<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/NCT03298867</url>
  </required_header>
  <id_info>
    <org_study_id>HZNP-TEP-301</org_study_id>
    <secondary_id>2017-002763-18</secondary_id>
    <nct_id>NCT03298867</nct_id>
  </id_info>
  <brief_title>Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis With Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study</brief_title>
  <acronym>OPTIC</acronym>
  <official_title>A Phase 3, Randomized, Double-Masked, Placebo-Controlled, Parallel-Group, Multicenter Study Evaluating Teprotumumab (HZN-001) Treatment in Subjects With Active Thyroid Eye Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Horizon Pharma USA, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Horizon Pharma USA, Inc.</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 overall objective is to investigate the efficacy, tolerability, and safety of&#xD;
      teprotumumab (a fully human monoclonal antibody [mAb] inhibitor of the insulin-like growth&#xD;
      factor-1 receptor [IGF-1R]) administered once every 3 weeks (q3W) for 21 weeks with a final&#xD;
      assessment at Week 24, in comparison to placebo, in the treatment of participants with&#xD;
      moderate-to-severe active thyroid eye disease (TED).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-masked, placebo-controlled, parallel-group, multicenter study.&#xD;
      Approximately 76 participants (38/group) who meet the study eligibility criteria will be&#xD;
      randomized on Day 1 in a 1:1 ratio (stratified by tobacco use status) to receive 8 infusions&#xD;
      of teprotumumab or placebo q3W. All participants will enter a 24-week double-masked Treatment&#xD;
      Period, during which study drug will be infused on Day 1 (Baseline), and Weeks 3, 6, 9, 12,&#xD;
      15, 18, and 21 (with a final visit at Week 24). All study drug dosing will be performed at&#xD;
      the clinic under the supervision of clinic staff. On each dosing day, scheduled assessments&#xD;
      (except for adverse event [AE] and concomitant medication use monitoring, which will be&#xD;
      monitored throughout the clinic visit) will be completed prior to study drug dosing.&#xD;
&#xD;
      At the end of the double-masked Treatment Period (Week 24), participants who are proptosis&#xD;
      non-responders (study eye has &lt; 2 mm decrease in proptosis) will be eligible to enter an&#xD;
      open-label extension study in which participants receive 8 infusions of teprotumumab in an&#xD;
      open-label fashion.&#xD;
&#xD;
      At Week 24, proptosis responders, as well as non-responders who choose not to enroll in the&#xD;
      open-label extension study, will enter a 48-week Follow-Up Period, during which study drug&#xD;
      will not be administered and clinic visits are scheduled for Weeks 28, 36, 48, 60, and 72.&#xD;
      Participants who are considered responders at Week 24 but who meet criteria for re-treatment&#xD;
      due to relapse during the Follow-Up Period may enroll in the open-label extension study.&#xD;
&#xD;
      Participants who complete the Week 72 Visit will be contacted 6 and 12 months later via phone&#xD;
      or email by research staff to enquire if any treatment for TED has been received since last&#xD;
      study contact.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 4, 2017</start_date>
  <completion_date type="Actual">November 30, 2020</completion_date>
  <primary_completion_date type="Actual">February 13, 2019</primary_completion_date>
  <phase>Phase 3</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>Percentage of Participants Who Were Proptosis Responders at Week 24</measure>
    <time_frame>Week 24</time_frame>
    <description>Proptosis responders were defined as participants with a ≥2 mm reduction from Baseline in proptosis in the study eye, without deterioration (≥2 mm increase) of proptosis in the fellow eye at Week 24.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Were Overall Responders at Week 24</measure>
    <time_frame>Week 24</time_frame>
    <description>Overall responders were defined as participants with a ≥2 mm reduction in proptosis AND a ≥2 point reduction in Clinical Activity Score (CAS) from Baseline in the study eye, without deterioration (≥2 mm increase in proptosis or ≥2 point increase in CAS) in the fellow eye at Week 24.&#xD;
The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/ Graves' Ophthalmopathy or Orbitopathy (TED/GO); 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (ignore &quot;equivocal&quot; redness); 6. Chemosis; 7. Inflammation of caruncle or plica. Each item is scored (1=present; 0=absent) and scores for each item are summed for total score of 0 (no clinical activity) to 7 (most clinical activity).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Were CAS Categorical Responders at Week 24 (Study Eye)</measure>
