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/NCT06037811</url>
    </required_header>
    <id_info>
      <org_study_id>ADA2023</org_study_id>
      <nct_id>NCT06037811</nct_id>
    </id_info>
    <brief_title>Early Adalimumab Induction for Immune Checkpoint Inhibitor Associated Inflammatory Arthritis</brief_title>
    <official_title>Early Adalimumab Induction for Treatment of Steroid Dependent Immune Checkpoint Inhibitor Associated Inflammatory Arthritis: A Pragmatic Randomized Clinical Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Tom Appleton</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Canadian Research Group in Immuno-Oncology</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Western University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Lawson Health Research Institute</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study will examine the effectiveness of administering adalimumab as a treatment for&#xD;
        patients in the early stages of steroid-dependent immune checkpoint Inhibitor associated&#xD;
        inflammatory arthritis (ir-IA). Adalimumab (ADA) is a TNF inhibitor (TNFi) that is well&#xD;
        established as a standard of care treatment for numerous types of inflammatory arthritis. It&#xD;
        is hoped that adalimumab at the early stages of the ir-IA will reduce the symptoms and&#xD;
        therefore reduce the need for steroids. This study is a pragmatic randomized clinical trial.&#xD;
        Patients will be randomized 1:1 to each treatment group. To evaluate the steroid sparing&#xD;
        effect of early induction six doses of Adalimumab will be administered to patients in the&#xD;
        study treatment arm as compared to the usual standard of care of a predefined corticosteroid&#xD;
        regimen and taper at 12 weeks administered in the control group.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 2023</start_date>
    <completion_date type="Anticipated">November 2025</completion_date>
    <primary_completion_date type="Anticipated">August 2025</primary_completion_date>
    <phase>Phase 2</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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>percentage of participants on prednisone</measure>
      <time_frame>at 12 weeks</time_frame>
      <description>Definition of success: Thirty percent fewer participants on prednisone in Group 2 vs Group 1.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Cumulative prednisone dose</measure>
      <time_frame>at 12 weeks</time_frame>
      <description>Definition of success: Thirty percent reduction in the cumulative dose of steroids in Group 2 compared to Group 1.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>percentage of participants on prednisone</measure>
      <time_frame>24 weeks</time_frame>
      <description>Definition of success: Thirty percent difference between the two groups</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cumulative prednisone dose</measure>
      <time_frame>24 weeks</time_frame>
      <description>Definition of success: Thirty percent difference between the two groups</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>percentage of dose reduction of prednisone</measure>
      <time_frame>At 12 and 24 weeks</time_frame>
      <description>Definition of success: Thirty percent difference between the two groups</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>percentage of participants with immune-related inflammatory arthritis in remission (based on opinion of investigator)</measure>
      <time_frame>at 12 and 24 weeks</time_frame>
      <description>Definition of success: Thirty percent difference between the two groups</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>percentage of participants with immune-related inflammatory arthritis resolution (based on opinion of investigator)</measure>
      <time_frame>at 12 and 24 weeks</time_frame>
      <description>Definition of success: Thirty percent difference between the two groups</description>
    </secondary_outcome>
    <other_outcome>
      <measure>percentage of participants with persistent active synovitis/tenosynovitis (yes/no)</measure>
      <time_frame>at 12 and 24 weeks</time_frame>
      <description>Differences between treatment groups ≥20% will be considered significant</description>
    </other_outcome>
    <other_outcome>
      <measure>percentage of participants treated with methotrexate and/or hydroxychloroquine</measure>
      <time_frame>at 12 and 24 weeks</time_frame>
      <description>Differences between treatment groups ≥20% will be considered significant</description>
    </other_outcome>
    <other_outcome>
      <measure>MDGA (MD global assessment) of arthritis 0 to 10</measure>
      <time_frame>at weeks 12 and 24</time_frame>
      <description>Differences between treatment groups ≥20% will be considered significant</description>
    </other_outcome>
    <other_outcome>
      <measure>Participant reported pain on a visual analog scale from 0 to 10.</measure>
      <time_frame>at weeks 12 and 24</time_frame>
      <description>Enhancement of quality of life due to ADA will be defined as 50% improvement in any of these readouts in ≥50% of participants at weeks 12 and 24 compared to Group 1.</description>
