<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/NCT04481230</url>
  </required_header>
  <id_info>
    <org_study_id>2020-000495-37</org_study_id>
    <nct_id>NCT04481230</nct_id>
  </id_info>
  <brief_title>Assessment of 99mTc-NTP 15-5 Uptake on Cartilage, a New Proteoglycan Tracer</brief_title>
  <acronym>CARSPECT</acronym>
  <official_title>Assessment of 99mTc-NTP 15-5 Uptake on Cartilage, a New Proteoglycan Tracer: Phase I Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Jean Perrin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Jean Perrin</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a phase I clinical trial aimed to determine the recommended dose of 99mTc-NTP&#xD;
      15-5 to obtain the best tracer joints contrast on images without any toxicity.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 12, 2020</start_date>
  <completion_date type="Actual">September 19, 2022</completion_date>
  <primary_completion_date type="Actual">July 28, 2022</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>dose escalation model</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>determination of the recommended dose of 99mTc-NTP 15-5 to obtain the best tracer joints contrast on images without any toxicity</measure>
    <time_frame>Imaging at Day 0 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours post-injection)</time_frame>
    <description>defined as the dose from which 100% of patients will present a score 3 (semi-quantitative visual scale on whole body imaging) in at least 80% of healthy joints visualized on scintigraphies performed 2 h or less post-injection and without dose-limiting toxicity (DLT).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>dose-limiting toxicity (DLT)</measure>
    <time_frame>1 week after injection of the 99mTc-NTP 15-5 (Day 0)</time_frame>
    <description>defined as any grade 3-4 toxicity according to the NCI-CTCAE (version 4.03)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>3D quantification analysis</measure>
    <time_frame>imaging at Day 0, 30 minutes, 2 hours, 4 hours, 6-8 hours after injection of the 99mTc-NTP 15-5</time_frame>
    <description>TEMP Volumetric regions of interest (VOI) will be centered on cartilaginous zones, and on the corresponding bony diaphyses or vertebral body or the adjacent muscles. The articular uptake of 99mTc NTP-15-5 will thus be normalized to bone or muscle uptake.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of 99mTc-NTP 15-5 (frequence of adverse events)</measure>
    <time_frame>1 week after injection of the 99mTc-NTP 15-5 (Day 0)</time_frame>
    <description>according to the NCI-CTCAE (version 4.03)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biodistribution of 99mTc-NTP 15-5</measure>
    <time_frame>imaging at Day 0, 30 minutes, 2 hours, 4 hours, 6-8 hours after injection of the 99mTc-NTP 15-5</time_frame>
    <description>evaluated by measuring the percentage of injected activity of 99mTc-NTP 15-5 fixed on the target organs and on the pathological joints or healthy joints.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of 99mTc-NTP 15-5 by assessment of Area Under the Curve (AUC)</measure>
    <time_frame>at Day 0 during the first 8 hours after injection of the 99mTc-NTP 15-5</time_frame>
    <description>radiation counting on whole blood and on plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of 99mTc-NTP 15-5 by assessment of Maximum Concentration (Cmax)</measure>
    <time_frame>at Day 0 during the first 8 hours after injection of the 99mTc-NTP 15-5</time_frame>
    <description>radiation counting on whole blood and on plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of 99mTc-NTP 15-5 by assessment of the time take to reach Cmax (Tmax)</measure>
    <time_frame>at Day 0 during the first 8 hours after injection of the 99mTc-NTP 15-5</time_frame>
    <description>radiation counting on whole blood and on plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urinary elimination of 99mTc-NTP 15-5</measure>
    <time_frame>at Day 0 during the first 8 hours after injection of the 99mTc-NTP 15-5</time_frame>
    <description>by counting</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dosimetry</measure>
    <time_frame>imaging at Day 0, 30 minutes, 2 hours, 4 hours, 6-8 hours after injection of the 99mTc-NTP 15-5</time_frame>
    <description>measurement of the absorbed dose per organ will be evaluated by quantitative analysis.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Osteoarthritis, Knee</condition>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>99mTc-NTP 15-5 (level 1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>99mTc-NTP 15-5 at a diagnostic activity of 5 MBq/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>99mTc-NTP 15-5 (level 2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>99mTc-NTP 15-5 at a diagnostic activity of 10 MBq/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>99mTc-NTP 15-5 (level 3)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>99mTc-NTP 15-5 at a diagnostic activity of 15 MBq/kg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>99mTc-NTP 15-5 at a diagnostic activity of 5 MBq/kg</intervention_name>
