<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/NCT03816397</url>
  </required_header>
  <id_info>
    <org_study_id>17-23987</org_study_id>
    <secondary_id>UG1EY029658</secondary_id>
    <nct_id>NCT03816397</nct_id>
  </id_info>
  <brief_title>Adalimumab in JIA-associated Uveitis Stopping Trial</brief_title>
  <acronym>ADJUST</acronym>
  <official_title>Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nisha Acharya</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Children's Hospital of Philadelphia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Mercy Hospital Kansas City</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Eye Institute (NEI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Great Ormond Street Hospital for Children NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospitals Bristol and Weston NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Alder Hey Children's NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Newcastle-upon-Tyne Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sheffield Children's NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cambridge University Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Royal Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Norfolk and Norwich University Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of California, Davis</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Texas at Austin</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Miami</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospitals, Leicester</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Colorado Retina Associates</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Manchester University NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The proposed study is a stratified, block-randomized, double-masked, controlled trial to&#xD;
      determine the feasibility of discontinuing adalimumab treatment in patients with quiescent&#xD;
      uveitis associated with juvenile idiopathic arthritis (JIA) or chronic anterior uveitis&#xD;
      (CAU).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Juvenile idiopathic arthritis (JIA)-associated uveitis is a chronic pediatric&#xD;
      ocular inflammatory condition that can result in visual impairment. Chronic anterior uveitis&#xD;
      (CAU) does not have systemic manifestations of disease but presents similarly in the eye and&#xD;
      can result in identical visual complications as JIA-associated uveitis. Adalimumab, a tumor&#xD;
      necrosis factor (TNF)-alpha inhibitor, effectively controls joint and eye inflammation;&#xD;
      however, its long-term use may increase the risk of adverse health outcomes and place an&#xD;
      undue financial burden on the patient and healthcare system given its high cost. There is&#xD;
      great interest for patients to stop adalimumab following remission due to these reasons but&#xD;
      there is a lack of information on the ability to maintain control after discontinuing&#xD;
      adalimumab.&#xD;
&#xD;
      Methods: The Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Trial (ADJUST) is&#xD;
      a multi-center international trial that will randomize 118 participants aged 2 years and&#xD;
      older with controlled JIA-associated uveitis or chronic anterior uveitis to either continue&#xD;
      adalimumab or discontinue adalimumab and receive a placebo. The trial will compare the time&#xD;
      to uveitis recurrence between the two groups over 12 months. All participants will receive&#xD;
      the standard weight-based dose of adalimumab or placebo: 20 mg biweekly (if &lt; 30 kg) or 40 mg&#xD;
      biweekly (if ≥ 30 kg).&#xD;
&#xD;
      Impact: This is the first randomized controlled trial to assess the efficacy of discontinuing&#xD;
      adalimumab after demonstrating control of JIA-associated uveitis for at least 12 months. The&#xD;
      results of ADJUST will provide information on clinical outcomes to guide clinicians in their&#xD;
      decision-making regarding discontinuation of adalimumab.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 15, 2020</start_date>
  <completion_date type="Anticipated">July 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2025</primary_completion_date>
  <phase>Phase 4</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to treatment failure</measure>
    <time_frame>From baseline until 12 months post-randomization</time_frame>
    <description>Time to treatment failure until 12 months post-randomization. Treatment failure is defined by recurrence of ocular inflammation in at least one eye as follows:&#xD;
3+ anterior chamber (AC) for a single visit&#xD;
•&gt;0.5+ anterior chamber (AC) cell for ≥28 days&#xD;
2-step increase in AC cell observed at two separate visits ≥7 days apart&#xD;
0.5+ vitreous haze, active retinal or choroidal inflammation, or macular edema observed at a single visit. Treatment failure can also be declared by recurrence of joint inflammation that is persistent and severe enough to necessitate unmasking to manage the arthritis recurrence.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">118</enrollment>
  <condition>Uveitis</condition>
  <condition>JIA</condition>
  <arm_group>
    <arm_group_label>Continue adalimumab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients randomized to this arm will continue adalimumab at their current dose (either 20mg/0.2mL or 40mg/0.4mL) administered subcutaneously every other week.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stop adalimumab</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients randomized to this arm will receive a volume-matched placebo (0.8mL) administered subcutaneously every other week.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Adalimumab</intervention_name>
