<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/NCT01717170</url>
  </required_header>
  <id_info>
    <org_study_id>ML28522</org_study_id>
    <nct_id>NCT01717170</nct_id>
  </id_info>
  <brief_title>Study of the Safety, Tolerability, and Bioactivity of Tocilizumab On Patients With Non-infectious UVEITIS: The STOP-UVEITIS Study</brief_title>
  <acronym>STOP-Uveitis</acronym>
  <official_title>Study of the Safety, Tolerability, and Bioactivity of Tocilizumab On Patients With Non-infectious UVEITIS: The STOP-UVEITIS Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nebraska</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Nebraska</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In the STOP-UVEITIS study, we propose to evaluate the safety, tolerability, and bioactivity&#xD;
      of two doses of Tocilizumab (4mg/kg and 8mg/kg), administered monthly, in patients with&#xD;
      non-infectious intermediate, posterior, or panuveitis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>March 2013</start_date>
  <completion_date type="Anticipated">December 2017</completion_date>
  <primary_completion_date type="Anticipated">June 2017</primary_completion_date>
  <phase>Phase 1/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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency and severity of adverse events from baseline (BL) to month 6.</measure>
    <time_frame>Baseline (BL) to month 6.</time_frame>
    <description>Safety and tolerability of repeated Tocilizumab infusions in patients with non-infectious uveitis, as assessed by frequency and severity of adverse events from baseline (BL) to month 6.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency and severity of adverse events at month 12.</measure>
    <time_frame>Baseline to Month 12</time_frame>
    <description>Safety and tolerability of repeated Tocilizumab infusions in patients with non-infectious uveitis, as assessed by frequency and severity of adverse events at month 12.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Percentage of patients with a decrease of ≥ 2 steps in vitreous haze or resolution of haze (for patients with 1+ haze at baseline) based on the National Eye Institute (NEI) scale at 1, 3, 6, and 12 months after therapy or at time of rescue.</measure>
    <time_frame>Months 1, 3, 6, and 12 after therapy or at the time of rescue therapy administration.</time_frame>
    <description>Percentage of patients with a decrease of ≥ 2 steps in vitreous haze or resolution of haze (for patients with 1+ haze at baseline) based on the National Eye Institute (NEI) scale at 1, 3, 6, and 12 months after therapy or at time of rescue. All patients who receive rescue therapy will be followed until the conclusion of month 12.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">36</enrollment>
  <condition>Intermediate Uveitis</condition>
  <condition>Posterior Uveitis</condition>
  <condition>Pan-uveitis</condition>
  <arm_group>
    <arm_group_label>Tocilizumab (4 mg/kg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tocilizumab (4 mg/kg) as an intravenous infusion over 1 hour at day 0, 30, 60, 90, 120, and 150.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tocilizumab (8 mg/kg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tocilizumab (8 mg/kg) as an intravenous infusion over 1 hour at day 0, 30, 60, 90, 120, and 150.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tocilizumab</intervention_name>
    <description>Tocilizumab (4 mg/kg or 8 mg/kg)</description>
    <arm_group_label>Tocilizumab (4 mg/kg)</arm_group_label>
    <arm_group_label>Tocilizumab (8 mg/kg)</arm_group_label>
    <other_name>ACTEMRA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18;&#xD;
&#xD;
          -  Able to give informed consent and attend all study visits;&#xD;
&#xD;
          -  Have diagnosis of uveitis determined by the Investigator to be non-infectious;&#xD;
&#xD;
          -  Have active uveitis, defined as having at least 1+ Vitreous Haze (SUN scale) in study&#xD;
             eye. As mentioned above, at least 12 of the randomized subjects must also have&#xD;
             vitreous haze of ≥ 2+ vitreous haze. and:&#xD;
&#xD;
          -  are receiving no other treatment; or,&#xD;
&#xD;
          -  are receiving prednisone ≥10 mg/day (or equivalent dose of another corticosteroid)&#xD;
             and/or at least 1 other systemic immunosuppressant;&#xD;
&#xD;
          -  Have posterior, intermediate, or panuveitis; for panuveitis, if an anterior component&#xD;
             is present, it must be less than the posterior component;&#xD;
&#xD;
          -  Sufficient inflammation to require systemic treatment or long-term regional treatment.&#xD;