    <description>1 intravenous injection of 99mTc-NTP 15-5 at a diagnostic activity of 5 MBq/kg (D0)</description>
    <arm_group_label>99mTc-NTP 15-5 (level 1)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>99mTc-NTP 15-5 at a diagnostic activity of 10 MBq/kg</intervention_name>
    <description>1 intravenous injection of 99mTc-NTP 15-5 at a diagnostic activity of 10 MBq/kg (D0)</description>
    <arm_group_label>99mTc-NTP 15-5 (level 2)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>99mTc-NTP 15-5 at a diagnostic activity of 15 MBq/kg</intervention_name>
    <description>1 intravenous injection of 99mTc-NTP 15-5 at a diagnostic activity of 15 MBq/kg (D0)</description>
    <arm_group_label>99mTc-NTP 15-5 (level 3)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Inclusion criteria specific to group 1:&#xD;
&#xD;
        - Patient with painful unilateral osteoarthritis of the knee as femorotibial pattern&#xD;
        defined by a radiographic score of 0/1 from Kellgren / Lawrence and an average WOMAC score&gt;&#xD;
        or equal to 4 and by minor disorders at MRI (MOCART 2.0 score&gt; 70).&#xD;
&#xD;
        Inclusion criteria specific to group 2:&#xD;
&#xD;
          -  Patient with non-metastatic breast cancer, hormone receptor positive, HER2 negative,&#xD;
             with indication for adjuvant therapy with aromatase inhibitor; treatment not yet&#xD;
             started.&#xD;
&#xD;
          -  Age &lt;60 years&#xD;
&#xD;
        Common inclusion criteria:&#xD;
&#xD;
          -  Patient with at least 31 healthy joints (based on clinical assessment)&#xD;
&#xD;
          -  signed written informed consent.&#xD;
&#xD;
          -  Affiliation to a health insurance scheme.&#xD;
&#xD;
          -  For women of childbearing age : negative serum pregnancy test at inclusion (less than&#xD;
             7 days prior injection of 99mTc-NTP 15-5).&#xD;
&#xD;
          -  Willing and able to comply with study visits, treatment, exams and the protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients &lt;18 years of age.&#xD;
&#xD;
          -  Pregnant or lactating patient.&#xD;
&#xD;
          -  BMI&gt; 30&#xD;
&#xD;
          -  History of known allergy to excipients contained in the solution of 99mTc-NTP 15-5&#xD;
&#xD;
          -  Chronic inflammatory rheumatism (rheumatoid arthritis, spondyloarthropathy, psoriatic&#xD;
             arthritis, etc.) diffuse arthritis (at least 3 joints affected), autoimmune&#xD;
             connectivitis, fibromyalgia.&#xD;
&#xD;
          -  Known chronic joint pathology: osteoarthritis affecting at least 3 joints, autoimmune&#xD;
             disease, inflammatory rheumatism (except unilateral knee arthritis).&#xD;
&#xD;
          -  Persons deprived of their liberty, under guardianship / curatorship, or safeguard of&#xD;
             justice.&#xD;
&#xD;
          -  Treatment with NSAIDs or cessation of less than 48 h.&#xD;
&#xD;
          -  Inability to comply with medical requirement / follow-up of the trial for geographic,&#xD;
             family, social or psychological reasons. These conditions should be discussed with the&#xD;
             patient before registration in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Florent CACHIN, Pr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Jean Perrin</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre Jean Perrin</name>
      <address>
        <city>Clermont-Ferrand</city>
        <zip>63011</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Clermont-Ferrand</name>
      <address>
        <city>Clermont-Ferrand</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 2, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>March 6, 2023</last_update_submitted>
  <last_update_submitted_qc>March 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cartilage</keyword>
  <keyword>proteoglycan tracer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis, Knee</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/NCT04481230
org study id: 2020-000495-37
nct id: NCT04481230
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is a phase I clinical trial aimed to determine the recommended dose of 99mTc-NTP
      15-5 to obtain the best tracer joints contrast on images without any toxicity.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: dose escalation model
primary purpose: Diagnostic
masking: None (Open Label)
measure: determination of the recommended dose of 99mTc-NTP 15-5 to obtain the best tracer joints contrast on images without any toxicity
time frame: Imaging at Day 0 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours post-injection)
description: defined as the dose from which 100% of patients will present a score 3 (semi-quantitative visual scale on whole body imaging) in at least 80% of healthy joints visualized on scintigraphies performed 2 h or less post-injection and without dose-limiting toxicity (DLT).