    </other_outcome>
    <other_outcome>
      <measure>PGA (patient global assessment) of arthritis 0-10</measure>
      <time_frame>at weeks 12 and 24</time_frame>
      <description>Enhancement of quality of life due to ADA will be defined as 50% improvement in any of these readouts in ≥50% of participants at weeks 12 and 24 compared to Group 1.</description>
    </other_outcome>
    <other_outcome>
      <measure>FACIT-F (Functional Assessment of Chronic Illness Therapy-Fatigue Score)</measure>
      <time_frame>at weeks 12 and 24</time_frame>
      <description>Enhancement of quality of life due to ADA will be defined as 50% improvement in any of these readouts in ≥50% of participants at weeks 12 and 24 compared to Group 1.</description>
    </other_outcome>
    <other_outcome>
      <measure>EQ-5D (EuroQol 5 Dimension for evaluation of generic quality of life)</measure>
      <time_frame>at weeks 12 and 24</time_frame>
      <description>Enhancement of quality of life due to ADA will be defined as 50% improvement in any of these readouts in ≥50% of participants at weeks 12 and 24 compared to Group 1.</description>
    </other_outcome>
    <other_outcome>
      <measure>Cancer status vs baseline: overall survival (OS), progression free survival (PFS)</measure>
      <time_frame>at 12 and 24 weeks</time_frame>
      <description>Differences between treatment groups ≥20% will be considered significant</description>
    </other_outcome>
    <other_outcome>
      <measure>Number of participants who continue, hold or stop ICI therapy</measure>
      <time_frame>at 12 and 24 weeks</time_frame>
      <description>Differences between treatment groups ≥20% will be considered significant</description>
    </other_outcome>
    <other_outcome>
      <measure>Feasibility: Number of participating sites; Number of participants screened, consented, randomized, and followed-up at each participating site</measure>
      <time_frame>at week 24</time_frame>
      <description>Differences between treatment groups ≥20% will be considered significant</description>
    </other_outcome>
    <other_outcome>
      <measure>The rates of AEs, serious AEs (according to CTCAE), and clinical laboratory abnormalities</measure>
      <time_frame>at 12 and 24 weeks</time_frame>
      <description>ADA will be considered 'safe' if the frequency of moderate AEs in Group 2 does not exceed 50% (reported rate of moderate AE in RA is 41%)</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Inflammatory Arthritis</condition>
    <condition>Immune-related Adverse Event</condition>
    <arm_group>
      <arm_group_label>Standard of care group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Prednisone 10 mg daily for 2 weeks, then taper by 2.5 mg every 2 weeks until stopped.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Adalimumab group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Adalimumab 40 mg subcutaneous every 2 weeks for 6 doses (12 weeks)&#xD;
  + Prednisone 10 mg daily for 2 weeks, tapering by 2.5 mg every 2 weeks until stopped.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Adalimumab</intervention_name>
      <description>Participants will be randomized 1:1 (non-blinded) to receive either adalimumab (40 mg subcutaneous every 2 weeks for 12 weeks) and prednisone vs prednisone alone. Addition of methotrexate (MTX) and/or hydroxychloroquine (HCQ) is permitted, as needed, at the discretion of the treating rheumatologist. No additional conventional synthetic, targeted synthetic or biologic DMARDs are permitted during the trial.</description>
      <arm_group_label>Adalimumab group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Prednisone</intervention_name>
      <description>Prednisone as per standard of care.</description>
      <arm_group_label>Adalimumab group</arm_group_label>
      <arm_group_label>Standard of care group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  • Patients are deemed eligible for study participation if they meet all the following:&#xD;
  &#xD;
                 -  Adult patients (age 18 or older)&#xD;
  &#xD;
                 -  New (within the last 6 months prior to enrollment) inflammatory arthritis defined&#xD;
                    by any of the following at the time of screening (either on physical exam or by&#xD;
                    ultrasound) by a certified rheumatologist:&#xD;
  &#xD;
            -  1 or more swollen joints OR&#xD;
  &#xD;
            -  1 or more tenosynovitis OR&#xD;
  &#xD;
            -  1 or more enthesitis&#xD;
  &#xD;
                 -  Arthritis onset with taking ICI therapy OR within 4 weeks of stopping ICI therapy&#xD;
                    including CTLA-4, PD-1, and PDL-1 inhibitors&#xD;
  &#xD;
                 -  Initiation of ICI therapy must predate the onset of inflammatory arthritis&#xD;
  &#xD;
                 -  Arthritis either does not respond completely to prednisone doses of 10mg&#xD;
                    (equivalent) OR recurs with prednisone taper below 10mg daily.&#xD;
  &#xD;
                 -  Negative tuberculosis (TB) status within the past 12 months (TB skin test or&#xD;
