and anti-vedolizumab antibodies concentrations at week 14

  Week 14

• Vedolizumab concentration at week 6 and mucosal healing

  Week 6

• Vedolizumab concentration at week 14 and mucosal healing

  Week 14

Study Arms (1)

Ulcerative Colitis patients

EXPERIMENTAL

To determine if the best cut-off points of vedolizumab (VDZ) trough levels measured at W6 capable to identify UC patients who will achieve a clinical response at week 10 with VDZ and also the best cut-off points of VDZ trough levels measured at W14 capable to identify UC patients who will achieve a clinical remission to maintenance therapy with VDZ : 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. Rectosigmoidoscopy will be performed in each center at time points W0, W10 and W52, to evaluate treatment efficacy. In cases of loss of response, rectosigmoidoscopy will be performed before and four weeks after optimization.

Procedure: Blood sample; Device: Rectosigmoidoscopy

Interventions

Blood sample PROCEDURE

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.

Ulcerative Colitis patients

Rectosigmoidoscopy DEVICE

Rectosigmoidoscopy will be performed in each center at time points W0, W10 and W52.

Ulcerative Colitis patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged over 18 years
• Men or non-pregnant women
• Patients with a diagnosis of ulcerative colitis who requires to start VDZ
• Moderate to severe active ulcerative colitis defined as a total mayo score ranging from 6 to 12 and endoscopic Mayo score above 1
• UC patients with previous failure with TNF antagonist agents and unacceptable side-effects from steroids, and/or immunosuppressive agents (i.e., azathioprine, 6-mercaptopurine, or methotrexate).
• Informed written consent given.

You may not qualify if:

• Existing pregnancy, lactation, or intended pregnancy within the next 15 months
• Minors or History of disease, including mental/emotional disorder that might interfere with their participation in the study
• Inability to comply with the protocol requirements
• Inability to fill in the diary cards during the last 3 days before each visit
• Severe Acute UC needed hospitalisation
• Known previous or concurrent malignancy (other than that considered surgically cured, with no evidence for recurrence for 5 years)
• Short bowel syndrome
• Previous treatments with vedolizumab, natalizumab, efalizumab or rituximab.
• Previous treatment with adalimumab within 30 days prior enrollment or infliximab and certolizumab pegol within 60 days before enrollment (This period may be shortened in the opinion of the investigator.)
• Prior extensive colonic resection, obstructive (symptomatic) intestinal stricture, abdominal abscess, active or latent tuberculosis,
• Clostridium difficile superinfection;
• Indeterminate colitis
• Concomitant leukocyte apheresis.
• Any contraindication to vedolizumab therapy
• Patients who denied the protocol, not ability to accept or sign consent of the protocol

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead
• Takeda: collaborator
• Theradiag: collaborator

Study Sites (5)

CHU Amiens

Amiens, 80000, France

Location

CHU Kremlin Bicêtre

Le Kremlin-Bicêtre, 94270, France

Location

Chu L'Archet

Nice, 06200, France

Location

Ch Lyon Sud

Pierre-Bénite, 69230, France

Location

CHU Saint-Etienne

Saint-Etienne, 42055, France

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Xavier ROBLIN

  CHU SAINT-ETIENNE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2018
• First Posted: October 30, 2018
• Study Start: March 4, 2019
• Primary Completion: April 15, 2022
• Study Completion: June 28, 2022
• Last Updated: May 23, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)