    <time_frame>Week 24</time_frame>
    <description>CAS categorical responders were defined as participants with a reduction to a CAS of 0 or 1 (no or minimal inflammatory symptoms) in study eye.&#xD;
The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/ Graves' Ophthalmopathy or Orbitopathy (TED/GO); 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (ignore &quot;equivocal&quot; redness); 6. Chemosis; 7. Inflammation of caruncle or plica. Each item is scored (1=present; 0=absent) and scores for each item are summed for total score of 0 (no inflammatory symptoms) to 7 (most inflammatory symptoms).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Proptosis to Week 24 (Study Eye)</measure>
    <time_frame>Baseline, up to Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Were Diplopia Responders at Week 24</measure>
    <time_frame>Week 24</time_frame>
    <description>Diplopia responders were defined as participants with Baseline diplopia Subjective Diplopia Score grade &gt;0 in the study eye who had a reduction of ≥1 grade with no corresponding deterioration (≥1 grade worsening) in the fellow eye at Week 24. Denominator is the number of subjects with diplopia at Baseline.&#xD;
The Subjective Diplopia Score is a clinical measure of diplopia severity on a grade scale of 0 to 3: 0=no diplopia; 1=intermittent (diplopia in primary position of gaze, when tired or when first awakening); 2=inconstant (diplopia at extremes of gaze); 3=constant (continuous diplopia in primary or reading position).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score to Week 24</measure>
    <time_frame>Baseline, up to Week 24</time_frame>
    <description>The GO-QoL is a 16-item self-administered questionnaire divided into 2 subsets and used to assess the perceived effects of TED by the subjects on (i) their daily physical activity as it relates to visual function, and (ii) psychosocial functioning. The range of the GO-QoL overall transformed scores is 0 to 100, where higher values correspond to better quality of life.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">83</enrollment>
  <condition>Thyroid Eye Disease</condition>
  <condition>Graves' Orbitopathy</condition>
  <arm_group>
    <arm_group_label>Teprotumumab 20 mg/kg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Approximately 38 participants will receive 8 infusions of teprotumumab q3W for a total of 21 weeks. Teprotumumab 10 mg/kg will be administered on Day 1 and teprotumumab 20 mg/kg will be administered q3W for the remaining 7 infusions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Approximately 38 participants will receive 8 infusions of placebo q3W for a total of 21 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Teprotumumab</intervention_name>
    <description>Teprotumumab is a fully human anti-IGF-1R mAb. Teprotumumab will be provided in single-dose 20 mL glass vials as a freeze-dried powder. Each vial of teprotumumab must be reconstituted with 10 mL of water for injection. Reconstituted teprotumumab solution must be further diluted in 0.9% (w/v) sodium chloride (NaCl) solution prior to administration. Teprotumumab will be administered in 100 mL or 250 mL infusion bags (100 mL infusion bags for doses up to 1800 mg and 250 mL infusion bags for doses &gt; 1800 mg).</description>
    <arm_group_label>Teprotumumab 20 mg/kg</arm_group_label>
    <other_name>HZN-001</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo will consist of normal saline (0.9% NaCl) solution and will be administered in 100 mL or 250 mL infusion bags, as would be appropriate, per weight-based dosing volumes (100 mL infusion bags for doses up to 1800 mg and 250 mL infusion bags for doses &gt; 1800 mg).</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Saline solution</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent.&#xD;
&#xD;
          2. Male or female participant between the ages of 18 and 80 years, inclusive, at&#xD;
             Screening.&#xD;
&#xD;
          3. Clinical diagnosis of Graves' disease associated with active TED with a Clinical&#xD;
             Activity Score (CAS) ≥ 4 (on the 7-item scale) for the most severely affected eye at&#xD;
             Screening and Baseline.&#xD;
&#xD;
          4. Moderate-to-severe active TED (not sight-threatening but has an appreciable impact on&#xD;
             daily life), usually associated with one or more of the following: lid retraction ≥ 2&#xD;
             mm, moderate or severe soft tissue involvement, exophthalmos ≥ 3 mm above normal for&#xD;
             race and gender, and/or inconstant or constant diplopia.&#xD;
&#xD;
