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

Crohn Disease Clinical Trial

— SAFARI  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03351647
• Other study ID #: 69HCL17_0218
• Status: Completed
• Start date: February 14, 2018
• Est. completion date: September 23, 2019

Study information

• Verified date: August 2022
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: September 23, 2019
• Est. primary completion date: August 29, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 18 Years

Eligibility

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

Exclusion Criteria:

• Pregnancy

• Evolutive cancer

• Evolutive and uncontrolled infection

• Psychiatric pathology that could interfere with the follow-up

• Refusal of the patient

Related Conditions & MeSH terms

• Crohn Disease

Intervention

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.

Locations

Country	Name	City	State
France	Centre hospitalier Lyon Sud	Pierre-Bénite

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 8.	Dosage of ustekinumab through level and ustekinumab antibodies: one 4ml blood sample	Week 8
Secondary	Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 4.	Dosage of ustekinumab through level and ustekinumab antibodies: one 4ml blood sample	Week 4
Secondary	Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 16.	Dosage of ustekinumab through level and ustekinumab antibodies: one 4ml blood sample	Week 16
Secondary	Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 24.	Dosage of ustekinumab through level and ustekinumab antibodies: one 4ml blood sample	Week 24
Secondary	Dosage in blood at week 4	-Inflammation markers are evaluated : Dosage of CRP and leucocytes in blood: two 4ml blood sample	Week 4
Secondary	Dosage in blood at week 8	-Inflammation markers are evaluated : Dosage of CRP and leucocytes in blood: two 4ml blood sample	Week 8
Secondary	Dosage in blood at week 16	-Inflammation markers are evaluated : Dosage of CRP and leucocytes in blood: two 4ml blood sample	Week 16
Secondary	Dosage in blood at week 24	-Inflammation markers are evaluated : Dosage of CRP and leucocytes in blood: two 4ml blood sample	Week 24
Secondary	Dosage of calprotectin in stools at week 4	-Inflammation markers are evaluated : Dosage of calprotectin in stools: one about 50 mg stools sample	Week 4
Secondary	Dosage of calprotectin in stools at week 8	-Inflammation markers are evaluated : Dosage of calprotectin in stools: one about 50 mg stools sample	Week 8
Secondary	Dosage of calprotectin in stools at week 16	-Inflammation markers are evaluated : Dosage of calprotectin in stools: one about 50 mg stools sample	Week 16
Secondary	Dosage of calprotectin in stools at week 24	-Inflammation markers are evaluated : Dosage of calprotectin in stools: one about 50 mg stools sample	Week 24
Secondary	Physical evaluation at week 4	Clinical evaluation is realized by a medical visit with physical examination	Week 4
Secondary	Physical evaluation at week 8	Clinical evaluation is realized by a medical visit with physical examination	Week 8
Secondary	Physical evaluation at week 16	Clinical evaluation is realized by a medical visit with physical examination	Week 16
Secondary	Physical evaluation at week 24	Clinical evaluation is realized by a medical visit with physical examination	Week 24
Secondary	Clinical evaluation at 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	Week 4
Secondary	Clinical evaluation at 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	Week 8
Secondary	Clinical evaluation at 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	Week 16
Secondary	Clinical evaluation at 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	Week 24