xml: <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/NCT05983848</url>
    </required_header>
    <id_info>
      <org_study_id>825832</org_study_id>
      <nct_id>NCT05983848</nct_id>
    </id_info>
    <brief_title>Scintigraphy for Prediction In Rheumatoid Intentional Therapy Tapering</brief_title>
    <acronym>SPIRITT</acronym>
    <official_title>An Observational Study Exploring the Value 99mMaracticaltide Imaging for Predicting Outcomes for Patients With Rheumatoid Arthritis Undergoing Tapering of Therapy</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Guy's and St Thomas' NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>The Leeds Teaching Hospitals NHS Trust</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Serac Healthcare</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Versus Arthritis</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Guy's and St Thomas' NHS Foundation Trust</source>
    <oversight_info>
      <has_dmc>No</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>
        The goal of this observational study is to investigate whether 99mTc-maraciclatide imaging&#xD;
        prior to biologic therapy tapering and after 3 months can predict those at risk of Rheumatoid&#xD;
        arthritis flare.&#xD;
  &#xD;
        Participants undergoing routine tapering of biologic drug therapy will have&#xD;
        99mTc-maraciclatide imaging in addition to normal ultrasound imaging and then followed up&#xD;
        over 12 months to assess whether an interval scan alone or in combination with the baseline&#xD;
        scan is predictive of flare.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Rheumatoid arthritis is a chronic inflammatory condition affecting the joints which over time&#xD;
        can cause progressive arthritis and disability. Since the introduction of widespread us of&#xD;
        targeted biologic therapies. More patients are now maintained in remission and low disease&#xD;
        activity with better long-term outcomes. Making treatment decisions can be challenging as&#xD;
        disease activity scores do not always reflect inflammatory disease activity and active&#xD;
        inflammation may be present but not manifested by clinically obvious swelling. Ultrasound,&#xD;
        and in particular power Doppler (PD), has been shown to be a more sensitive indicator of&#xD;
        active inflammatory disease and is widely used in clinical practice to inform decision&#xD;
        making.&#xD;
  &#xD;
        However, ultrasound is time consuming and thus expensive and it is impractical to image more&#xD;
        than a few joints routinely. We have shown that 99mTc-maraciclatide, a nuclear imaging agent&#xD;
        that uses equipment routinely available in hospitals, correlates with PD and hence has&#xD;
        potential as an accessible, more cost effective and, as is has the potential to image all the&#xD;
        joints in a single acquisition, more clinically informative alternative.&#xD;
  &#xD;
        Many patients on biologic therapy achieve low disease activity and may be suitable for&#xD;
        tapering of medication. This has the advantage of reducing exposure to immunosuppressive&#xD;
        medication and reducing costs. Whilst many patients can be tapered safely it is not always&#xD;
        clear who is at risk of flaring. It is known that the presence of PD signal can predict&#xD;
        higher risk, but this is not routinely used in practice for the reasons above. In this study&#xD;
        we will investigate whether 99mTc-maraciclatide imaging prior to tapering and after 3 months&#xD;
        can predict those at risk of flare. Success will indicate that it could be used in clinical&#xD;
        practice with potential to minimise exposure to unnecessary treatment whilst preserving&#xD;
        clinical outcomes, improving patient experience and reducing costs.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">October 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">October 1, 2025</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Cross-Sectional</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>99mTc-maraciclatide is predictive of risk of flare</measure>
      <time_frame>12 months</time_frame>
      <description>The purpose of this study is to determine whether baseline 99mTc-maraciclatide is predictive of risk of flare in RA patients tapering biologic therapy who are in in low disease activity or remission</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Interval and Baseline scan</measure>
      <time_frame>12 months</time_frame>
      <description>To determine whether an interval scan alone or in combination with the baseline scan is predictive of flare</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ultrasound correlation</measure>
      <time_frame>12 months</time_frame>
      <description>To determine whether ultrasound (grey scale and power Doppler) correlates with 99mTc-maraciclatide in this patient cohort at the whole patient and individual joint level</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serological correlation</measure>
