<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/NCT04429776</url>
  </required_header>
  <id_info>
    <org_study_id>281569</org_study_id>
    <nct_id>NCT04429776</nct_id>
  </id_info>
  <brief_title>Tapering of Biologics in Inflammatory Arthritis Patients in Remission</brief_title>
  <acronym>TAPER</acronym>
  <official_title>Tapering of Biologics in Inflammatory Arthritis Patients in Remission</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Manchester</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Manchester</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>
      Rheumatoid arthritis (RA) and Psoriatic Arthritis (PsA) are types of inflammatory arthritis.&#xD;
      They are disabling conditions caused by inflammation in joints that can lead to pain,&#xD;
      stiffness, fatigue and joint damage. There is currently no cure but treatment is aimed at&#xD;
      reducing joint inflammation. Some of the most promising new therapies work by interfering&#xD;
      with the binding of a molecule called tumour necrosis factor (TNF). In recent years, new&#xD;
      anti-TNF drugs (such as adalimumab, etanercept and certolizumab) have been developed that&#xD;
      block the action of TNF and reduce this inflammation. These drugs are very effective in&#xD;
      controlling inflammation for many patients whose arthritis has not responded to other&#xD;
      therapies. Some patients can take these medications for a long time. If a patient is stable&#xD;
      on their rheumatoid arthritis biologic or biosimilar, tapering the drug is often considered.&#xD;
&#xD;
      The investigators are planning to look at drug level and anti-drug antibody testing to guide&#xD;
      anti-TNF tapering (reducing) decisions in UK patients with RA who have stable, reduced&#xD;
      arthritis symptoms. The investigators think that measuring these drug levels and anti-drug&#xD;
      antibodies in blood samples will be useful for guiding this process, but the investigators&#xD;
      can't be sure. It is important to do this safely so the patient doesn't experience a flare of&#xD;
      their disease symptoms. The study will be used to determine whether a much larger study to&#xD;
      assess the usefulness of these measurements would be achievable.&#xD;
&#xD;
      This study will assess whether measuring biomarkers (measurable substances in the blood) that&#xD;
      may affect a patient's response to treatment.&#xD;
&#xD;
      If a patient are eligible to take part, they will be randomly allocated to one of the&#xD;
      following groups;&#xD;
&#xD;
        -  Their Doctor receiving information and treatment advice based on their blood results or&#xD;
&#xD;
        -  Their Doctor not receiving this information&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants will be randomly allocated to feedback of their drug levels / antidrug antibody&#xD;
      status to their consultant prior to tapering, or not, in a 1:1 ratio.&#xD;
&#xD;
        -  Those participants randomised to the group where no feedback is required will have their&#xD;
           dosing interval doubled (from 2 to 4 weeks for certolizumab and adalimumab; from 1 to 2&#xD;
           weeks for etanercept).&#xD;
&#xD;
        -  For participants randomised to the arm where results are received by the treating&#xD;
           clinician, advice will accompany the results. It will be made clear that this is advice&#xD;
           only and that the ultimate treatment decisions rest with the treating clinician.&#xD;
&#xD;
      Patients would be recruited at the point at which the decision is made to begin tapering&#xD;
      their biologic.&#xD;
&#xD;
      The NHS site teams will be informed which arm of the study the participant has been&#xD;
      randomised to, as they will be made aware of patient test results. Participants will not be&#xD;
      blinded to which intervention they receive. University of Manchester Researchers undertaking&#xD;
      the laboratory tests and those entering study data will be blinded.&#xD;
&#xD;
      The consent form, registration form, baseline CRF and baseline participant questionnaire&#xD;
      should then be returned to the study coordinator at CfMR in the pre-paid packaging provided.&#xD;
&#xD;
      A baseline DAS28 score must be provided. This should be from no more than a month before the&#xD;
      date of consent. If this cannot be provided the patient is not eligible to take part.&#xD;
&#xD;
      Recruiting teams can start to taper the patient's medication immediately after consent on to&#xD;
      the TAPER trial.&#xD;
&#xD;
      Blood samples will be taken at the following time points;&#xD;
&#xD;
        -  Baseline (at the point of consent, when the decision to taper is made)&#xD;
&#xD;
        -  6 months after tapering starts&#xD;
&#xD;
        -  12 months after tapering starts Participants in TAPER will need to have their blood&#xD;
           samples taken the day before their next anti-TNF injection date. This means the&#xD;
           participant will have to come in to their hospital sites at these time points for their&#xD;
           sample. Sites will be provided with blood kits for this. These will include a phlebotomy&#xD;
           letter, just in case the participant needs to go to a different hospital department to&#xD;
           have their bloods taken. These will be returned to the University of Manchester is the&#xD;
           pre-paid postage boxes provided.&#xD;
&#xD;
      The researchers would like each of the follow-up visits to occur as closely to the 6 month&#xD;
      and 12 month time points as possible. However, the researchers will accept the following&#xD;
      visit windows;&#xD;
&#xD;
      • 6 and 12 month time points; +/- 1 month The University of Manchester will return the blood&#xD;
      results to site for participants randomised to the arm where results are returned. This will&#xD;
      be sent via email with appropriate treatment advice, as per the information in section 4&#xD;
      within 4 weeks of sample receipt. The site team will receive these results by letter in&#xD;
      advance of the follow-up visit and will have the opportunity to discuss these with the Chief&#xD;
      Investigator, Prof. Anne Barton, in advance of the visit if required. For participants in the&#xD;
      control arm (no feedback of results), the blood samples will be collected and tested in the&#xD;
