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Completed

NCT Number: NCT03351647

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

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

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Key information

Conditions

Crohn Disease Digestive System Diseases Gastroenteritis Gastrointestinal Diseases Inflammatory Bowel Diseases Intestinal Diseases

Age range

18 year–18 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Centre hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Evaluation of biological predictive factors of clinical response to ustekinumab

Biological

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.

Primary outcomes

  1. Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 8.

    Time frame: Week 8

    Dosage of ustekinumab through level and ustekinumab antibodies: one 4ml blood sample

Secondary outcomes

  1. Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 4.

    Time frame: Week 4

    Dosage of ustekinumab through level and ustekinumab antibodies: one 4ml blood sample

  2. Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 16.

    Time frame: Week 16

    Dosage of ustekinumab through level and ustekinumab antibodies: one 4ml blood sample

  3. Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 24.

    Time frame: Week 24

    Dosage of ustekinumab through level and ustekinumab antibodies: one 4ml blood sample

  4. Dosage in blood at week 4

    Time frame: Week 4

    -Inflammation markers are evaluated : Dosage of CRP and leucocytes in blood: two 4ml blood sample

  5. Dosage in blood at week 8

    Time frame: Week 8

    -Inflammation markers are evaluated : Dosage of CRP and leucocytes in blood: two 4ml blood sample

  6. Dosage in blood at week 16

    Time frame: Week 16

    -Inflammation markers are evaluated : Dosage of CRP and leucocytes in blood: two 4ml blood sample

  7. Dosage in blood at week 24

    Time frame: Week 24

    -Inflammation markers are evaluated : Dosage of CRP and leucocytes in blood: two 4ml blood sample

  8. Dosage of calprotectin in stools at week 4

    Time frame: Week 4

    -Inflammation markers are evaluated : Dosage of calprotectin in stools: one about 50 mg stools sample

  9. Dosage of calprotectin in stools at week 8

    Time frame: Week 8

    -Inflammation markers are evaluated : Dosage of calprotectin in stools: one about 50 mg stools sample

  10. Dosage of calprotectin in stools at week 16

    Time frame: Week 16

    -Inflammation markers are evaluated : Dosage of calprotectin in stools: one about 50 mg stools sample

  11. Dosage of calprotectin in stools at week 24

    Time frame: Week 24

    -Inflammation markers are evaluated : Dosage of calprotectin in stools: one about 50 mg stools sample

  12. Physical evaluation at week 4

    Time frame: Week 4

    Clinical evaluation is realized by a medical visit with physical examination

  13. Physical evaluation at week 8

    Time frame: Week 8

    Clinical evaluation is realized by a medical visit with physical examination

  14. Physical evaluation at week 16

    Time frame: Week 16

    Clinical evaluation is realized by a medical visit with physical examination

  15. Physical evaluation at week 24

    Time frame: Week 24

    Clinical evaluation is realized by a medical visit with physical examination

  16. Clinical evaluation at week 4

    Time frame: 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

  17. Clinical evaluation at week 8

    Time frame: 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

  18. Clinical evaluation at week 16

    Time frame: 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

  19. Clinical evaluation at week 24

    Time frame: 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

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Official study 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

Acronym: SAFARI

Important dates

Study start
2018
Primary completion
2018
Study completion
2019
First posted
Nov 24, 2017
Registry last updated
Aug 24, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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