                    quantiferon) for the patients in the adalimumab group. If not available, the&#xD;
                    status should be confirmed within 6 months of enrollment in the study (adalimumab&#xD;
                    group only)&#xD;
  &#xD;
                 -  Written informed consent provided by patient or power of attorney&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients are excluded if they meet any of the following:&#xD;
  &#xD;
            -  Previous diagnosis of inflammatory arthritis or other rheumatic disease (prior to&#xD;
               current acute episode)&#xD;
  &#xD;
                 -  Including but not limited to: rheumatoid arthritis, systemic lupus erythematosus,&#xD;
                    systemic sclerosis, Sjogren's syndrome, psoriatic arthritis, reactive arthritis,&#xD;
                    ankylosing spondylitis, systemic vasculitis, undifferentiated inflammatory&#xD;
                    arthritis, undifferentiated connective tissue disease&#xD;
  &#xD;
            -  Tenosynovitis, synovitis or enthesitis attributed to another cause, fracture or acute&#xD;
               gout/CPPD flare.&#xD;
  &#xD;
            -  Presence of a contraindication to adalimumab therapy&#xD;
  &#xD;
                 -  Any of the following in the 7 days prior to initiation of adalimumab: positive&#xD;
                    tuberculin skin test (&gt;5mm induration within 48 to 72 hours) or positive&#xD;
                    quantiferon, evidence of untreated active infection including fungal infection,&#xD;
                    opportunistic infection, hepatitis B/C, or HIV&#xD;
  &#xD;
                 -  Personal history of congestive heart failure&#xD;
  &#xD;
                 -  Personal or family history of demyelinating neurologic disease&#xD;
  &#xD;
            -  History of previous TNF inhibitor use&#xD;
  &#xD;
            -  Current use of other disease modifying agents including: Chloroquine, Sulfasalazine,&#xD;
               Azathioprine, 6-MP, and Leflunomide&#xD;
  &#xD;
            -  Presence of a concomitant non-rheumatic irAE which required systemic immunosuppression&#xD;
               within the past 3 months e.g. pneumonitis, hepatitis, colitis, scleritis, nephritis&#xD;
  &#xD;
            -  Require chronic steroid treatment for adrenal insufficiency or another medical reason&#xD;
               other than ir-IA&#xD;
  &#xD;
            -  Pregnancy, breastfeeding or childbearing potential without practicing highly effective&#xD;
               contraception.&#xD;
  &#xD;
            -  Inability to participate in follow-up visits&#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>Tom Appleton, MD, PhD, FRCPC</last_name>
      <phone>519-646-6100</phone>
      <email>tom.appelton@sjhc.london.on.ca</email>
    </overall_contact>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 31, 2023</study_first_submitted>
    <study_first_submitted_qc>September 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 14, 2023</study_first_posted>
    <last_update_submitted>September 13, 2023</last_update_submitted>
    <last_update_submitted_qc>September 13, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Lawson Health Research Institute</investigator_affiliation>
      <investigator_full_name>Tom Appleton</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>Immune Checkpoint Inhibitor</keyword>
    <keyword>Adalimumab</keyword>
    <keyword>TNF-alpha inhibitor</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Arthritis</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Prednisone</mesh_term>
      <mesh_term>Adalimumab</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</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/NCT06037811
  org study id: ADA2023
  nct id: NCT06037811
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  This study will examine the effectiveness of administering adalimumab as a treatment for
        patients in the early stages of steroid-dependent immune checkpoint Inhibitor associated
        inflammatory arthritis (ir-IA). Adalimumab (ADA) is a TNF inhibitor (TNFi) that is well
        established as a standard of care treatment for numerous types of inflammatory arthritis. It
        is hoped that adalimumab at the early stages of the ir-IA will reduce the symptoms and
        therefore reduce the need for steroids. This study is a pragmatic randomized clinical trial.
        Patients will be randomized 1:1 to each treatment group. To evaluate the steroid sparing
        effect of early induction six doses of Adalimumab will be administered to patients in the
        study treatment arm as compared to the usual standard of care of a predefined corticosteroid
        regimen and taper at 12 weeks administered in the control group.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: percentage of participants on prednisone
  time frame: at 12 weeks
  description: Definition of success: Thirty percent fewer participants on prednisone in Group 2 vs Group 1.
  measure: Cumulative prednisone dose
  time frame: at 12 weeks
  description: Definition of success: Thirty percent reduction in the cumulative dose of steroids in Group 2 compared to Group 1.
