EFFICACI : EFFicacy of intravenous Infliximab versus vedolizumab after failure of subCutaneous Anti-TNF in patients with UlCerative colitis : A double blinded Randomized Clinical Trial.

• Register: EUCTR
• Last refreshed on: 10 October 2018
• Main ID: EUCTR2018-002673-21-FR
• Date of registration: 06/07/2018
• Prospective Registration: Yes
• Primary sponsor: Centre Hospitalier Universitaire de Rennes
• Public title: EFFICACI : EFFicacy of intravenous Infliximab versus vedolizumab after failure of subCutaneous Anti-TNF in patients with UlCerative colitis : A double blinded Randomized Clinical Trial.
• Scientific title: EFFICACI : EFFicacy of intravenous Infliximab versus vedolizumab after failure of subCutaneous Anti-TNF in patients with UlCerative colitis : A double blinded Randomized Clinical Trial. - EFFICACI
• Date of first enrolment: 04/09/2018
• Target sample size: 150
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-002673-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• 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: Diection de la Recherche
• Affiliation: Centre Hospitalier Universitaire de Rennes

• Name: Diection de la Recherche
• Affiliation: Centre Hospitalier Universitaire de Rennes

Key inclusion & exclusion criteria

Inclusion criteria:
? Male or non-pregnant female, non-lactating female;
? 18 years of age or older and less than 75 years ;
? Documented diagnosis of UC for at least 6 months ;
? Left side colitis or pancolitis ;
? Moderate to severe disease according to a Mayo score equal or above 6 with a Mayo endoscopic sub-score of 2 or 3 ;
? Active disease despite ongoing treatment with adalimumab or golimumab for at least 12 weeks (inadequate response, failure, loss of response or intolerance) ;
? Ability of the subject to participate fully in all aspects of this clinical trial ;
? Written informed consent must be obtained and documented ;
? Naïve to JAK inhibitor ;
? Affiliation to the national health insurance.

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 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

Exclusion criteria:
? Contraindication to continue TNF antagonist (ongoing abscess(es), clinical suspicion of tuberculosis, past allergic reaction) ;
? Contraindication to vedolizumab treatment ;
? Steroid treatment > 20 mg/day for at least two weeks before baseline ;
? Proctitis ;
? Stoma ;
? Proctocolectomy or subtotal colectomy ;
? Planned surgery within the year of the trial ;
? Previous exposure to vedolizumab or infliximab ;
? History of cancer during the past 5 years ;
? Pregnancy or breastfeeding
? Adults legally protected (under judicial protection, guardianship, or supervision), persons deprived of their liberty.
? Ongoing participation to another interventional study



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

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]

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

Intervention(s)

Trade Name: Remicade
Product Name: infliximab
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 5-

Trade Name: Inflectra
Product Name: infliximab
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 5-

Trade Name: Flixabi
Product Name: infliximab
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 5-

Trade Name: Remsima
Product Name: infliximab
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 5-

Trade Name: Entyvio
Product Name: Vedolizumab
Pharmaceutical Form: Powder for solution for infusion
CAS Number: 943609-66-3
Other descriptive name: VEDOLIZUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: week 14

Secondary Objective: ? To assess the rate of clinical response and remission at Week 54 in each group of treatments and the time to clinical response and remission from baseline ;
? To assess the changes in faecal calprotectin levels from baseline to week 14 and 54 according to treatment ;
? To assess the rate of colectomy and hospitalization in each treatment group ;
? To assess the rate of mucosal healing at week 14 and 54 in each group of treatments ;
To assess the rate of loss of response
To assess the changes of quality of life indexes and the disability index
To determine the safety profile
To characterize the response according to drug monitoring of the first anti-TNF agent
To describe the pharmacokinetics of infliximab and vedolizumab and explore the sources of pharmacokinetic inter-individual variability
To identify predictive factors of response to the treatment, including pharmacokinetic features

Primary end point(s): The rate of patients with clinical and endoscopic steroid free-remission (Mayo score = 2 without subscore > 1) at week 14.

Main Objective: To determine whether a non-TNF-targeted biologic (vedolizumab) is superior to infliximab to treat patient with UC losing response or with a primary failure to a first subcutaneous anti-TNF drug at week 14.

Secondary Outcome(s)

Secondary end point(s): ? Mayo score at week 54 ;
? Faecal calprotectine level at week 14 and 54 ;
? Colectomy or hospitalization for disease flare during the study period ;
? Endoscopic subscore of the mayo Score at week 14 and 54 ;
? Partial Mayo score at week 2, 6, 14, 54 ;
? IBDQ index, IBD-Disk and IBD-DI at baseline week 14 and 54
? Rate and type of adverse events during the study period ;
? Last trough concentration of the first subcutaneous agent at the time of the loss of response and anti-drug antibodies concentration ;
? Trough concentration of infliximab or vedolizumab at each visit and anti-drug antibodies concentration.

Timepoint(s) of evaluation of this end point: week 2, 6, 14 and 54

Secondary ID(s)

35RC17_8841_EFFICACI

Source(s) of Monetary Support

PHRC National 2017