<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03033095</url>
  </required_header>
  <id_info>
    <org_study_id>38RC16.018</org_study_id>
    <nct_id>NCT03033095</nct_id>
  </id_info>
  <brief_title>Prediction of the Answer to the Treatment by Biotherapies for Naive Spondyloarthritis by Combinatorial Analysis of Serum Biomarkers</brief_title>
  <acronym>PRESA</acronym>
  <official_title>Prediction of the Answer to the Treatment by Biotherapies for Naive Spondyloarthritis Disease During 6 Months by Combinatorial Analysis of Serum Biomarkers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Grenoble</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Grenoble</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this trial is the caracterisation of a predicting algorithm of the answering&#xD;
      response for patients with etanercept treatment in spondyloarthritis disease.&#xD;
&#xD;
      This algorithm will help to target patients patients who have a risk / benefit important for&#xD;
      etanercept treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Spondyloarthritis (or spondyloarthropathy) is an inflammatory rheumatic disease that causes&#xD;
      arthritis. It differs from other types of arthritis because it involves the sites where&#xD;
      ligaments and tendons are attached to bones called &quot;entheses.&quot;&#xD;
&#xD;
      All patients should get physical therapy and make exercises for joints. Exercises that&#xD;
      promote spinal extension and mobility are the most recommended.&#xD;
&#xD;
      Non-steroidal anti-inflammatory drugs (NSAIDs) are the first line treatment for&#xD;
      spondylarthritis. NSAIDs are effective when they are used continuously or at the request, in&#xD;
      a short or long-term use. However, physicians have to be aware of potential cardiovascular,&#xD;
      renal or gastro-intestinal secondary effects when they prescribe NSAIDs. After NSAIDs&#xD;
      failure, TNF inhibitors can be used, like infliximab or etanercept. Before starting an&#xD;
      anti-TNF treatment, a screening is mandatory. Indeed, patients treated with an anti-TNF must&#xD;
      be followed regularly. Until now, there is no algorithm which can predict the response to&#xD;
      TNF-inhibitors, and more especially for etanercept treatment.&#xD;
&#xD;
      In this clinical trial, the investigators want to caracterise an algorithm which can predict&#xD;
      the response to etanercept for a cohort of patients who suffer from spondyloarthritis.&#xD;
&#xD;
      The development of a predictive algorithm for etanercept treatment will be set up from&#xD;
      biological data and finalized with the availibility of clinical data (M6) of the patients .&#xD;
&#xD;
      A modelling by logistic regression will be used, incorporing the set of available variables.&#xD;
&#xD;
      In this clinical trial, the investigators want to caracterise an algorithm which can predict&#xD;
      the response to TNF-inhibitors for a cohort of patients with Spondyloarthritis and for an&#xD;
      indicated treatment of etanercept.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2016</start_date>
  <completion_date type="Actual">March 28, 2018</completion_date>
  <primary_completion_date type="Actual">July 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Measurement of disease activity with AS- DAS score (Ankylosing Spondylitis - Disease Activity Score )</measure>
    <time_frame>6 months after inclusion</time_frame>
    <description>An important clinical ASAS response, corresponds to a variation of the ASDAS CRP ≥ 1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measurement of BASDAI response</measure>
    <time_frame>6 months after inclusion</time_frame>
    <description>Sensitivity and specificity of the algorithm for BASDAI response : BASDAI response 50, that means an improvement of BASDAI response of 50% or more</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>biomarkers analysis for personalized medicine</measure>
    <time_frame>at the inclusion and 6 months after</time_frame>
    <description>8 biomarkers will be analysed :&#xD;
calcium-binding protein complex S100A8/A9,&#xD;
prealbumin,&#xD;
haptoglobin (Hapto),&#xD;
protéine C-réactive (CRP),&#xD;
α1 anti-trypsin&#xD;
apolipoprotéinA1 (ApoA1),&#xD;
platelet factor 4 (PF4),&#xD;
S100A12 protein,</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Spondylitis, Ankylosing</condition>
  <arm_group>
    <arm_group_label>etanercept</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The etanercept is not the experimental study drug. Etanercept is a treatment justifying the inclusion of patients and is used in accordance with its marketing authorization.&#xD;
Modality of administration :&#xD;