      <time_frame>12 months</time_frame>
      <description>To determine correlation between 99mTc-maraciclatide imaging and clinical and serological markers of disease activity</description>
    </secondary_outcome>
    <enrollment type="Anticipated">86</enrollment>
    <condition>Rheumatoid Arthritis</condition>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>99mMaracticaltide imaging</intervention_name>
      <description>7.3.1 99mTc-maraciclatide imaging This will be undertaken at baseline and optionally at 8-12 weeks. Not more than 75 µg of 99mTc-maraciclatide will be administered intravenously with an activity as close as possible to 740 MBq. Static whole-body imaging will be undertaken after a maximum of 2 hours with further dedicated views of the hands and feet. Total image acquisition time will be approximately 30 minutes. Images will be scored by quantitative and semi-quantitative methods by a blinded observer.</description>
    </intervention>
    <biospec_retention>Samples With DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Additional study bloods (20ml) will be taken at baseline and 6-month visits for serological&#xD;
        markers of inflammation and neoangiogenesis. Serum samples will be given a trial ID and&#xD;
        stored in the Infectious Disease Biobank, King's College London. Samples will be processed,&#xD;
        stored and disposed in accordance with all applicable legal and regulatory requirements,&#xD;
        including the Human Tissue Act 2004 and any amendments thereafter.&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          RA patients selected for treatment tapering&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. A diagnosis of RA according to American College of Rheumatology/EULAR criteria.&#xD;
  &#xD;
            2. Clinical remission or LDA and deemed suitable for treatment tapering by their&#xD;
               supervising rheumatologist.&#xD;
  &#xD;
            3. Existing TNF inhibitor therapy (adalimumab, etanercept, certolizumab pegol, golimumab,&#xD;
               infliximab) administered at doses and dosing intervals that have been stable for ≥ 6&#xD;
               months.&#xD;
  &#xD;
            4. Aged between 18 and 80 years of age&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Recently received IM/IA steroids (12 weeks washout required).&#xD;
  &#xD;
            2. The subject was previously entered into this study or has participated in any other&#xD;
               investigational drug or medical device study within 30 days of enrolment.&#xD;
  &#xD;
            3. The subject has known allergies to maraciclatide or any constituent of its injectate.&#xD;
  &#xD;
            4. The subject size or weight is not compatible with imaging as determined by the&#xD;
               investigator.&#xD;
  &#xD;
            5. The subject has received any radiopharmaceutical within 7 days or 10 half-lives prior&#xD;
               to the imaging day (Day 0).&#xD;
  &#xD;
            6. The subject is pregnant or lactating.&#xD;
  &#xD;
            7. The subject has severe renal dysfunction, with estimated glomerular filtration rate&#xD;
               (eGFR) &lt;30 ml/min/1.73m2.&#xD;
  &#xD;
            8. The subject has hepatic insufficiency as demonstrated by ALT (alanine aminotransferase&#xD;
               [SGPT]) or AST (aspartate aminotransferase [SGOT]) &gt;3 times the upper limit of normal.&#xD;
  &#xD;
            9. The subject presents with any other clinically active, serious, life-threatening&#xD;
               disease with a life expectancy of less than 12 months or where participation in the&#xD;
               study might compromise the management of the subject or other reason that in the&#xD;
               judgment of the investigator(s) makes the subject unsuitable for participation in the&#xD;
               study.&#xD;
  &#xD;
           10. The subject is claustrophobic or has a movement disorder that prevents him/her from&#xD;
               lying still in a supine position for up to 20 minutes at a time.&#xD;
  &#xD;
           11. Patients who are currently involved in interventional trials will not be suitable&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
    </eligibility>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 2, 2023</study_first_submitted>
    <study_first_submitted_qc>August 2, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 2, 2023</last_update_submitted>
    <last_update_submitted_qc>August 2, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Arthritis</mesh_term>
      <mesh_term>Arthritis, Rheumatoid</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05983848
  org study id: 825832
  nct id: NCT05983848
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this observational study is to investigate whether 99mTc-maraciclatide imaging
        prior to biologic therapy tapering and after 3 months can predict those at risk of Rheumatoid
        arthritis flare.