             Patients whom the investigators feel may only need short-term topical therapy should&#xD;
             not be enrolled.&#xD;
&#xD;
          -  Best-corrected EARLY TREATMENT DIABETIC RETINOPATHY STUDY(ETDRS) visual acuity of&#xD;
             20/20 to 20/400 (approximately 80 to 20 letters) in the study eye;&#xD;
&#xD;
          -  Best- corrected ETDRS visual acuity of 20/400 or better in the fellow eye&#xD;
             (approximately 20 letters).&#xD;
&#xD;
          -  Must have a chest radiograph within 3 months prior to enrollment with no evidence of&#xD;
             malignancy, infection or fibrosis.&#xD;
&#xD;
          -  Females of childbearing potential must have a negative serum pregnancy test at&#xD;
             screening. In addition, sexually active females of childbearing potential must agree&#xD;
             to use TWO of the following adequate forms of contraception while on study medication:&#xD;
             oral, injectable, or implantable hormonal contraceptives; tubal ligation; intrauterine&#xD;
             device; barrier contraceptive with spermicide; or vasectomized partner.&#xD;
&#xD;
          -  Males must agree to use barrier contraception (latex condoms) when engaging in sexual&#xD;
             activity while on study medication and for 28 days after taking the last dose of study&#xD;
             medication.&#xD;
&#xD;
          -  Subjects with a documented history of non-infectious intermediate-, anterior and&#xD;
             intermediate, posterior, or pan-uveitis including but not restricted to: intermediate&#xD;
             uveitis, sarcoidosis, Vogt-Koyanagi-Harada (VKH) syndrome, birdshot&#xD;
             retinochoroidopathy, retinal vasculitis, sympathetic ophthalmia, multifocal&#xD;
             choroiditis with panuveitis. Prior to study screening, potential subjects must have&#xD;
             been evaluated and screened for infectious etiologies by the investigators, possibly&#xD;
             as part of standard clinical acre; all testing to rule out infectious causes must be&#xD;
             performed within 3 months of screening for the STOP-UVEITIS study.&#xD;
&#xD;
          -  Currently active and uncontrolled uveitis (of the types mentioned above) that at the&#xD;
             determination of the investigator, requires the initiation of corticosteroid&#xD;
             monotherapy at a dose of ≥ 10 mg/day (or equivalent) or prednisone therapy and&#xD;
             immunomodulatory therapy or injections of corticosteroid (intravitreal or periocular);&#xD;
             or uveitis in subjects for whom oral corticosteroid is contraindicated, relatively or&#xD;
             absolutely.&#xD;
&#xD;
          -  Evidence of active non-infectious ocular inflammation, that at the determination of&#xD;
             investigator, requires therapy (e.g. vitreous cells, vitreous haze, retinal&#xD;
             vasculitis, chorioretinitis). Such evidence can be documented by clinical examination,&#xD;
             photography, or ancillary testing (e.g. fluorescein angiography, indocyanine green&#xD;
             (ICG), optical coherence tomography). As long as the investigator determines that the&#xD;
             degree of inflammation can be monitored for regression or progression, the&#xD;
             inflammation criterion can be met.&#xD;
&#xD;
          -  Not planning to undergo elective ocular surgery during the first 6 months of the&#xD;
             study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any significant ocular disease that could compromise vision in the study eye. These&#xD;
             include, but are not limited to:&#xD;
&#xD;
               -  Diabetic retinopathy: proliferative diabetic retinopathy (PDR) or&#xD;
                  non-proliferative diabetic retinopathy (NPDR) that compromise the vision.&#xD;
&#xD;
               -  Age-related macular degeneration;&#xD;
&#xD;
               -  Myopic degeneration with active subfoveal choroidal neovascularization.&#xD;
&#xD;
               -  Advanced glaucoma status post trabeculectomy or tube/valve placement&#xD;
&#xD;
          -  Any of the following treatments within 90 days prior to Day 0 or anticipated use of&#xD;
             any of the following treatments to the study eye:&#xD;
&#xD;
               -  Intravitreal injections (including but not limited to steroids or anti-vascular&#xD;
                  endothelial growth factors);&#xD;
&#xD;
               -  Posterior subtenon's steroids&#xD;
&#xD;
          -  Intraocular surgery within 90 days prior to Day 0 in the study eye;&#xD;
&#xD;
          -  Capsulotomy within 30 days prior to Day 0 in the study eye;&#xD;
&#xD;
          -  History of vitreoretinal surgery or scleral buckling&#xD;