measure: dose-limiting toxicity (DLT)
time frame: 1 week after injection of the 99mTc-NTP 15-5 (Day 0)
description: defined as any grade 3-4 toxicity according to the NCI-CTCAE (version 4.03)
measure: 3D quantification analysis
time frame: imaging at Day 0, 30 minutes, 2 hours, 4 hours, 6-8 hours after injection of the 99mTc-NTP 15-5
description: TEMP Volumetric regions of interest (VOI) will be centered on cartilaginous zones, and on the corresponding bony diaphyses or vertebral body or the adjacent muscles. The articular uptake of 99mTc NTP-15-5 will thus be normalized to bone or muscle uptake.
measure: Safety of 99mTc-NTP 15-5 (frequence of adverse events)
time frame: 1 week after injection of the 99mTc-NTP 15-5 (Day 0)
description: according to the NCI-CTCAE (version 4.03)
measure: Biodistribution of 99mTc-NTP 15-5
time frame: imaging at Day 0, 30 minutes, 2 hours, 4 hours, 6-8 hours after injection of the 99mTc-NTP 15-5
description: evaluated by measuring the percentage of injected activity of 99mTc-NTP 15-5 fixed on the target organs and on the pathological joints or healthy joints.
measure: Pharmacokinetics of 99mTc-NTP 15-5 by assessment of Area Under the Curve (AUC)
time frame: at Day 0 during the first 8 hours after injection of the 99mTc-NTP 15-5
description: radiation counting on whole blood and on plasma
measure: Pharmacokinetics of 99mTc-NTP 15-5 by assessment of Maximum Concentration (Cmax)
time frame: at Day 0 during the first 8 hours after injection of the 99mTc-NTP 15-5
description: radiation counting on whole blood and on plasma
measure: Pharmacokinetics of 99mTc-NTP 15-5 by assessment of the time take to reach Cmax (Tmax)
time frame: at Day 0 during the first 8 hours after injection of the 99mTc-NTP 15-5
description: radiation counting on whole blood and on plasma
measure: Urinary elimination of 99mTc-NTP 15-5
time frame: at Day 0 during the first 8 hours after injection of the 99mTc-NTP 15-5
description: by counting
measure: Dosimetry
time frame: imaging at Day 0, 30 minutes, 2 hours, 4 hours, 6-8 hours after injection of the 99mTc-NTP 15-5
description: measurement of the absorbed dose per organ will be evaluated by quantitative analysis.
arm group label: 99mTc-NTP 15-5 (level 1)
arm group type: Experimental
description: 99mTc-NTP 15-5 at a diagnostic activity of 5 MBq/kg
arm group label: 99mTc-NTP 15-5 (level 2)
arm group type: Experimental
description: 99mTc-NTP 15-5 at a diagnostic activity of 10 MBq/kg
arm group label: 99mTc-NTP 15-5 (level 3)
arm group type: Experimental
description: 99mTc-NTP 15-5 at a diagnostic activity of 15 MBq/kg
intervention type: Drug
intervention name: 99mTc-NTP 15-5 at a diagnostic activity of 5 MBq/kg
description: 1 intravenous injection of 99mTc-NTP 15-5 at a diagnostic activity of 5 MBq/kg (D0)
arm group label: 99mTc-NTP 15-5 (level 1)
intervention type: Drug
intervention name: 99mTc-NTP 15-5 at a diagnostic activity of 10 MBq/kg
description: 1 intravenous injection of 99mTc-NTP 15-5 at a diagnostic activity of 10 MBq/kg (D0)
arm group label: 99mTc-NTP 15-5 (level 2)
intervention type: Drug
intervention name: 99mTc-NTP 15-5 at a diagnostic activity of 15 MBq/kg
description: 1 intravenous injection of 99mTc-NTP 15-5 at a diagnostic activity of 15 MBq/kg (D0)
arm group label: 99mTc-NTP 15-5 (level 3)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Florent CACHIN, Pr
role: Principal Investigator
affiliation: Centre Jean Perrin
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Osteoarthritis, Knee