  
        Participants undergoing routine tapering of biologic drug therapy will have
        99mTc-maraciclatide imaging in addition to normal ultrasound imaging and then followed up
        over 12 months to assess whether an interval scan alone or in combination with the baseline
        scan is predictive of flare.
  Rheumatoid arthritis is a chronic inflammatory condition affecting the joints which over time
        can cause progressive arthritis and disability. Since the introduction of widespread us of
        targeted biologic therapies. More patients are now maintained in remission and low disease
        activity with better long-term outcomes. Making treatment decisions can be challenging as
        disease activity scores do not always reflect inflammatory disease activity and active
        inflammation may be present but not manifested by clinically obvious swelling. Ultrasound,
        and in particular power Doppler (PD), has been shown to be a more sensitive indicator of
        active inflammatory disease and is widely used in clinical practice to inform decision
        making.
  
        However, ultrasound is time consuming and thus expensive and it is impractical to image more
        than a few joints routinely. We have shown that 99mTc-maraciclatide, a nuclear imaging agent
        that uses equipment routinely available in hospitals, correlates with PD and hence has
        potential as an accessible, more cost effective and, as is has the potential to image all the
        joints in a single acquisition, more clinically informative alternative.
  
        Many patients on biologic therapy achieve low disease activity and may be suitable for
        tapering of medication. This has the advantage of reducing exposure to immunosuppressive
        medication and reducing costs. Whilst many patients can be tapered safely it is not always
        clear who is at risk of flaring. It is known that the presence of PD signal can predict
        higher risk, but this is not routinely used in practice for the reasons above. In this study
        we will investigate whether 99mTc-maraciclatide imaging prior to tapering and after 3 months
        can predict those at risk of flare. Success will indicate that it could be used in clinical
        practice with potential to minimise exposure to unnecessary treatment whilst preserving
        clinical outcomes, improving patient experience and reducing costs.
  observational model: Cohort
  time perspective: Cross-Sectional
  measure: 99mTc-maraciclatide is predictive of risk of flare
  time frame: 12 months
  description: The purpose of this study is to determine whether baseline 99mTc-maraciclatide is predictive of risk of flare in RA patients tapering biologic therapy who are in in low disease activity or remission
  measure: Interval and Baseline scan
  time frame: 12 months
  description: To determine whether an interval scan alone or in combination with the baseline scan is predictive of flare
  measure: Ultrasound correlation
  time frame: 12 months
  description: To determine whether ultrasound (grey scale and power Doppler) correlates with 99mTc-maraciclatide in this patient cohort at the whole patient and individual joint level
  measure: Serological correlation
  time frame: 12 months
  description: To determine correlation between 99mTc-maraciclatide imaging and clinical and serological markers of disease activity
  intervention type: Radiation
  intervention name: 99mMaracticaltide imaging
  description: 7.3.1 99mTc-maraciclatide imaging This will be undertaken at baseline and optionally at 8-12 weeks. Not more than 75 µg of 99mTc-maraciclatide will be administered intravenously with an activity as close as possible to 740 MBq. Static whole-body imaging will be undertaken after a maximum of 2 hours with further dedicated views of the hands and feet. Total image acquisition time will be approximately 30 minutes. Images will be scored by quantitative and semi-quantitative methods by a blinded observer.
  Additional study bloods (20ml) will be taken at baseline and 6-month visits for serological
        markers of inflammation and neoangiogenesis. Serum samples will be given a trial ID and
        stored in the Infectious Disease Biobank, King's College London. Samples will be processed,
        stored and disposed in accordance with all applicable legal and regulatory requirements,
        including the Human Tissue Act 2004 and any amendments thereafter.
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  responsible party type: Sponsor
  mesh term: Arthritis
  mesh term: Arthritis, Rheumatoid
  sharing ipd: No