          5. Onset of active TED symptoms (as determined by participant records) within 9 months&#xD;
             prior to Baseline.&#xD;
&#xD;
          6. Participants must be euthyroid with the baseline disease under control or have mild&#xD;
             hypo- or hyperthyroidism (defined as free thyroxine [FT4] and free triiodothyronine&#xD;
             [FT3] levels &lt; 50% above or below the normal limits) at Screening. Every effort should&#xD;
             be made to correct the mild hypo- or hyperthyroidism promptly and to maintain the&#xD;
             euthyroid state for the full duration of the clinical trial.&#xD;
&#xD;
          7. Does not require immediate surgical ophthalmological intervention and is not planning&#xD;
             corrective surgery/irradiation during the course of the study.&#xD;
&#xD;
          8. Alanine aminotransferase (ALT) or AST ≤ 3 times the upper limit of normal (ULN) or&#xD;
             serum creatine &lt;1.5 times the ULN according to age at Screening.&#xD;
&#xD;
          9. Diabetic participants must have well-controlled stable disease (defined as HbA1C &lt;&#xD;
             9.0% with no new diabetic medication [oral or insulin] or more than a 10% change in&#xD;
             the dose of a currently prescribed diabetic medication within 60 days prior to&#xD;
             Screening).&#xD;
&#xD;
         10. Women of childbearing potential (including those with an onset of menopause &lt;2 years&#xD;
             prior to Screening, non-therapy-induced amenorrhea for &lt;12 months prior to Screening,&#xD;
             or not surgically sterile [absence of ovaries and/or uterus]) must have a negative&#xD;
             serum pregnancy test at Screening and negative urine pregnancy tests at all&#xD;
             protocol-specified timepoints (i.e., prior to each dose and through Week 48 of the&#xD;
             Follow-Up Period); participants who are sexually active with a non-vasectomized male&#xD;
             partner must agree to use 2 reliable forms of contraception during the trial, one of&#xD;
             which is recommended to be hormonal, such as an oral contraceptive. Hormonal&#xD;
             contraception must be started at least one full cycle prior to Baseline and continue&#xD;
             for 180 days after the last dose of study drug. Highly effective contraceptive methods&#xD;
             (with a failure rate less than 1% per year) when used consistently and correctly,&#xD;
             includes implants, injectables, combined oral contraceptives, intrauterine devices&#xD;
             (IUDs), sexual abstinence or vasectomized partner.&#xD;
&#xD;
         11. Male participants must be surgically sterile or, if sexually active with a female&#xD;
             partner of childbearing potential, must agree to use barrier contraceptive method from&#xD;
             Screening through 180 days after the last dose of study drug.&#xD;
&#xD;
         12. Participant is willing and able to comply with the study protocol and evaluations for&#xD;
             the duration of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Decreased best corrected visual acuity due to optic neuropathy as defined by a&#xD;
             decrease in vision of 2 lines on the Snellen chart, new visual field defect, or color&#xD;
             defect secondary to optic nerve involvement within the last 6 months.&#xD;
&#xD;
          2. Corneal decompensation unresponsive to medical management.&#xD;
&#xD;
          3. Decrease in CAS of ≥ 2 points in the study eye between Screening and Baseline.&#xD;
&#xD;
          4. Decrease in proptosis of ≥ 2 mm in the study eye between Screening and Baseline.&#xD;
&#xD;
          5. Previous orbital irradiation or surgery for TED.&#xD;
&#xD;
          6. Any steroid use (intravenous [IV] or oral) with a cumulative dose equivalent to ≥ 1 g&#xD;
             of methylprednisolone for the treatment of TED. Previous steroid use (IV or oral) with&#xD;
             a cumulative dose of &lt;1 g methylprednisolone or equivalent for the treatment of TED&#xD;
             and previous use of steroid eye drops is allowed if the corticosteroid was&#xD;
             discontinued at least 4 weeks prior to Screening.&#xD;
&#xD;
          7. Corticosteroid use for conditions other than TED within 4 weeks prior to Screening&#xD;
             (topical steroids for dermatological conditions and inhaled steroids are allowed).&#xD;
&#xD;
          8. Selenium and biotin must be discontinued 3 weeks prior to Screening and must not be&#xD;
             restarted during the clinical trial; however, taking a multivitamin that includes&#xD;
             selenium and/or biotin is allowed.&#xD;
&#xD;