Etanercept : 50 mg / week subcutaneously, every 7 days The clinical response will be evaluated after 6 months of etanercept treatment, at the M6 visit.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etanercept ® 50 mg</intervention_name>
    <description>The etanercept is not the experimental study drug. Etanercept is a treatment justifying the inclusion of patients and is used in accordance with its marketing authorization.</description>
    <arm_group_label>etanercept</arm_group_label>
    <other_name>ENBREL</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients with spondylarthritis validating ASAS or New York modified critera, and for&#xD;
             who etanercept is indicated.&#xD;
&#xD;
          -  Naïve from biological Drug Modifying Anti Rheumatic Drugs&#xD;
&#xD;
          -  patients between 18 and 70 years old&#xD;
&#xD;
          -  patients who can be monitored at 6 months ;&#xD;
&#xD;
          -  patients who can observe the entire treatment ;&#xD;
&#xD;
          -  patiens with age to procreate under effective contraception ((abstinence, oral&#xD;
             contraceptives , intrauterine devices , implants, spermicide or surgical sterilization&#xD;
             ) during the study and for 6 months, 3 weeks after the last injection.&#xD;
&#xD;
          -  patients able to understand and accept the terms of the study&#xD;
&#xD;
          -  patients having signed the informed consent.&#xD;
&#xD;
          -  patients insured under social security&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients of age protected ;&#xD;
&#xD;
          -  patients with difficulties for understanding french language ;&#xD;
&#xD;
          -  patients with high function disorders incompatible with an education program (dementia&#xD;
             Alzheimer's type , etc ...) ;&#xD;
&#xD;
          -  patients with psycho- social instability incompatible with regular monitoring&#xD;
             (homeless , addictive behavior ,etc.) ;&#xD;
&#xD;
          -  patients in a socio- professional situation incompatible with optimal attendance to&#xD;
             the program - - Pregnant or nursing patients&#xD;
&#xD;
          -  patients who received previously a biotherapy treatment . There is no other exclusion&#xD;
             criteria taking into account previous treatments and the duration of them.&#xD;
&#xD;
          -  contraindication to the use of anti- TNF treatment&#xD;
&#xD;
          -  Surgery scheduled during the study.&#xD;
&#xD;
          -  Persons mentioned in Articles L.1121-5 to L.1121-8 of the Public Health Code&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Athan BAILLET</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Grenoble</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Grenoble</name>
      <address>
        <city>Grenoble</city>
        <zip>38043</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Aaltonen KJ, Virkki LM, Malmivaara A, Konttinen YT, Nordstrom DC, Blom M. Systematic review and meta-analysis of the efficacy and safety of existing TNF blocking agents in treatment of rheumatoid arthritis. PLoS One. 2012;7(1):e30275. doi: 10.1371/journal.pone.0030275. Epub 2012 Jan 17.</citation>
    <PMID>22272322</PMID>
  </reference>
  <reference>
    <citation>Braun J, Sieper J. Biological therapies in the spondyloarthritides--the current state. Rheumatology (Oxford). 2004 Sep;43(9):1072-84. doi: 10.1093/rheumatology/keh205. Epub 2004 Jun 8.</citation>
    <PMID>15187239</PMID>
  </reference>
  <reference>
    <citation>Kristensen LE, Saxne T, Nilsson JA, Geborek P. Impact of concomitant DMARD therapy on adherence to treatment with etanercept and infliximab in rheumatoid arthritis. Results from a six-year observational study in southern Sweden. Arthritis Res Ther. 2006;8(6):R174. doi: 10.1186/ar2084.</citation>
    <PMID>17121678</PMID>
  </reference>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>May 11, 2016</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>June 13, 2022</last_update_submitted>
  <last_update_submitted_qc>June 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>TNF inhibitor</keyword>
  <keyword>Etanercept</keyword>
  <keyword>Spondyloarthritis</keyword>
  <keyword>Biomarkers analysis</keyword>
  <keyword>Personnalized medicine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spondylitis</mesh_term>
    <mesh_term>Spondylarthritis</mesh_term>
    <mesh_term>Spondylitis, Ankylosing</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Etanercept</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03033095
org study id: 38RC16.018
nct id: NCT03033095
lead sponsor: 
has dmc: No
The aim of this trial is the caracterisation of a predicting algorithm of the answering
      response for patients with etanercept treatment in spondyloarthritis disease.