    <description>Adalimumab is a fully human monoclonal anti-tumor necrosis factor alpha antibody, a biologic, immunomodulatory drug. Adalimumab 20mg/0.8mL and 40mg/0.8mL is a clear, colorless solution provided in a pre-filled syringe for subcutaneous injection. The formulation is adalimumab, mannitol, polysorbate 80, and water for injection Each pre-filled syringe has a fixed 29-gauge thin wall and ½ inch needle with black protective cover and is intended for a single dose to a single patient.</description>
    <arm_group_label>Continue adalimumab</arm_group_label>
    <other_name>HUMIRA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The placebo solution is a clear, colorless solution provided in a single-use, pre-filled syringe for subcutaneous injection. The placebo is designed to match the characteristics of the citrate-free adalimumab during injection.</description>
    <arm_group_label>Stop adalimumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria (must meet all of the following to qualify):&#xD;
&#xD;
          -  Stated willingness to comply with all study procedures and availability for the&#xD;
             duration of the study period&#xD;
&#xD;
          -  ≥ 2 years of age&#xD;
&#xD;
          -  History of JIA or CAU diagnosed prior to 16 years of age (patient may be older than 16&#xD;
             at time of enrollment)&#xD;
&#xD;
          -  Formal diagnosis of JIA-associated uveitis or CAU with no other suspected etiology&#xD;
&#xD;
          -  ≥12 consecutive months of controlled ocular inflammation (≤0.5+ anterior chamber cell,&#xD;
             ≤0.5+ vitreous haze, no active retinal/choroidal lesions in either eye)&#xD;
&#xD;
          -  ≥ 12 consecutive months of controlled arthritis verified by a pediatric&#xD;
             rheumatologist, if defined as JIA-associated uveitis&#xD;
&#xD;
          -  ≥12 consecutive months of treatment with adalimumab or a biosimilar of adalimumab&#xD;
&#xD;
          -  ≥180 days on a stable dose of adalimumab or a biosimilar; must be biweekly dose of&#xD;
             either 20mg (if&lt;30kg) or 40mg (if ≥30kg)&#xD;
&#xD;
          -  If on a biosimilar of adalimumab, ≥90 days on the biosimilar&#xD;
&#xD;
          -  If on concomitant antimetabolite (injectable or oral methotrexate, mycophenolate&#xD;
             mofetil, azathioprine, or leflunomide), dose must be ≤25 mg weekly for methotrexate,&#xD;
             ≤3 g daily for mycophenolate mofetil, ≤250 mg daily for azathioprine, or ≤20 mg daily&#xD;
             for leflunomide; dose and route of administration must be stable for ≥90 days&#xD;
&#xD;
          -  If on topical corticosteroids, dose must be ≤2 drops prednisolone acetate 1% or&#xD;
             equivalent per day and stable for ≥90 days&#xD;
&#xD;
          -  Willingness to limit consumption of alcohol during the study period&#xD;
&#xD;
          -  Agreement to avoid live attenuated vaccinations&#xD;
&#xD;
          -  Agreement to use highly effective contraception for ≥28 days prior to screening and&#xD;
             throughout study period (for males and females of reproductive age)&#xD;
&#xD;
          -  Suitable, in the opinion of the Investigator, to continue treatment with adalimumab or&#xD;
             placebo per regional labeling&#xD;
&#xD;
          -  No contraindications to receive adalimumab as per the local Summary of Product&#xD;
             Characteristics (SmPC)&#xD;
&#xD;
        Exclusion Criteria (any one of these excludes the patient):&#xD;
&#xD;
          -  Intraocular surgery in the past 90 days or planned surgery in the next 12 months&#xD;
&#xD;
          -  Severe cataract or opacity preventing view to the posterior pole in both eyes&#xD;
&#xD;
          -  Chronic hypotony (&lt;5mmHg for ≥90 days) in either eye&#xD;
&#xD;
          -  Treatment with oral corticosteroids or intraocular corticosteroid injection within the&#xD;
             last 12 months&#xD;
&#xD;
          -  Use of NSAID eye drops within the last 90 days&#xD;
&#xD;
          -  Acute anterior uveitis characterized by redness and symptoms, including but not&#xD;
             limited to floaters, pain, and light sensitivity&#xD;
&#xD;
          -  Pregnancy or lactation (a pregnancy test will be conducted at baseline and all&#xD;
             follow-up visits for females of reproductive age)&#xD;
&#xD;
          -  Presence of intraretinal or subretinal fluid in either eye&#xD;
&#xD;
          -  Prior safety or tolerability issues with adalimumab&#xD;
&#xD;
          -  History of cancer, active tuberculosis, or hepatitis B&#xD;
&#xD;
          -  Other medical condition expected to dictate treatment course during the study&#xD;
&#xD;
          -  Any of the following laboratory test results on their most recent tests within the&#xD;
             past 90 days prior to screening/enrollment: leukocyte count &lt;2500, platelet count&#xD;
             ≤75000, hemoglobin&lt;9.0, AST or ALT ≥ 2 times the upper limit of normal range,&#xD;
             creatinine ≥1.5&#xD;
&#xD;
        There are no sex, race, or ethnicity restrictions for this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nisha Acharya, MD MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Principal Investigator</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Nisha Acharya, MD MS</last_name>