          9. Any previous treatment with rituximab or tocilizumab. Use of any other non-steroid&#xD;
             immunosuppressive agent within 3 months prior to Screening.&#xD;
&#xD;
         10. Use of an investigational agent for any condition within 60 days prior to Screening or&#xD;
             anticipated use during the course of the trial.&#xD;
&#xD;
         11. Identified pre-existing ophthalmic disease that, in the judgment of the Investigator,&#xD;
             would preclude study participation or complicate interpretation of study results.&#xD;
&#xD;
         12. Bleeding diathesis that in the judgment of the Investigator would preclude inclusion&#xD;
             in the clinical trial.&#xD;
&#xD;
         13. Malignant condition in the past 12 months (except successfully treated basal/squamous&#xD;
             cell carcinoma of the skin).&#xD;
&#xD;
         14. Pregnant or lactating women.&#xD;
&#xD;
         15. Current drug or alcohol abuse, or history of either within the previous 2 years, in&#xD;
             the opinion of the Investigator or as reported by the participant.&#xD;
&#xD;
         16. Biopsy-proven or clinically suspected inflammatory bowel disease.&#xD;
&#xD;
         17. Known hypersensitivity to any of the components of teprotumumab or prior&#xD;
             hypersensitivity reactions to mAbs.&#xD;
&#xD;
         18. Any other condition that, in the opinion of the Investigator, would preclude inclusion&#xD;
             in the study.&#xD;
&#xD;
         19. Previous enrollment in this study or participation in a prior teprotumumab clinical&#xD;
             trial.&#xD;
&#xD;
         20. Human immunodeficiency virus (HIV), hepatitis C or hepatitis B infections.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Raymond Douglas, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cedars-Sinai Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>George Kahaly, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johannes Gutenberg University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Macro, Llc</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedars-Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90078</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Lennar Foundation Medical</name>
      <address>
        <city>Coral Gables</city>
        <state>Florida</state>
        <zip>33146</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bascom Palmer Eye Institute</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kellogg Eye Center at University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Casey Eye Institute at Oregon Health and Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hamilton Eye Institute at University of Tennessee Health Science Center</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38163</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eye Wellness Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77005</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin, The Eye Institute</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Essen, Department of Ophthalmology</name>
      <address>
        <city>Essen</city>
        <zip>45147</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johannes Gutenberg University Medical Center</name>
      <address>
        <city>Mainz</city>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico</name>
      <address>
        <city>Milan</city>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pisa, Department of Clinical and Experimental Medicine</name>
      <address>
        <city>Pisa</city>
        <zip>56100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pisa,Department of Clinical and Experimental Medicine, Endocrinology Unit</name>
      <address>
        <city>Pisa</city>
        <zip>56124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Italy</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.tepezza.com/</url>
    <description>Related Info</description>
  </link>
  <results_reference>
    <citation>Douglas RS, Kahaly GJ, Patel A, Sile S, Thompson EHZ, Perdok R, Fleming JC, Fowler BT, Marcocci C, Marino M, Antonelli A, Dailey R, Harris GJ, Eckstein A, Schiffman J, Tang R, Nelson C, Salvi M, Wester S, Sherman JW, Vescio T, Holt RJ, Smith TJ. Teprotumumab for the Treatment of Active Thyroid Eye Disease. N Engl J Med. 2020 Jan 23;382(4):341-352. doi: 10.1056/NEJMoa1910434.</citation>
    <PMID>31971679</PMID>
  </results_reference>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>September 27, 2017</study_first_submitted>
  <study_first_submitted_qc>September 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 2, 2017</study_first_posted>
  <results_first_submitted>February 14, 2020</results_first_submitted>
