VEDO - PREDIRESPUC project - Vedolizumab and anti-vedolizumab antibody in the prediction of therapeutic response in Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 24 September 2018
• Main ID: EUCTR2018-001051-12-FR
• Date of registration: 19/04/2018
• Prospective Registration: Yes
• Primary sponsor: CHU Saint-Etienne
• Public title: VEDO - PREDIRESPUC project - Vedolizumab and anti-vedolizumab antibody in the prediction of therapeutic response in Ulcerative Colitis
• Scientific title: VEDO - PREDIRESPUC project - Value of pharmacokinetic assays (Vedolizumab and anti-vedolizumab antibody) in the prediction of induction and maintenance therapeutic response in Ulcerative Colitis
• Date of first enrolment: 07/09/2018
• Target sample size: 125
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-001051-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

France

Contacts

• Name: Projet manager
• Affiliation: CHU Saint-Etienne

• Name: Projet manager
• Affiliation: CHU Saint-Etienne

Key inclusion & exclusion criteria

Inclusion criteria:
- 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). In France, VDZ has to be prescribed only in patients in failure or intolerant to anti-TNF.
- Stable doses of oral prednisone (=30 mg per day) or budesonide (=9 mg per day), are allowed at stable dose for at least 4 weeks-before inclusion. Concomitant immunosuppressive agents, mesalamine, are allowed at stable dose for at least three months before inclusion. Steroid tapering has to be set up at Week 6 after starting VDZ, according to the ECCO recommendations.
- Informed written consent given

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
- 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
- Serious secondary illnesses of an acute or chronic nature, which in the opinion of the investigator renders the patient unsuitable for inclusion into the study
- Inability to comply with the protocol requirements
- Inability to fill in the diary cards during the last 7 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
- 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
- Subject involved in another clinical trial



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Ulcerative Colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856
MedDRA version: 20.1 Level: LLT Classification code 10066678 Term: Acute ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Trade Name: ENTYVIO
Product Name: ENTYVIO
Product Code: 1
Pharmaceutical Form: Powder for concentrate and solution for solution for infusion

Primary Outcome(s)

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

Primary end point(s): VDZ concentrations were measured using the Lisa-Tracker Premium Vedolizumab enzyme-linked immunosorbent assay (ELISA) kit (Theradiag; Marne la Vallée France). This assay has been developed to reduce low affinity binding of immune complexes or interfering molecules such as the rheumatoid factor. The use of specific buffers for both binding and washing steps allows a very efficient capture of free molecules. VDZ was considered undetectable for a concentration< 0.1 µg/mL. The antibodies against Vedolizumab detection level reported by the manufacturer was > 10 ng/mL.
Clinical response is defined by a decrease in the Mayo score for at least three points and a decrease for at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore for at least one point or an absolute rectal bleeding subscore of 0 or 1.

Secondary Objective: Determine the optimal threshold of VDZ serum concentration measured at W14 capable to predict the clinical remission at week 52
Investigating whether the pharmacokinetic parameters of VDZ measured at W2 are predictive of a clinical response and clinical remission at W10
Investigating whether the pharmacokinetic parameters of VDZ measured at W14 are predictive of a clinical response and remission at W52
Analyzing the value of VDZ trough levels measured at W6 to predict mucosal healing at W10 under induction therapy
Analyzing the value of VDZ trough levels measured at W14 to predict mucosal healing at W52 under maintenance therapy
Investigating the intra and inter-individual heterogeneity of VDZ levels
Assessing the relationships between the variation of serum VDZ trough levels pre- and post-optimization (delta) and the clinical response in primary non-responder patients requiring additional infusions of VDZ.

Timepoint(s) of evaluation of this end point: week 10

Secondary Outcome(s)

Secondary end point(s): Clinical remission : Mayo clinical score of two or lower and no subscore higher than 1, and mucosal healing defined by an endoscopic subscore of 0 or 1
Mucosal healing: endoscopic subscore of 0 or 1
CRP normalization: < 5 mg/L
Dose intensification in patients with primary failure: absence of clinical response at W10: 300 mg VDZ at W10 and W14 and then every 8 weeks if subsequent response
Dose intensification in patients with secondary loss of response: infusion VDZ 300 mg every 4 weeks.

Timepoint(s) of evaluation of this end point: W52

Secondary ID(s)

1708213

Source(s) of Monetary Support

TAKEDA FRANCE