    <phone>415-476-8131</phone>
    <email>nisha.acharya@ucsf.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of California, Davis</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Parisa Emami-Naeini, MD, MPH</last_name>
    </contact>
    <investigator>
      <last_name>Parisa Emami-Naeini, MD, MPH</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nisha Acharya, MD MS</last_name>
    </contact>
    <investigator>
      <last_name>Nisha Acharya, MD MS</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>John Gonzales, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Thuy Doan, MD PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Colorado Denver</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Katharine Moore, MD</last_name>
    </contact>
    <investigator>
      <last_name>Katharine Moore, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Colorado Retina Associates</name>
      <address>
        <city>Lakewood</city>
        <state>Colorado</state>
        <zip>80228</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mark Dacey, MD</last_name>
    </contact>
    <investigator>
      <last_name>Mark Dacey, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Janet L Davis, MD</last_name>
    </contact>
    <investigator>
      <last_name>Janet L Davis, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's Mercy Hospital</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64108</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Erin Stahl, MD</last_name>
    </contact>
    <investigator>
      <last_name>Erin Stahl, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ashley Cooper, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Virginia Miraldi Utz, MD</last_name>
    </contact>
    <investigator>
      <last_name>Adam Kaufman, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sheila Angeles-Han, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Virginia Miraldi Utz, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stefanie Davidson, MD</last_name>
    </contact>
    <investigator>
      <last_name>Stefanie Davidson, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Melissa Lerman, MD PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37212</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sapna Gangaputra, MD, MPH</last_name>
    </contact>
    <investigator>
      <last_name>Sapna Gangaputra, MD, MPH</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Texas, Austin</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78712</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eric Crowell, MD, MPH</last_name>
    </contact>
    <investigator>
      <last_name>Eric Crowell, MD, MPH</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Utah Health</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Albert Vitale, MD</last_name>
    </contact>
    <investigator>
      <last_name>Albert Vitale, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Aimee Hersh, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Murdoch Children's Research Institute</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3052</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>William Renton</last_name>
      <phone>+61 03 9345 5522</phone>
      <email>william.renton@rch.org.au</email>
    </contact>
    <contact_backup>
      <last_name>Robyn Troutbeck</last_name>
      <phone>+61 04 1160 4664</phone>
      <email>rtroutbeck@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Robyn Troutbeck</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>William Renton</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospitals Bristol and Weston</name>
      <address>
        <city>Bristol</city>
        <zip>BS1 3NU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>A V Ramanan</last_name>
    </contact>
    <investigator>
      <last_name>A V Ramanan</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Andrew Dick</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cambridge University Hospital</name>
      <address>
        <city>Cambridge</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Kate Armon</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Brinda Muthusamy</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospitals, Leicester</name>
      <address>
        <city>Leicester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Arani Sridhar, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Alder Hey Children's Hospital</name>
      <address>
        <city>Liverpool</city>
        <zip>L14 5AB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jose Gonzalez-Martin</last_name>
    </contact>
    <investigator>
      <last_name>Jose Gonzalez-Martin</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Gavin Clearly</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Michael Beresford</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Great Ormond Street Hospital</name>
      <address>
        <city>London</city>
        <zip>WC1N 3JH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elena Moraitis</last_name>
    </contact>
    <investigator>
      <last_name>Elena Moraitis</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Harry Petrushkin</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Manchester University NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jane Ashworth, MD</last_name>
    </contact>
    <investigator>
      <last_name>Jane Ashworth, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Great North Children's Hospital</name>
