prediction of response to therapy in inflammatory bowel disease

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2018-002925-47-ES
• Date of registration: 16/11/2018
• Prospective Registration: Yes
• Primary sponsor: Fundación de Investigación Biomédica del Hospital Universitario de La Princesa
• Public title: prediction of response to therapy in inflammatory bowel disease
• Scientific title: Identification of predictive biomarkers for response to biologic therapies in inflammatory bowel disease by proteomic and mass cytometry approaches
• Date of first enrolment: 28/12/2018
• Target sample size: 180
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-002925-47
• 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: 6
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Spain

Contacts

• Name: Ana Garre
• Affiliation: fundación de Investigación Biomédica Hospital Universitario de La Princesa

• Name: Ana Garre
• Affiliation: fundación de Investigación Biomédica Hospital Universitario de La Princesa

Key inclusion & exclusion criteria

Inclusion criteria:
Group 1: Patients with IBD

- Over 18 years.
- Diagnosis of IBD according to the criteria of the European Crohns and Colitis Organization (ECCO).
- Have indication of treatment with a biologic drug.
- Be the first received biologic drug with a given mechanism of action (anti-TNFa, anti-a4ß7 or anti-p40).
- Have endoscopic activity of IBD within 1 month of starting the biologic treatment (see definitions section: SES-CD = 3 in CD and endoscopic sub-index of May = 2 in UC).
- In the case of CD, receive the biologic treatment by luminal activity (not perianal).
- Previous treatments (including corticosteroids and immunosuppressants) are allowed provided that they have been stable for the last 3 months prior to beginning treatment with biologics and that they are maintained at a stable dose for the duration of the study.

Group 2: patients without IBD

- Patients not diagnosed with IBD, or other inflammatory, allergic, malignant or autoimmune diseases, where a ilecolonoscopy is performed due to the normal clinical practice.
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 30

Exclusion criteria:
Group 1: Patients with IBD

- Under 18 years old.
- Having an immune-mediated disease other than IBD at the baseline visit.
- Having a neoplasm or an active infection at the time of the baseline visit.
- Pregnancy or lactation.
- Alcohol or drug abuse.
- Ostomy.
- Abdominal surgery in the last 6 months.
- Colectomy in patients with UC.
- Active infection with hepatitis B, C or HIV virus.
- Indication of biologic treatment for a cause other than IBD.
- Indication of biologic treatment to prevent postoperative recurrence in CD.
- Have previously received a biologic drug with the same mechanism of action of the drug indicated by your doctor (anti-TNFa, anti-a4ß7 or anti-p40).
- Refusal to give consent for participation in the study.

Group 2: patients without IBD

- Under 18 years old.
- Advanced chronic disease or any other pathology that prevents the follow-up of the protocol of this study.
- Pregnancy or lactation.
- Active infection with hepatitis B, C or HIV virus.
- Alcohol or drug abuse.
- Finding of macroscopic alterations during the ilecolonoscopy, or finding of relevant inflammatory alterations in the biopsies obtained during the ilecolonoscopy.
- Treatment with immunomodulators, immunosuppressants, corticosteroids or other drugs that alter the immune system.
- Refusal to give consent for participation in the study.


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

Health Condition(s) or Problem(s) studied

Inflammatory bowel disease
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 10017947 - Gastrointestinal disorders
MedDRA version: 20.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

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

Intervention(s)

Trade Name: Adalimumab
Pharmaceutical Form: Injection
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Trade Name: Infliximab
Pharmaceutical Form: 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: Golimumab
Pharmaceutical Form: Injection
INN or Proposed INN: GOLIMUMAB
CAS Number: 476181-74-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Ustekinumab
Pharmaceutical Form: Injection
INN or Proposed INN: USTEKINUMAB
CAS Number: 815610-63-0
Other descriptive name: USTEKINUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 90-

Trade Name: Vedolizumab
Pharmaceutical Form: Infusion
INN or Proposed INN: VEDOLIZUMAB
CAS Number: 943609-66-3
Other descriptive name: VEDOLIZUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Primary Outcome(s)

Main Objective: identify novel biomarkers of clinical response to the different available therapies in IBD, including Crohn´s disease (CD) and ulcerative colitis (UC).

Primary end point(s): Endoscopic response (main endpoint):

- In patients with CD, the endoscopic response will be defined as a >50% decrease in the SES-CD [78] 14 weeks after starting the biologic treatment. As a secondary variable, endoscopic response will be also defined as a decrease =3 points in the SES-CD (considered as a clinically significant endoscopic improvement) [80]. There is consensus that the evaluation of the response to treatment (and therefore the consideration of a patient as a primary non-responder) should not be performed before week 12-14 (in patients treated with anti-TNFa drugs) [13, 19, 81].
- In patients with UC, the endoscopic response will be defined as a decrease of =1 point in the Mayo endoscopic sub-score [82] 14 weeks after starting the biologic treatment.

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

Secondary Objective: 1. To determine the presence and severity of endoscopic inflammation by non-invasive approaches (in the absence of a ilecolonoscopy), before starting treatment and on the follow-up period, with the aim of monitoring treatment response.
2. To identify the immune cell subsets and signalling pathways specifically modulated by each of the biologic treatments in responding patients, both in CD and UC.
3. To identify similarities and differences on the mechanism of action of a given drug in both UC and CD.

Secondary Outcome(s)

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

Secondary end point(s): Endoscopic activity:

- In patients with CD, it will be evaluated using the Simplified Endoscopic Activity Score for Crohn's Disease [64, 76-78] (SES-CD); Endoscopic activity will be considered when the SES-CD is =3. In operated patients, or in those where the endoscopic exploration is incomplete, the SES-CD will be calculated according to the explorable segments, considering the previously described activity criterion.
- In patients with UC, it will be evaluated by the Mayo endoscopic sub-score [61, 79]; endoscopic activity will be considered as =2.
- The assessment of endoscopic activity will be carried out centrally by sending anonymized endoscopic images.

Endoscopic remission:

- In patients with CD, endoscopic remission will be defined as a SES-CD =2, 14 weeks after starting the biologic treatment.
- In patients with UC, endoscopic remission will be defined as an endoscopic subscript =1, 14 weeks after starting the biologic treatment.

Clinical activity:

- In patients with CD, it will be evaluated using the Crohn's Disease Activity Index (CDAI) [83]. Clinical remission will be considered as a CDAI <150 points 14 weeks after starting the biologic treatment; and clinical response, reduction of CDAI by 100 (R-100) or 70 points (R-70) [83].
- In patients with UC it will be evaluated by the partial Mayo index [83]. Clinical remission will be considered as a partial Mayo index =2, with all the scores (of the partial index) of 1 as a maximum and with a sub-score of rectal bleeding of 0, 14 weeks after starting the biologic treatment [83]; and clinical response, the decrease of 3 or more points (of the partial index) with respect to the baseline situation [84].

Secondary ID(s)

GIS-2018-BioIBD

Source(s) of Monetary Support

Instituto de Salud Carlos III

Ethics review

Status: Approved
Approval date:
Contact: