SAFARI: Predictive Factors of Clinical Response to Ustekinumab in Active Crohn's Disease

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Completed

CT.gov ID

NCT03351647

Collaborator

(none)

Enrollment

Location

19.3

Actual Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Ustekinumab is a fully human Immune Globulin Gk (IgGk) monoclonal antibody against the common p40 subunit of interleukin-12 and interleukin-23, which are implicated in the pathogenesis of inflammatory bowel disease. Its efficiency to induce and maintain clinical response in patients with anti TNF resistant Crohn's disease has been proved in several clinical trials, and the profile of safety of this treatment was good, but the investigators have few data about biological characteristics of patients treated by Ustekinumab, particularly about ustekinumab through levels and rate of patients developing anti ustekinumab antibodies during the induction and maintenance stages, and no predictive factors of clinical response have been identified yet.

The aim of this study will be to assess the evolution of biological markers of inflammation and ustekinumab trough levels and antibodies, in responders and non responders patients treated by ustekinumab, in order to identify predictive factors of clinical response.

The investigators will perform a prospective observational study, including the patients followed in the University hospital center of Lyon and treated by ustekinumab for a moderate to severe Crohn's disease (with a HBI score≥4 ). All the patients included will have been previously treated by at least one anti TNF and/or Vedolizumab, with specified criteria for a primary non response, a secondary loss of response or unacceptable side effects.

Then, clinical and biological data will be collected for each patient at the inclusion, and then at weeks 4, 8, 16, 24: HBI score, sides effects, extra intestinal manifestations, steroids withdraw, CRP, calprotectin, ustekinumab trough levels and ustekinumab antibodies.

The investigators will compare responding and non responding patients at week 16 (end of the induction period) according to these data.

The hypothesis the investigators state is that an early and significant decrease of the inflammation markers in blood and stools associated with a high ustekinumab through level in blood is associated with a clinical response at week 16 in the patients treated by ustekinumab

Condition or Disease	Intervention/Treatment	Phase
Crohn Disease	Biological: Evaluation of biological predictive factors of clinical response to ustekinumab

Study Design

Study Type:

Observational

Actual Enrollment :

18 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Identification of Biological Predictive Factors of Clinical Response to Ustekinumab in Patients With Anti-Tumor Necrosis Factor (TNF) Antagonists Refractory Crohn's Disease: Interest of Dosage of C Reactive Protein (CRP), Calprotectin, Ustekinumab Through Levels and Antibodies

Actual Study Start Date :

Feb 14, 2018

Actual Primary Completion Date :

Aug 29, 2018

Actual Study Completion Date :

Sep 23, 2019

Arms and Interventions

Arm	Intervention/Treatment
Group Ustekinumab Patients presenting an active crohn's disease (HBI score ≥ 4) with an indication of treatment by ustekinumab because of failure or unacceptable side effects of previous treatments, and who have already been treated by at least one anti TNF The patients must be 18 years old or older.	Biological: Evaluation of biological predictive factors of clinical response to ustekinumab The clinical response is defined as a decrease in the Crohn's Disease Activity Index (CDAI) score ≥ 100 points or a decrease in the HBI score ≥ 3 points.

Arm

Intervention/Treatment

Group Ustekinumab

Patients presenting an active crohn's disease (HBI score ≥ 4) with an indication of treatment by ustekinumab because of failure or unacceptable side effects of previous treatments, and who have already been treated by at least one anti TNF The patients must be 18 years old or older.

Biological: Evaluation of biological predictive factors of clinical response to ustekinumab

The clinical response is defined as a decrease in the Crohn's Disease Activity Index (CDAI) score ≥ 100 points or a decrease in the HBI score ≥ 3 points.