      <address>
        <city>Newcastle Upon Tyne</city>
        <zip>NE1 4LP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michael Clarke</last_name>
    </contact>
    <investigator>
      <last_name>Michael Clarke</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sharmila Jandial</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Norfolk and Norwich University Hospital</name>
      <address>
        <city>Norwich</city>
        <zip>NR4 6TZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Narman Puvanachandra</last_name>
    </contact>
    <contact_backup>
      <last_name>Louise</last_name>
    </contact_backup>
    <investigator>
      <last_name>Kate Armon</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Narman Puvanachandra</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sheffield Children's Hospital</name>
      <address>
        <city>Sheffield</city>
        <zip>S10 2TQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jessy Choi</last_name>
    </contact>
    <investigator>
      <last_name>Jessy Choi</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Daniel Hawley</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Jaffe GJ, Dick AD, Brezin AP, Nguyen QD, Thorne JE, Kestelyn P, Barisani-Asenbauer T, Franco P, Heiligenhaus A, Scales D, Chu DS, Camez A, Kwatra NV, Song AP, Kron M, Tari S, Suhler EB. Adalimumab in Patients with Active Noninfectious Uveitis. N Engl J Med. 2016 Sep 8;375(10):932-43. doi: 10.1056/NEJMoa1509852.</citation>
    <PMID>27602665</PMID>
  </reference>
  <reference>
    <citation>Nguyen QD, Merrill PT, Jaffe GJ, Dick AD, Kurup SK, Sheppard J, Schlaen A, Pavesio C, Cimino L, Van Calster J, Camez AA, Kwatra NV, Song AP, Kron M, Tari S, Brezin AP. Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet. 2016 Sep 17;388(10050):1183-92. doi: 10.1016/S0140-6736(16)31339-3. Epub 2016 Aug 16. Erratum In: Lancet. 2016 Sep 17;388(10050):1160.</citation>
    <PMID>27542302</PMID>
  </reference>
  <reference>
    <citation>Ramanan AV, Dick AD, Benton D, Compeyrot-Lacassagne S, Dawoud D, Hardwick B, Hickey H, Hughes D, Jones A, Woo P, Edelsten C, Beresford MW; SYCAMORE Trial Management Group. A randomised controlled trial of the clinical effectiveness, safety and cost-effectiveness of adalimumab in combination with methotrexate for the treatment of juvenile idiopathic arthritis associated uveitis (SYCAMORE Trial). Trials. 2014 Jan 9;15:14. doi: 10.1186/1745-6215-15-14.</citation>
    <PMID>24405833</PMID>
  </reference>
  <reference>
    <citation>Vazquez-Cobian LB, Flynn T, Lehman TJ. Adalimumab therapy for childhood uveitis. J Pediatr. 2006 Oct;149(4):572-5. doi: 10.1016/j.jpeds.2006.04.058.</citation>
    <PMID>17011337</PMID>
  </reference>
  <reference>
    <citation>Chang CY, Meyer RM, Reiff AO. Impact of medication withdrawal method on flare-free survival in patients with juvenile idiopathic arthritis on combination therapy. Arthritis Care Res (Hoboken). 2015 May;67(5):658-66. doi: 10.1002/acr.22477.</citation>
    <PMID>25220674</PMID>
  </reference>
  <reference>
    <citation>Baszis K, Garbutt J, Toib D, Mao J, King A, White A, French A. Clinical outcomes after withdrawal of anti-tumor necrosis factor alpha therapy in patients with juvenile idiopathic arthritis: a twelve-year experience. Arthritis Rheum. 2011 Oct;63(10):3163-8. doi: 10.1002/art.30502.</citation>
    <PMID>21702011</PMID>
  </reference>
  <reference>
    <citation>Shakoor A, Esterberg E, Acharya NR. Recurrence of uveitis after discontinuation of infliximab. Ocul Immunol Inflamm. 2014 Apr;22(2):96-101. doi: 10.3109/09273948.2013.812222. Epub 2013 Jul 22.</citation>
    <PMID>23876234</PMID>
  </reference>
  <reference>
    <citation>Acharya NR, Ebert CD, Kelly NK, Porco TC, Ramanan AV, Arnold BF; ADJUST Research Group. Discontinuing adalimumab in patients with controlled juvenile idiopathic arthritis-associated uveitis (ADJUST-Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial): study protocol for a randomised controlled trial. Trials. 2020 Oct 27;21(1):887. doi: 10.1186/s13063-020-04796-z.</citation>
    <PMID>33109240</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 22, 2019</study_first_submitted>
  <study_first_submitted_qc>January 22, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 25, 2019</study_first_posted>
  <last_update_submitted>August 21, 2023</last_update_submitted>
  <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Francisco</investigator_affiliation>
    <investigator_full_name>Nisha Acharya</investigator_full_name>
    <investigator_title>Director, Uveitis and Ocular Inflammatory Disease Service</investigator_title>
  </responsible_party>
  <keyword>chronic anterior uveitis</keyword>
  <keyword>adalimumab</keyword>
  <keyword>JIA-associated uveitis</keyword>
  <keyword>stopping</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uveitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adalimumab</mesh_term>
  </intervention_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/NCT03816397
org study id: 17-23987
secondary id: UG1EY029658
nct id: NCT03816397
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has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The proposed study is a stratified, block-randomized, double-masked, controlled trial to
      determine the feasibility of discontinuing adalimumab treatment in patients with quiescent
      uveitis associated with juvenile idiopathic arthritis (JIA) or chronic anterior uveitis
      (CAU).