      same way but results will not be provided to the treating clinician.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">October 1, 2020</start_date>
  <completion_date type="Anticipated">October 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>50 Participants: randomised 1:1 to either feedback of test results to treating clinician or no feedback to treating clinician (25 participants each arm)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to flare</measure>
    <time_frame>3 years</time_frame>
    <description>Time to flare</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Successful recruitment</measure>
    <time_frame>3 years</time_frame>
    <description>Successful recruitment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Was biologic advice, provided in the protocol, adopted by clinicians and participants?</measure>
    <time_frame>3 years</time_frame>
    <description>Adoption of biologic advice by clinicians and participants; assessed by end of study questionnaires</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participant withdrawal rate</measure>
    <time_frame>3 years</time_frame>
    <description>Participant withdrawal rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participant acceptability, via the feedback form</measure>
    <time_frame>3 years</time_frame>
    <description>Participant acceptability, via the feedback form</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participant reported outcome measures recorded in the participant questionnaire booklet.</measure>
    <time_frame>3 years</time_frame>
    <description>Participant reported outcome measures recorded in the participant questionnaire booklet.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <condition>Psoriatic Arthritis</condition>
  <arm_group>
    <arm_group_label>Feedback Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Trough blood samples taken and analysed at baseline, 6m and 12m. Results fed back to recruiting clinical team who can choose to use these to influence their tapering decisions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Feedback Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Trough blood samples taken and analysed at baseline, 6m and 12m. Results not fed back to recruiting clinical team.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Drug level testing</intervention_name>
    <description>These will be carried out at the CfMR labs at the University of Manchester.</description>
    <arm_group_label>Feedback Arm</arm_group_label>
    <arm_group_label>No Feedback Arm</arm_group_label>
    <other_name>Anti-drug antibody testing</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must have RA according to the American College of Rheumatology (ACR) 1987 or&#xD;
             2010 criteria&#xD;
&#xD;
          2. Patients must be willing and able to participate in the study (including follow up&#xD;
             visits and providing blood samples) after providing informed consent.&#xD;
&#xD;
          3. Patients must currently be on stable treatment a one of the following single anti-TNF&#xD;
             agents Adalimumab, Etanercept or Certolizumab. They must have been taking this&#xD;
             biologic/ biosimilar therapy for a minimum of 12 months&#xD;
&#xD;
          4. Patients must be in remission with a DAS28 CRP of less than or equal to 2.6.&#xD;
&#xD;
          5. A DAS28 score must be provided at baseline. This must have been taken within the month&#xD;
             before study recruitment. If this DAS score is not available, the patient is not&#xD;
             eligible to take part.&#xD;
&#xD;
          6. Consultant must be looking to taper patient's standard care medication&#xD;
&#xD;
          7. Aged 18 years or over&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Anyone who has switched anti-TNF agent in the last 12 months&#xD;
&#xD;
          2. Anyone without a recent DAS score (within the previous month)&#xD;
&#xD;
          3. Anyone taking any anti-TNF therapy that isn't Adalimumab, Etanercept or Certolizumab.&#xD;
&#xD;
          4. Anyone who has received steroids within past 3 months (enteral, parenteral or&#xD;
             intra-articular)&#xD;
&#xD;
          5. Anyone who is currently pregnancy, or pregnancy planned within next 6 months&#xD;
&#xD;
          6. Anyone with any planned major surgery&#xD;
&#xD;
          7. Anyone with the inability to provide informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Anne C Barton, FRCP PhD</last_name>
    <phone>01612760539</phone>
    <email>anne.barton@manchester.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sarah L Ashton</last_name>
    <phone>01612760539</phone>
    <email>sarah.ashton-2@manchester.ac.uk</email>
  </overall_contact_backup>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 5, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>June 9, 2020</last_update_submitted>
  <last_update_submitted_qc>June 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Manchester</investigator_affiliation>
    <investigator_full_name>Anne Barton</investigator_full_name>
    <investigator_title>Clinical Professor of Rheumatology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Psoriatic</mesh_term>
  </condition_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/NCT04429776
org study id: 281569
nct id: NCT04429776
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Rheumatoid arthritis (RA) and Psoriatic Arthritis (PsA) are types of inflammatory arthritis.
      They are disabling conditions caused by inflammation in joints that can lead to pain,
      stiffness, fatigue and joint damage. There is currently no cure but treatment is aimed at
      reducing joint inflammation. Some of the most promising new therapies work by interfering
      with the binding of a molecule called tumour necrosis factor (TNF). In recent years, new
      anti-TNF drugs (such as adalimumab, etanercept and certolizumab) have been developed that
      block the action of TNF and reduce this inflammation. These drugs are very effective in
      controlling inflammation for many patients whose arthritis has not responded to other
      therapies. Some patients can take these medications for a long time. If a patient is stable
      on their rheumatoid arthritis biologic or biosimilar, tapering the drug is often considered.

