Crohn DiseaseSAFARINCT03351647
Predictive Factors of Clinical Response to Ustekinumab in Active Crohn's Disease
An observational study of Crohn Disease, run by Hospices Civils de Lyon at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 18 to 18 years
- Conditions the study is for
- Crohn Disease
- What is being tested?
- Evaluation of biological predictive factors of clinical response to ustekinumab
- How many people
- 18 participants
- Where
- 1 siteFrance
- Study dates
- 14 Feb 2018to 23 Sep 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 18 years
- All sexes
- No healthy volunteers
- Adult
Study population: This study is conducted in adults with moderate to severe active Crohn's disease who are resistant to TNF and Vedolizumab.
Who may be able to join
- 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
Who cannot join
- Pregnancy
- Evolutive cancer
- Evolutive and uncontrolled infection
- Psychiatric pathology that could interfere with the follow-up
- Refusal of the patient
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read more
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
- Conditions
- Crohn Disease
- Being tested
- Evaluation of biological predictive factors of clinical response to ustekinumab
- Keywords
- Crohn Disease, Ustekinumab, Vedolizumab, anti-TNF, CRP, calprotectin, cohort
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Evaluation of biological predictive factors of clinical response to ustekinumabBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Evaluation of biological predictive factors of clinical response to ustekinumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Week 8
Secondary outcomes (19)
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
Measured: Week 4
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
Measured: Week 16
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
Measured: Week 24
Dosage in blood at week 4
-Inflammation markers are evaluated : Dosage of CRP and leucocytes in blood: two 4ml blood sample
Measured: Week 4
Dosage in blood at week 8
-Inflammation markers are evaluated : Dosage of CRP and leucocytes in blood: two 4ml blood sample
Measured: Week 8
Dosage in blood at week 16
-Inflammation markers are evaluated : Dosage of CRP and leucocytes in blood: two 4ml blood sample
Measured: Week 16
Dosage in blood at week 24
-Inflammation markers are evaluated : Dosage of CRP and leucocytes in blood: two 4ml blood sample
Measured: Week 24
Dosage of calprotectin in stools at week 4
-Inflammation markers are evaluated : Dosage of calprotectin in stools: one about 50 mg stools sample
Measured: Week 4
Dosage of calprotectin in stools at week 8
-Inflammation markers are evaluated : Dosage of calprotectin in stools: one about 50 mg stools sample
Measured: Week 8
Dosage of calprotectin in stools at week 16
-Inflammation markers are evaluated : Dosage of calprotectin in stools: one about 50 mg stools sample
Measured: Week 16
Dosage of calprotectin in stools at week 24
-Inflammation markers are evaluated : Dosage of calprotectin in stools: one about 50 mg stools sample
Measured: Week 24
Physical evaluation at week 4
Clinical evaluation is realized by a medical visit with physical examination
Measured: Week 4
Physical evaluation at week 8
Clinical evaluation is realized by a medical visit with physical examination
Measured: Week 8
Physical evaluation at week 16
Clinical evaluation is realized by a medical visit with physical examination
Measured: Week 16
Physical evaluation at week 24
Clinical evaluation is realized by a medical visit with physical examination
Measured: Week 24
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
Measured: Week 4
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
Measured: Week 8
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
Measured: Week 16
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
Measured: Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2017
- Study start14 Feb 2018
- Primary completion29 Aug 2018
- Study completion23 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03351647
- Sponsor's protocol ID
- 69HCL17_0218
- Acronym
- SAFARI
- Status last verified
- Aug 2022
- First submitted
- 30 Oct 2017
- Last updated
- 24 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03351647
- Acronym / sponsor ID
- SAFARI / 69HCL17_0218
- Conditions
- Crohn Disease
- Keywords
- Crohn Disease, Ustekinumab, Vedolizumab, anti-TNF, CRP, calprotectin, cohort
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 14 Feb 2018 (actual)
- Primary completion
- 29 Aug 2018 (actual)
- Study completion
- 23 Sep 2019 (actual)
- First posted
- 24 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Group Ustekinumab | – | Biological: Evaluation of biological predictive factors of clinical response to ustekinumabPatients 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. |
Who may qualify
- Ages
- 18 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- This study is conducted in adults with moderate to severe active Crohn's disease who are resistant to TNF and Vedolizumab.
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (5 listed)
- Pregnancy
- Evolutive cancer
- Evolutive and uncontrolled infection
- Psychiatric pathology that could interfere with the follow-up
- Refusal of the patient
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Evaluation of biological predictive factors of clinical response to ustekinumabThe 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. | Biological | Group Ustekinumab |
Primary outcome
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
19 secondary outcomes
Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 4.
Time frame: Week 4
Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 16.
Time frame: Week 16
Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 24.
Time frame: Week 24
Dosage in blood at week 4
Time frame: Week 4
Dosage in blood at week 8
Time frame: Week 8
Dosage in blood at week 16
Time frame: Week 16
Dosage in blood at week 24
Time frame: Week 24
Dosage of calprotectin in stools at week 4
Time frame: Week 4
Dosage of calprotectin in stools at week 8
Time frame: Week 8
Dosage of calprotectin in stools at week 16
Time frame: Week 16
Dosage of calprotectin in stools at week 24
Time frame: Week 24
Physical evaluation at week 4
Time frame: Week 4
Physical evaluation at week 8
Time frame: Week 8
Physical evaluation at week 16
Time frame: Week 16
Physical evaluation at week 24
Time frame: Week 24
Clinical evaluation at week 4
Time frame: Week 4
Clinical evaluation at week 8
Time frame: Week 8
Clinical evaluation at week 16
Time frame: Week 16
Clinical evaluation at week 24
Time frame: Week 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Crohn Disease, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 8. (time frame: Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2022.