<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/NCT01713842</url>
  </required_header>
  <id_info>
    <org_study_id>RB 11-075 TENOR</org_study_id>
    <nct_id>NCT01713842</nct_id>
  </id_info>
  <brief_title>Tocilizumab Effect iN pOlymyalgia Rheumatica</brief_title>
  <acronym>TENOR</acronym>
  <official_title>Phase II Open 24 Weeks Study to Evaluate Effect and Safety of Tocilizumab as the First Line Therapy in Subjects With Polymyalgia Rheumatica (PMR)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Brest</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chugai Pharmaceutical</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Brest</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase 1:&#xD;
&#xD;
      Patients are treated with infusions of Tocilizumab (TCZ) for 3 months. Clinical evaluation is&#xD;
      performed using PMR-AS.&#xD;
&#xD;
      The PMR-AS is computed by summing the 5 variables after multiplying by 0.1 for weighting&#xD;
      purposes: PMR-AS (activity scale = AS) = C reactive protein (CRP) (mg/dl) + patient scale&#xD;
      (VASp) (0-10 scale) + physician scale (VASph) (0-10 scale) + morning stiffness(MST)&#xD;
      [min]×0.1) + elevation of upper limbs (EUL) (0-3 scale).&#xD;
&#xD;
      At the end of the phase 1,the patients stop TCZ and entered in phase 2 at week 12.&#xD;
&#xD;
      Phase 2:&#xD;
&#xD;
      All the patients are included in the phase 2 and treated with glucocorticoid (GC)for 3&#xD;
      months. Two arms are possible according to the PMR-AS. Either the classical GC treatment&#xD;
      (0.3mg/kg), either a low dose group of GC(0.15mg/kg) .&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">October 2014</completion_date>
  <primary_completion_date type="Actual">October 2014</primary_completion_date>
  <phase>Phase 2</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy at W12</measure>
    <time_frame>12 Weeks</time_frame>
    <description>PMR-AS at week 12</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety and efficacy during the study</measure>
    <time_frame>Week 2,4,8,12,16,20 and 24</time_frame>
    <description>To maintain low disease activity (PMR-AS) in the low corticosteroid dose group from W12 to W24&#xD;
On the inflammatory changes (synovitis, myositis, tenosynovitis aund bursitis) between baseline, W2 and 12 visualize by ultrasonography, MRI and Tep-Scan.&#xD;
On sparing corticosteroid, with the comparison of the cumulative corticosteroid dosage beetwen the two groups of patients in the phase 2, W12 to 24.&#xD;
On the circulating serum cytokines and immunoregulators (IL-6, IL-1, BLyS/BAFF, IL-6 receptor, gp130) and B cells receptors and on the phenotype of circulating T- and B-cells between baseline and W4 and 12 On inflammatory parameters (CRP and ESR) between baseline and W 2,4,8,12,16,20 and 24&#xD;
On the quality of life of patients between baseline and W 4,12,16, 20 and 24&#xD;
To evaluate the side-effects in relation to the use of Tocilizumab treatment. [ Time Frame: After first, second and third treatment and during follow up ]</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Polymyalgia Rheumatica</condition>
  <arm_group>
    <arm_group_label>TCZ</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tocilizumab at week 0, week 4 and week 8 8mg/kg at each perfusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TCZ</intervention_name>
    <description>Tocilizumab at week 0, 4 and 8.</description>
    <arm_group_label>TCZ</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age between 50 years and 75 years included&#xD;
&#xD;
          -  PMR-AS &gt; 10&#xD;
&#xD;
          -  PMR according to the Chuang criteria&#xD;
&#xD;
          -  Evolving since less than 12 months&#xD;
&#xD;
          -  Without Horton disease&#xD;
&#xD;
          -  Able to understand and accept the study&#xD;
&#xD;
          -  Agree to sign the inform consent form&#xD;
&#xD;
          -  Without GC, or at least during 1 month and stop since 7 days before the inclusion.&#xD;
&#xD;
          -  Stable dose of Nonsteroidal anti-inflammatory since 4 weeks before the inclusion.&#xD;
&#xD;
          -  Birth controlled during all the study and 6 months after&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Disagree to participated&#xD;
&#xD;
          -  Unable to understand the study&#xD;
&#xD;
          -  Participation to an other study in the 3 months before the inclusion&#xD;
&#xD;
          -  Treated by GC at 0.3mg/kg/d in the past 7 days&#xD;
&#xD;
          -  Less than 50 years old or more than 75 years old&#xD;
&#xD;
          -  Uncontrolled dyslipidemia, high blood pressure or cardiovascular disease&#xD;
&#xD;
          -  Histories of important allergy&#xD;
&#xD;
          -  Historically positive test or test positive at screening for HIV-1 antibody, hepatitis&#xD;
             B surface antigen, or hepatitis C antibody.&#xD;
&#xD;
          -  Abnormal screening blood test : leukocyte count less than 3.5 × 109 cells/L,&#xD;
             neutrophil count less than 2 × 109 cells/L, hemoglobin level less than 85 g/L,&#xD;
             platelet count less than 100 × 109 cells/L, or hepatic aminotransferase or alkaline&#xD;
             phosphatase levels greater than 3 times the upper limit of normal&#xD;
&#xD;
          -  Other inflammatory rheumatic disease or connective disease&#xD;
&#xD;
          -  Clinical evidence of significant unstable or uncontrolled acute or chronic diseases&#xD;
             not due to PMR (eg. Cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic,&#xD;
             renal, neurological, malignancy or infectious diseases)&#xD;
&#xD;
          -  Current drug or alcohol abuse&#xD;
&#xD;
          -  Patients treated with an immunosuppressive agents in the past 4 weeks&#xD;
&#xD;
          -  Live/attenuated vaccine in the past 4 weeks&#xD;
&#xD;
          -  Clinical symptoms of giant cell arteritis&#xD;
&#xD;
          -  History of infection or infestation in the past 3 months&#xD;
&#xD;
          -  Active tuberculosis&#xD;
&#xD;
          -  Planned surgical procedure&#xD;
&#xD;
          -  History of malignant neoplasm within the last 5 years, except for adequately treated&#xD;
             cancer of the skin (basal or squamous cell)&#xD;
&#xD;
          -  History or current tumoral hematological disease&#xD;
&#xD;
          -  Severe allergic or anaphylactic reactions about one of the TCZ component&#xD;
&#xD;
          -  Pregnant women during the study and six month after the end of the study&#xD;
&#xD;
          -  Breast feeding mother&#xD;
&#xD;
          -  Dysthyroidia&#xD;
&#xD;
          -  Unstable treatment by statin in the past 3 months&#xD;
&#xD;
          -  Parkinson disease&#xD;
&#xD;
          -  Fibromyalgia&#xD;
&#xD;
          -  Peripheric arthritis&#xD;
&#xD;
          -  Articular chondrocalcinosis or hydorxyapatites rhumatisms&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Valérie DEVAUCHELLE, Pr</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHRU de Brest</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brest University Hospital</name>
      <address>
        <city>Brest</city>
        <zip>29609</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nantes University Hospital</name>
      <address>
        <city>Nantes</city>
        <zip>44000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHR d'Orléans</name>
      <address>
        <city>Orléans</city>
        <zip>45000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>January 2015</verification_date>
  <study_first_submitted>September 17, 2012</study_first_submitted>
  <study_first_submitted_qc>October 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 25, 2012</study_first_posted>
  <last_update_submitted>February 10, 2015</last_update_submitted>
  <last_update_submitted_qc>February 10, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 11, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Tocilizumab</keyword>
  <keyword>Polymyalgia Rheumatica</keyword>
  <keyword>Glucocorticotherapy</keyword>
  <keyword>PMR-AS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polymyalgia Rheumatica</mesh_term>
    <mesh_term>Giant Cell Arteritis</mesh_term>
  </condition_browse>
  <!-- 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/NCT01713842
org study id: RB 11-075 TENOR
nct id: NCT01713842
lead sponsor: 
collaborator: 
has dmc: Yes
Phase 1:

      Patients are treated with infusions of Tocilizumab (TCZ) for 3 months. Clinical evaluation is
      performed using PMR-AS.

      The PMR-AS is computed by summing the 5 variables after multiplying by 0.1 for weighting
      purposes: PMR-AS (activity scale = AS) = C reactive protein (CRP) (mg/dl) + patient scale
      (VASp) (0-10 scale) + physician scale (VASph) (0-10 scale) + morning stiffness(MST)
      [min]×0.1) + elevation of upper limbs (EUL) (0-3 scale).

      At the end of the phase 1,the patients stop TCZ and entered in phase 2 at week 12.

      Phase 2:

      All the patients are included in the phase 2 and treated with glucocorticoid (GC)for 3
      months. Two arms are possible according to the PMR-AS. Either the classical GC treatment
      (0.3mg/kg), either a low dose group of GC(0.15mg/kg) .
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Efficacy at W12
time frame: 12 Weeks
description: PMR-AS at week 12
measure: Safety and efficacy during the study
time frame: Week 2,4,8,12,16,20 and 24
description: To maintain low disease activity (PMR-AS) in the low corticosteroid dose group from W12 to W24
On the inflammatory changes (synovitis, myositis, tenosynovitis aund bursitis) between baseline, W2 and 12 visualize by ultrasonography, MRI and Tep-Scan.
On sparing corticosteroid, with the comparison of the cumulative corticosteroid dosage beetwen the two groups of patients in the phase 2, W12 to 24.
On the circulating serum cytokines and immunoregulators (IL-6, IL-1, BLyS/BAFF, IL-6 receptor, gp130) and B cells receptors and on the phenotype of circulating T- and B-cells between baseline and W4 and 12 On inflammatory parameters (CRP and ESR) between baseline and W 2,4,8,12,16,20 and 24
On the quality of life of patients between baseline and W 4,12,16, 20 and 24
To evaluate the side-effects in relation to the use of Tocilizumab treatment. [ Time Frame: After first, second and third treatment and during follow up ]
arm group label: TCZ
arm group type: Experimental
description: Tocilizumab at week 0, week 4 and week 8 8mg/kg at each perfusion
intervention type: Drug
intervention name: TCZ
description: Tocilizumab at week 0, 4 and 8.
arm group label: TCZ
criteria: 
gender: All
minimum age: 50 Years
maximum age: 80 Years
healthy volunteers: No
last name: Valérie DEVAUCHELLE, Pr
role: Principal Investigator
affiliation: CHRU de Brest
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Polymyalgia Rheumatica
mesh term: Giant Cell Arteritis