  measure: percentage of participants on prednisone
  time frame: 24 weeks
  description: Definition of success: Thirty percent difference between the two groups
  measure: Cumulative prednisone dose
  time frame: 24 weeks
  description: Definition of success: Thirty percent difference between the two groups
  measure: percentage of dose reduction of prednisone
  time frame: At 12 and 24 weeks
  description: Definition of success: Thirty percent difference between the two groups
  measure: percentage of participants with immune-related inflammatory arthritis in remission (based on opinion of investigator)
  time frame: at 12 and 24 weeks
  description: Definition of success: Thirty percent difference between the two groups
  measure: percentage of participants with immune-related inflammatory arthritis resolution (based on opinion of investigator)
  time frame: at 12 and 24 weeks
  description: Definition of success: Thirty percent difference between the two groups
  measure: percentage of participants with persistent active synovitis/tenosynovitis (yes/no)
  time frame: at 12 and 24 weeks
  description: Differences between treatment groups ≥20% will be considered significant
  measure: percentage of participants treated with methotrexate and/or hydroxychloroquine
  time frame: at 12 and 24 weeks
  description: Differences between treatment groups ≥20% will be considered significant
  measure: MDGA (MD global assessment) of arthritis 0 to 10
  time frame: at weeks 12 and 24
  description: Differences between treatment groups ≥20% will be considered significant
  measure: Participant reported pain on a visual analog scale from 0 to 10.
  time frame: at weeks 12 and 24
  description: Enhancement of quality of life due to ADA will be defined as 50% improvement in any of these readouts in ≥50% of participants at weeks 12 and 24 compared to Group 1.
  measure: PGA (patient global assessment) of arthritis 0-10
  time frame: at weeks 12 and 24
  description: Enhancement of quality of life due to ADA will be defined as 50% improvement in any of these readouts in ≥50% of participants at weeks 12 and 24 compared to Group 1.
  measure: FACIT-F (Functional Assessment of Chronic Illness Therapy-Fatigue Score)
  time frame: at weeks 12 and 24
  description: Enhancement of quality of life due to ADA will be defined as 50% improvement in any of these readouts in ≥50% of participants at weeks 12 and 24 compared to Group 1.
  measure: EQ-5D (EuroQol 5 Dimension for evaluation of generic quality of life)
  time frame: at weeks 12 and 24
  description: Enhancement of quality of life due to ADA will be defined as 50% improvement in any of these readouts in ≥50% of participants at weeks 12 and 24 compared to Group 1.
  measure: Cancer status vs baseline: overall survival (OS), progression free survival (PFS)
  time frame: at 12 and 24 weeks
  description: Differences between treatment groups ≥20% will be considered significant
  measure: Number of participants who continue, hold or stop ICI therapy
  time frame: at 12 and 24 weeks
  description: Differences between treatment groups ≥20% will be considered significant
  measure: Feasibility: Number of participating sites; Number of participants screened, consented, randomized, and followed-up at each participating site
  time frame: at week 24
  description: Differences between treatment groups ≥20% will be considered significant
  measure: The rates of AEs, serious AEs (according to CTCAE), and clinical laboratory abnormalities
  time frame: at 12 and 24 weeks
  description: ADA will be considered 'safe' if the frequency of moderate AEs in Group 2 does not exceed 50% (reported rate of moderate AE in RA is 41%)
  arm group label: Standard of care group
  arm group type: Active Comparator
  description: Prednisone 10 mg daily for 2 weeks, then taper by 2.5 mg every 2 weeks until stopped.
  arm group label: Adalimumab group
  arm group type: Active Comparator
  description: Adalimumab 40 mg subcutaneous every 2 weeks for 6 doses (12 weeks)
  + Prednisone 10 mg daily for 2 weeks, tapering by 2.5 mg every 2 weeks until stopped.
  intervention type: Drug
  intervention name: Adalimumab
  description: Participants will be randomized 1:1 (non-blinded) to receive either adalimumab (40 mg subcutaneous every 2 weeks for 12 weeks) and prednisone vs prednisone alone. Addition of methotrexate (MTX) and/or hydroxychloroquine (HCQ) is permitted, as needed, at the discretion of the treating rheumatologist. No additional conventional synthetic, targeted synthetic or biologic DMARDs are permitted during the trial.
  arm group label: Adalimumab group
  intervention type: Drug
  intervention name: Prednisone
  description: Prednisone as per standard of care.
  arm group label: Adalimumab group
  arm group label: Standard of care group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Tom Appleton, MD, PhD, FRCPC
  phone: 519-646-6100
  email: tom.appelton@sjhc.london.on.ca
  responsible party type: Sponsor-Investigator
  investigator affiliation: Lawson Health Research Institute
  investigator full name: Tom Appleton
  investigator title: Principal Investigator
  mesh term: Arthritis
  mesh term: Prednisone
  mesh term: Adalimumab
  sharing ipd: Undecided