Background: Juvenile idiopathic arthritis (JIA)-associated uveitis is a chronic pediatric
      ocular inflammatory condition that can result in visual impairment. Chronic anterior uveitis
      (CAU) does not have systemic manifestations of disease but presents similarly in the eye and
      can result in identical visual complications as JIA-associated uveitis. Adalimumab, a tumor
      necrosis factor (TNF)-alpha inhibitor, effectively controls joint and eye inflammation;
      however, its long-term use may increase the risk of adverse health outcomes and place an
      undue financial burden on the patient and healthcare system given its high cost. There is
      great interest for patients to stop adalimumab following remission due to these reasons but
      there is a lack of information on the ability to maintain control after discontinuing
      adalimumab.

      Methods: The Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Trial (ADJUST) is
      a multi-center international trial that will randomize 118 participants aged 2 years and
      older with controlled JIA-associated uveitis or chronic anterior uveitis to either continue
      adalimumab or discontinue adalimumab and receive a placebo. The trial will compare the time
      to uveitis recurrence between the two groups over 12 months. All participants will receive
      the standard weight-based dose of adalimumab or placebo: 20 mg biweekly (if < 30 kg) or 40 mg
      biweekly (if ≥ 30 kg).

      Impact: This is the first randomized controlled trial to assess the efficacy of discontinuing
      adalimumab after demonstrating control of JIA-associated uveitis for at least 12 months. The
      results of ADJUST will provide information on clinical outcomes to guide clinicians in their
      decision-making regarding discontinuation of adalimumab.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Time to treatment failure
time frame: From baseline until 12 months post-randomization
description: Time to treatment failure until 12 months post-randomization. Treatment failure is defined by recurrence of ocular inflammation in at least one eye as follows:
3+ anterior chamber (AC) for a single visit
•>0.5+ anterior chamber (AC) cell for ≥28 days
2-step increase in AC cell observed at two separate visits ≥7 days apart
0.5+ vitreous haze, active retinal or choroidal inflammation, or macular edema observed at a single visit. Treatment failure can also be declared by recurrence of joint inflammation that is persistent and severe enough to necessitate unmasking to manage the arthritis recurrence.
arm group label: Continue adalimumab
arm group type: Active Comparator
description: Patients randomized to this arm will continue adalimumab at their current dose (either 20mg/0.2mL or 40mg/0.4mL) administered subcutaneously every other week.
arm group label: Stop adalimumab
arm group type: Placebo Comparator
description: Patients randomized to this arm will receive a volume-matched placebo (0.8mL) administered subcutaneously every other week.
intervention type: Biological
intervention name: Adalimumab
description: Adalimumab is a fully human monoclonal anti-tumor necrosis factor alpha antibody, a biologic, immunomodulatory drug. Adalimumab 20mg/0.8mL and 40mg/0.8mL is a clear, colorless solution provided in a pre-filled syringe for subcutaneous injection. The formulation is adalimumab, mannitol, polysorbate 80, and water for injection Each pre-filled syringe has a fixed 29-gauge thin wall and ½ inch needle with black protective cover and is intended for a single dose to a single patient.