      The investigators are planning to look at drug level and anti-drug antibody testing to guide
      anti-TNF tapering (reducing) decisions in UK patients with RA who have stable, reduced
      arthritis symptoms. The investigators think that measuring these drug levels and anti-drug
      antibodies in blood samples will be useful for guiding this process, but the investigators
      can't be sure. It is important to do this safely so the patient doesn't experience a flare of
      their disease symptoms. The study will be used to determine whether a much larger study to
      assess the usefulness of these measurements would be achievable.

      This study will assess whether measuring biomarkers (measurable substances in the blood) that
      may affect a patient's response to treatment.

      If a patient are eligible to take part, they will be randomly allocated to one of the
      following groups;

        -  Their Doctor receiving information and treatment advice based on their blood results or

        -  Their Doctor not receiving this information
Participants will be randomly allocated to feedback of their drug levels / antidrug antibody
      status to their consultant prior to tapering, or not, in a 1:1 ratio.

        -  Those participants randomised to the group where no feedback is required will have their
           dosing interval doubled (from 2 to 4 weeks for certolizumab and adalimumab; from 1 to 2
           weeks for etanercept).

        -  For participants randomised to the arm where results are received by the treating
           clinician, advice will accompany the results. It will be made clear that this is advice
           only and that the ultimate treatment decisions rest with the treating clinician.