      This algorithm will help to target patients patients who have a risk / benefit important for
      etanercept treatment.
Spondyloarthritis (or spondyloarthropathy) is an inflammatory rheumatic disease that causes
      arthritis. It differs from other types of arthritis because it involves the sites where
      ligaments and tendons are attached to bones called "entheses."

      All patients should get physical therapy and make exercises for joints. Exercises that
      promote spinal extension and mobility are the most recommended.

      Non-steroidal anti-inflammatory drugs (NSAIDs) are the first line treatment for
      spondylarthritis. NSAIDs are effective when they are used continuously or at the request, in
      a short or long-term use. However, physicians have to be aware of potential cardiovascular,
      renal or gastro-intestinal secondary effects when they prescribe NSAIDs. After NSAIDs
      failure, TNF inhibitors can be used, like infliximab or etanercept. Before starting an
      anti-TNF treatment, a screening is mandatory. Indeed, patients treated with an anti-TNF must
      be followed regularly. Until now, there is no algorithm which can predict the response to
      TNF-inhibitors, and more especially for etanercept treatment.

      In this clinical trial, the investigators want to caracterise an algorithm which can predict
      the response to etanercept for a cohort of patients who suffer from spondyloarthritis.

      The development of a predictive algorithm for etanercept treatment will be set up from
      biological data and finalized with the availibility of clinical data (M6) of the patients .

      A modelling by logistic regression will be used, incorporing the set of available variables.

      In this clinical trial, the investigators want to caracterise an algorithm which can predict
      the response to TNF-inhibitors for a cohort of patients with Spondyloarthritis and for an
      indicated treatment of etanercept.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Screening
masking: None (Open Label)
measure: Measurement of disease activity with AS- DAS score (Ankylosing Spondylitis - Disease Activity Score )
time frame: 6 months after inclusion
description: An important clinical ASAS response, corresponds to a variation of the ASDAS CRP ≥ 1.1
measure: Measurement of BASDAI response
time frame: 6 months after inclusion
description: Sensitivity and specificity of the algorithm for BASDAI response : BASDAI response 50, that means an improvement of BASDAI response of 50% or more
measure: biomarkers analysis for personalized medicine
time frame: at the inclusion and 6 months after
description: 8 biomarkers will be analysed :
calcium-binding protein complex S100A8/A9,
prealbumin,
haptoglobin (Hapto),
protéine C-réactive (CRP),
α1 anti-trypsin
apolipoprotéinA1 (ApoA1),
platelet factor 4 (PF4),
S100A12 protein,
arm group label: etanercept
arm group type: Experimental
description: The etanercept is not the experimental study drug. Etanercept is a treatment justifying the inclusion of patients and is used in accordance with its marketing authorization.
Modality of administration :
Etanercept : 50 mg / week subcutaneously, every 7 days The clinical response will be evaluated after 6 months of etanercept treatment, at the M6 visit.
intervention type: Drug
intervention name: Etanercept ® 50 mg
description: The etanercept is not the experimental study drug. Etanercept is a treatment justifying the inclusion of patients and is used in accordance with its marketing authorization.
arm group label: etanercept
other name: ENBREL
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Athan BAILLET
role: Principal Investigator
affiliation: University Hospital, Grenoble
facility: 
country: France
citation: Aaltonen KJ, Virkki LM, Malmivaara A, Konttinen YT, Nordstrom DC, Blom M. Systematic review and meta-analysis of the efficacy and safety of existing TNF blocking agents in treatment of rheumatoid arthritis. PLoS One. 2012;7(1):e30275. doi: 10.1371/journal.pone.0030275. Epub 2012 Jan 17.
PMID: 22272322
citation: Braun J, Sieper J. Biological therapies in the spondyloarthritides--the current state. Rheumatology (Oxford). 2004 Sep;43(9):1072-84. doi: 10.1093/rheumatology/keh205. Epub 2004 Jun 8.
PMID: 15187239
citation: Kristensen LE, Saxne T, Nilsson JA, Geborek P. Impact of concomitant DMARD therapy on adherence to treatment with etanercept and infliximab in rheumatoid arthritis. Results from a six-year observational study in southern Sweden. Arthritis Res Ther. 2006;8(6):R174. doi: 10.1186/ar2084.
PMID: 17121678
responsible party type: Sponsor
mesh term: Spondylitis
mesh term: Spondylarthritis
mesh term: Spondylitis, Ankylosing
mesh term: Etanercept
sharing ipd: No