&#xD;
          -  Any ocular surgery (including cataract extraction or capsulotomy) of the study eye&#xD;
             anticipated within the first 180 days following Day 0;&#xD;
&#xD;
          -  Intraocular pressure (IOP) ≥25 mmHg in the study eye (glaucoma patients maintained on&#xD;
             no more than 2 topical medications with IOP &lt;25 mmHg are allowed to participate);&#xD;
&#xD;
          -  Pupillary dilation inadequate for quality stereoscopic fundus photography in the study&#xD;
             eye;&#xD;
&#xD;
          -  Media opacity that would limit clinical visualization;&#xD;
&#xD;
          -  Presence of any form of ocular malignancy in the study eye, including choroidal&#xD;
             melanoma;&#xD;
&#xD;
          -  History of herpetic infection in the study eye or adnexa;&#xD;
&#xD;
          -  Presence of known active or inactive toxoplasmosis in either eye;&#xD;
&#xD;
          -  Ocular or periocular infection in either eye;&#xD;
&#xD;
          -  Participation in other investigational drug or device clinical trials within 30 days&#xD;
             prior to Day 0, or planning to participate in other investigational drug or device&#xD;
             clinical trials within 180 days following Day 0. This includes both ocular and&#xD;
             non-ocular clinical trials&#xD;
&#xD;
          -  Major surgery (including joint surgery) within 8 weeks prior to screening or planned&#xD;
             major surgery within 6 months following randomization&#xD;
&#xD;
          -  Prior treatment with any cell-depleting therapies, including investigational agents or&#xD;
             approved therapies, some examples are CAMPATH, anti-CD4, anti-CD5, anti¬CD3, anti-CD19&#xD;
             and anti-CD20&#xD;
&#xD;
          -  Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6&#xD;
             months of baseline&#xD;
&#xD;
          -  Immunization with a live/attenuated vaccine within 4 weeks prior to baseline&#xD;
&#xD;
          -  Previous treatment with tocilizumab (TCZ)&#xD;
&#xD;
          -  Any previous treatment with alkylating agents such as chlorambucil, or with total&#xD;
             lymphoid irradiation&#xD;
&#xD;
          -  History of severe allergic or anaphylactic reactions to human, humanized or murine&#xD;
             monoclonal antibodies&#xD;
&#xD;
          -  Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary&#xD;
             (including obstructive pulmonary disease), renal, hepatic, endocrine (include&#xD;
             uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated&#xD;
             diverticulitis, ulcerative colitis, or Crohn&quot;s disease)&#xD;
&#xD;
          -  Current liver disease as determined by principal investigator unless related to&#xD;
             primary disease under investigation&#xD;
&#xD;
          -  Known active current or history of recurrent bacterial, viral, fungal, mycobacterial&#xD;
             or other infections (including but not limited to tuberculosis and atypical&#xD;
             mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding fungal&#xD;
             infections of nail beds)&#xD;
&#xD;
          -  Any major episode of infection requiring hospitalization or treatment with IV&#xD;
             antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to&#xD;
             screening&#xD;
&#xD;
          -  Active tuberculosis (TB) requiring treatment within the previous 3 years. Patients&#xD;
             should be screened for latent TB and, if positive, treated following local practice&#xD;
             guidelines prior to initiating (Tocilizumab)TCZ. Patients treated for tuberculosis&#xD;
             with no recurrence in 3 years are permitted&#xD;
&#xD;
          -  Primary or secondary immunodeficiency (history of or currently active)&#xD;
&#xD;
          -  Evidence of active malignant disease, malignancies diagnosed within the previous 5&#xD;
             years (including hematological malignancies and solid tumors, except basal and&#xD;
             squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has&#xD;
             been excised and cured)&#xD;
&#xD;
          -  Pregnant women or nursing (breast feeding) mothers&#xD;
&#xD;
          -  Patients with reproductive potential not willing to use an effective method of&#xD;
             contraception&#xD;
&#xD;
          -  History of alcohol, drug or chemical abuse within 1 year prior to screening.&#xD;
&#xD;
          -  Neuropathies or other conditions that might interfere with pain evaluation unless&#xD;
             related to primary disease under investigation&#xD;
&#xD;
          -  Patients with lack of peripheral venous access&#xD;
&#xD;