      Patients would be recruited at the point at which the decision is made to begin tapering
      their biologic.

      The NHS site teams will be informed which arm of the study the participant has been
      randomised to, as they will be made aware of patient test results. Participants will not be
      blinded to which intervention they receive. University of Manchester Researchers undertaking
      the laboratory tests and those entering study data will be blinded.

      The consent form, registration form, baseline CRF and baseline participant questionnaire
      should then be returned to the study coordinator at CfMR in the pre-paid packaging provided.

      A baseline DAS28 score must be provided. This should be from no more than a month before the
      date of consent. If this cannot be provided the patient is not eligible to take part.

      Recruiting teams can start to taper the patient's medication immediately after consent on to
      the TAPER trial.

      Blood samples will be taken at the following time points;

        -  Baseline (at the point of consent, when the decision to taper is made)

        -  6 months after tapering starts

        -  12 months after tapering starts Participants in TAPER will need to have their blood
           samples taken the day before their next anti-TNF injection date. This means the
           participant will have to come in to their hospital sites at these time points for their
           sample. Sites will be provided with blood kits for this. These will include a phlebotomy
           letter, just in case the participant needs to go to a different hospital department to
           have their bloods taken. These will be returned to the University of Manchester is the
           pre-paid postage boxes provided.

      The researchers would like each of the follow-up visits to occur as closely to the 6 month
      and 12 month time points as possible. However, the researchers will accept the following
      visit windows;

      • 6 and 12 month time points; +/- 1 month The University of Manchester will return the blood
      results to site for participants randomised to the arm where results are returned. This will
      be sent via email with appropriate treatment advice, as per the information in section 4
      within 4 weeks of sample receipt. The site team will receive these results by letter in
      advance of the follow-up visit and will have the opportunity to discuss these with the Chief
      Investigator, Prof. Anne Barton, in advance of the visit if required. For participants in the
      control arm (no feedback of results), the blood samples will be collected and tested in the
      same way but results will not be provided to the treating clinician.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 50 Participants: randomised 1:1 to either feedback of test results to treating clinician or no feedback to treating clinician (25 participants each arm)
primary purpose: Treatment
masking: None (Open Label)
measure: Time to flare
time frame: 3 years
description: Time to flare
measure: Successful recruitment
time frame: 3 years
description: Successful recruitment
measure: Was biologic advice, provided in the protocol, adopted by clinicians and participants?
time frame: 3 years
description: Adoption of biologic advice by clinicians and participants; assessed by end of study questionnaires
measure: Participant withdrawal rate
time frame: 3 years
description: Participant withdrawal rate
measure: Participant acceptability, via the feedback form
time frame: 3 years
description: Participant acceptability, via the feedback form
measure: Participant reported outcome measures recorded in the participant questionnaire booklet.
time frame: 3 years
description: Participant reported outcome measures recorded in the participant questionnaire booklet.
arm group label: Feedback Arm
arm group type: Experimental
description: Trough blood samples taken and analysed at baseline, 6m and 12m. Results fed back to recruiting clinical team who can choose to use these to influence their tapering decisions.
arm group label: No Feedback Arm
arm group type: Active Comparator
description: Trough blood samples taken and analysed at baseline, 6m and 12m. Results not fed back to recruiting clinical team.
intervention type: Diagnostic Test
intervention name: Drug level testing
description: These will be carried out at the CfMR labs at the University of Manchester.
arm group label: Feedback Arm
arm group label: No Feedback Arm
other name: Anti-drug antibody testing
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anne C Barton, FRCP PhD
phone: 01612760539
email: anne.barton@manchester.ac.uk
last name: Sarah L Ashton
phone: 01612760539
email: sarah.ashton-2@manchester.ac.uk
responsible party type: Principal Investigator
investigator affiliation: University of Manchester
investigator full name: Anne Barton
investigator title: Clinical Professor of Rheumatology
mesh term: Arthritis
mesh term: Arthritis, Psoriatic
sharing ipd: No