arm group label: Continue adalimumab
other name: HUMIRA
intervention type: Other
intervention name: Placebo
description: The placebo solution is a clear, colorless solution provided in a single-use, pre-filled syringe for subcutaneous injection. The placebo is designed to match the characteristics of the citrate-free adalimumab during injection.
arm group label: Stop adalimumab
criteria: 
gender: All
minimum age: 2 Years
maximum age: N/A
healthy volunteers: No
last name: Nisha Acharya, MD MS
role: Principal Investigator
affiliation: Principal Investigator
last name: Nisha Acharya, MD MS
phone: 415-476-8131
email: nisha.acharya@ucsf.edu
facility: 
status: Recruiting
contact: 
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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country: Australia
country: United Kingdom
country: United States
citation: Jaffe GJ, Dick AD, Brezin AP, Nguyen QD, Thorne JE, Kestelyn P, Barisani-Asenbauer T, Franco P, Heiligenhaus A, Scales D, Chu DS, Camez A, Kwatra NV, Song AP, Kron M, Tari S, Suhler EB. Adalimumab in Patients with Active Noninfectious Uveitis. N Engl J Med. 2016 Sep 8;375(10):932-43. doi: 10.1056/NEJMoa1509852.
PMID: 27602665
citation: Nguyen QD, Merrill PT, Jaffe GJ, Dick AD, Kurup SK, Sheppard J, Schlaen A, Pavesio C, Cimino L, Van Calster J, Camez AA, Kwatra NV, Song AP, Kron M, Tari S, Brezin AP. Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet. 2016 Sep 17;388(10050):1183-92. doi: 10.1016/S0140-6736(16)31339-3. Epub 2016 Aug 16. Erratum In: Lancet. 2016 Sep 17;388(10050):1160.
PMID: 27542302
citation: Ramanan AV, Dick AD, Benton D, Compeyrot-Lacassagne S, Dawoud D, Hardwick B, Hickey H, Hughes D, Jones A, Woo P, Edelsten C, Beresford MW; SYCAMORE Trial Management Group. A randomised controlled trial of the clinical effectiveness, safety and cost-effectiveness of adalimumab in combination with methotrexate for the treatment of juvenile idiopathic arthritis associated uveitis (SYCAMORE Trial). Trials. 2014 Jan 9;15:14. doi: 10.1186/1745-6215-15-14.
PMID: 24405833
citation: Vazquez-Cobian LB, Flynn T, Lehman TJ. Adalimumab therapy for childhood uveitis. J Pediatr. 2006 Oct;149(4):572-5. doi: 10.1016/j.jpeds.2006.04.058.
PMID: 17011337
citation: Chang CY, Meyer RM, Reiff AO. Impact of medication withdrawal method on flare-free survival in patients with juvenile idiopathic arthritis on combination therapy. Arthritis Care Res (Hoboken). 2015 May;67(5):658-66. doi: 10.1002/acr.22477.
PMID: 25220674
citation: Baszis K, Garbutt J, Toib D, Mao J, King A, White A, French A. Clinical outcomes after withdrawal of anti-tumor necrosis factor alpha therapy in patients with juvenile idiopathic arthritis: a twelve-year experience. Arthritis Rheum. 2011 Oct;63(10):3163-8. doi: 10.1002/art.30502.
PMID: 21702011
citation: Shakoor A, Esterberg E, Acharya NR. Recurrence of uveitis after discontinuation of infliximab. Ocul Immunol Inflamm. 2014 Apr;22(2):96-101. doi: 10.3109/09273948.2013.812222. Epub 2013 Jul 22.
PMID: 23876234
citation: Acharya NR, Ebert CD, Kelly NK, Porco TC, Ramanan AV, Arnold BF; ADJUST Research Group. Discontinuing adalimumab in patients with controlled juvenile idiopathic arthritis-associated uveitis (ADJUST-Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial): study protocol for a randomised controlled trial. Trials. 2020 Oct 27;21(1):887. doi: 10.1186/s13063-020-04796-z.
PMID: 33109240
responsible party type: Sponsor-Investigator
investigator affiliation: University of California, San Francisco
investigator full name: Nisha Acharya
investigator title: Director, Uveitis and Ocular Inflammatory Disease Service
mesh term: Uveitis
mesh term: Adalimumab
sharing ipd: No