          -  Serum creatinine &gt; 1.6 mg/dL (141 μmol/L) in female patients and &gt; 1.9 mg/dL(168&#xD;
             μmol/L) in male patients. Patients with serum creatinine values exceeding limits may&#xD;
             be eligible for the study if their estimated glomerular filtration rates (GFR) are&#xD;
             &gt;30.&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) &gt; 1.5 times upper&#xD;
             limit of normal (ULN)&#xD;
&#xD;
          -  Total Bilirubin &gt; ULN&#xD;
&#xD;
          -  Platelet count &lt; 100 x 109/L (100,000/mm3)&#xD;
&#xD;
          -  Hemoglobin &lt; 85 g/L (8.5 g/dL; 5.3 mmol/L)&#xD;
&#xD;
          -  White Blood Cells &lt; 3.0 x 109/L (3000/mm3)&#xD;
&#xD;
          -  Absolute Neutrophil Count &lt; 2.0 x 109/L (2000/mm3)&#xD;
&#xD;
          -  Absolute Lymphocyte Count &lt; 0.5 x 109/L (500/mm3)&#xD;
&#xD;
          -  Positive Hepatitis BsAg, or Hepatitis C antibody&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Quan D Nguyen, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Truhlsen Eye Institute, University of Nebraska Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Truhlsen Eye Institute, University Of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>October 26, 2012</study_first_submitted>
  <study_first_submitted_qc>October 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 30, 2012</study_first_posted>
  <last_update_submitted>April 26, 2017</last_update_submitted>
  <last_update_submitted_qc>April 26, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Nebraska</investigator_affiliation>
    <investigator_full_name>Quan Dong Nguyen, MD</investigator_full_name>
    <investigator_title>Professor and Chair</investigator_title>
  </responsible_party>
  <keyword>Non-infectious Uveitis, Tocilizumab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uveitis</mesh_term>
    <mesh_term>Uveitis, Posterior</mesh_term>
    <mesh_term>Uveitis, Intermediate</mesh_term>
    <mesh_term>Pars Planitis</mesh_term>
    <mesh_term>Panuveitis</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01717170
org study id: ML28522
nct id: NCT01717170
lead sponsor: 
has dmc: No
In the STOP-UVEITIS study, we propose to evaluate the safety, tolerability, and bioactivity
      of two doses of Tocilizumab (4mg/kg and 8mg/kg), administered monthly, in patients with
      non-infectious intermediate, posterior, or panuveitis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Frequency and severity of adverse events from baseline (BL) to month 6.
time frame: Baseline (BL) to month 6.
description: Safety and tolerability of repeated Tocilizumab infusions in patients with non-infectious uveitis, as assessed by frequency and severity of adverse events from baseline (BL) to month 6.
measure: Frequency and severity of adverse events at month 12.
time frame: Baseline to Month 12
description: Safety and tolerability of repeated Tocilizumab infusions in patients with non-infectious uveitis, as assessed by frequency and severity of adverse events at month 12.
measure: Percentage of patients with a decrease of ≥ 2 steps in vitreous haze or resolution of haze (for patients with 1+ haze at baseline) based on the National Eye Institute (NEI) scale at 1, 3, 6, and 12 months after therapy or at time of rescue.
time frame: Months 1, 3, 6, and 12 after therapy or at the time of rescue therapy administration.
description: Percentage of patients with a decrease of ≥ 2 steps in vitreous haze or resolution of haze (for patients with 1+ haze at baseline) based on the National Eye Institute (NEI) scale at 1, 3, 6, and 12 months after therapy or at time of rescue. All patients who receive rescue therapy will be followed until the conclusion of month 12.
arm group label: Tocilizumab (4 mg/kg)
arm group type: Experimental
description: Tocilizumab (4 mg/kg) as an intravenous infusion over 1 hour at day 0, 30, 60, 90, 120, and 150.
arm group label: Tocilizumab (8 mg/kg)
arm group type: Experimental
description: Tocilizumab (8 mg/kg) as an intravenous infusion over 1 hour at day 0, 30, 60, 90, 120, and 150.
intervention type: Drug
intervention name: Tocilizumab
description: Tocilizumab (4 mg/kg or 8 mg/kg)
arm group label: Tocilizumab (4 mg/kg)
arm group label: Tocilizumab (8 mg/kg)
other name: ACTEMRA
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Quan D Nguyen, MD, MSc
role: Principal Investigator
affiliation: Truhlsen Eye Institute, University of Nebraska Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Nebraska
investigator full name: Quan Dong Nguyen, MD
investigator title: Professor and Chair
mesh term: Uveitis
mesh term: Uveitis, Posterior
mesh term: Uveitis, Intermediate
mesh term: Pars Planitis
mesh term: Panuveitis