Outcome Measures

Primary Outcome Measures

Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 8. [Week 8]
Dosage of ustekinumab through level and ustekinumab antibodies: one 4ml blood sample

Secondary Outcome Measures

Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 4. [Week 4]
Dosage of ustekinumab through level and ustekinumab antibodies: one 4ml blood sample
Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 16. [Week 16]
Dosage of ustekinumab through level and ustekinumab antibodies: one 4ml blood sample
Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 24. [Week 24]
Dosage of ustekinumab through level and ustekinumab antibodies: one 4ml blood sample
Dosage in blood at week 4 [Week 4]
-Inflammation markers are evaluated : Dosage of CRP and leucocytes in blood: two 4ml blood sample
Dosage in blood at week 8 [Week 8]
-Inflammation markers are evaluated : Dosage of CRP and leucocytes in blood: two 4ml blood sample
Dosage in blood at week 16 [Week 16]
-Inflammation markers are evaluated : Dosage of CRP and leucocytes in blood: two 4ml blood sample
Dosage in blood at week 24 [Week 24]
-Inflammation markers are evaluated : Dosage of CRP and leucocytes in blood: two 4ml blood sample
Dosage of calprotectin in stools at week 4 [Week 4]
-Inflammation markers are evaluated : Dosage of calprotectin in stools: one about 50 mg stools sample
Dosage of calprotectin in stools at week 8 [Week 8]
-Inflammation markers are evaluated : Dosage of calprotectin in stools: one about 50 mg stools sample
Dosage of calprotectin in stools at week 16 [Week 16]
-Inflammation markers are evaluated : Dosage of calprotectin in stools: one about 50 mg stools sample
Dosage of calprotectin in stools at week 24 [Week 24]
-Inflammation markers are evaluated : Dosage of calprotectin in stools: one about 50 mg stools sample
Physical evaluation at week 4 [Week 4]
Clinical evaluation is realized by a medical visit with physical examination
Physical evaluation at week 8 [Week 8]
Clinical evaluation is realized by a medical visit with physical examination
Physical evaluation at week 16 [Week 16]
Clinical evaluation is realized by a medical visit with physical examination
Physical evaluation at week 24 [Week 24]
Clinical evaluation is realized by a medical visit with physical examination
Clinical evaluation at week 4 [Week 4]
Clinical evaluation is realized by a medical visit with evaluation of: the efficiency of the treatment: evaluation of well being, abdominal pain, stools numbers per day, presence or not of peri anal lesion, arthralgia, fever the tolerance/potential side effects of the treatment: infections, headache, skin rash, nausea, allergic reaction, or any clinical manifestation that could be imputed to the treatment
Clinical evaluation at week 8 [Week 8]
Clinical evaluation is realized by a medical visit with evaluation of: the efficiency of the treatment: evaluation of well being, abdominal pain, stools numbers per day, presence or not of peri anal lesion, arthralgia, fever the tolerance/potential side effects of the treatment: infections, headache, skin rash, nausea, allergic reaction, or any clinical manifestation that could be imputed to the treatment
Clinical evaluation at week 16 [Week 16]
Clinical evaluation is realized by a medical visit with evaluation of: the efficiency of the treatment: evaluation of well being, abdominal pain, stools numbers per day, presence or not of peri anal lesion, arthralgia, fever the tolerance/potential side effects of the treatment: infections, headache, skin rash, nausea, allergic reaction, or any clinical manifestation that could be imputed to the treatment
Clinical evaluation at week 24 [Week 24]
Clinical evaluation is realized by a medical visit with evaluation of: the efficiency of the treatment: evaluation of well being, abdominal pain, stools numbers per day, presence or not of peri anal lesion, arthralgia, fever the tolerance/potential side effects of the treatment: infections, headache, skin rash, nausea, allergic reaction, or any clinical manifestation that could be imputed to the treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age > 18 years old
Man or non pregnant woman
Diagnostic attested of Crohn's disease
Active Crohn's disease, with HBI score ≥ 4
Previous treatment by at least one anti TNF and / or vedolizumab,, with primary non response, secondary loss of response or unacceptable side effects
Formal indication of treatment by ustekinumab
Patient informed and not opposed to his participation at the study