  <results_first_submitted_qc>March 2, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 10, 2020</results_first_posted>
  <last_update_submitted>January 31, 2022</last_update_submitted>
  <last_update_submitted_qc>January 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Proptosis</keyword>
  <keyword>Human monoclonal antibody</keyword>
  <keyword>insulin-like growth factor-1 receptor</keyword>
  <keyword>Thyroid-Associated Ophthalmopathy</keyword>
  <keyword>Autoimmune Thyroid Disease</keyword>
  <keyword>Graves' Orbitopathy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Eye Diseases</mesh_term>
    <mesh_term>Graves Ophthalmopathy</mesh_term>
    <mesh_term>Thyroid Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 31, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/67/NCT03298867/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 8, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/67/NCT03298867/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Eight infusions of placebo every 3 weeks (q3W) for a total of 21 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Teprotumumab 20 mg/kg</title>
          <description>Eight infusions of teprotumumab every q3W for a total of 21 weeks. Teprotumumab 10 mg/kg administered on Day 1 and teprotumumab 20 mg/kg administered q3W for the remaining 7 infusions.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Double-Masked 24-Week Treatment Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="42"/>
                <participants group_id="P2" count="41"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="40">36 participants who completed the double-masked treatment period as nonresponders chose to enroll in the OPTIC-X open-label extension study (NCT03461211).</participants>
                <participants group_id="P2" count="39">3 participants who completed the double-masked treatment period as nonresponders chose to enroll in the OPTIC-X open-label extension study (NCT03461211).</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>48-Week Follow-Up Period (Weeks 24-72)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Relapsed/Entered OPTIC-X</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Relapsed/Did not enter OPTIC-X</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other, Not Specified</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Mis-classified as Responders</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>48-Week Follow-Up Contact (Weeks 96-120)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Eight infusions of placebo q3W for a total of 21 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Teprotumumab 20 mg/kg</title>
          <description>Eight infusions of teprotumumab q3W for a total of 21 weeks. Teprotumumab 10 mg/kg administered on Day 1 and teprotumumab 20 mg/kg administered q3W for the remaining 7 infusions.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="42"/>
            <count group_id="B2" value="41"/>
            <count group_id="B3" value="83"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="48.9" spread="12.96"/>
                    <measurement group_id="B2" value="51.6" spread="12.63"/>
                    <measurement group_id="B3" value="50.2" spread="12.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>&lt;65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>≥65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="60"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="80"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>More Than 1 Race</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Tobacco use status - as randomized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Non-User</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>User</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Tobacco use status - actual</title>
          <description>Actual tobacco use status reflects the status as reported on the substance use case report form. One participant was randomized in error to the tobacco user stratum as this subject was reported as a non-user (former tobacco use status) on the substance use case report form.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Non-User</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>User</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Who Were Proptosis Responders at Week 24</title>
        <description>Proptosis responders were defined as participants with a ≥2 mm reduction from Baseline in proptosis in the study eye, without deterioration (≥2 mm increase) of proptosis in the fellow eye at Week 24.</description>
        <time_frame>Week 24</time_frame>
        <population>Intent-to-treat population: all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Eight infusions of placebo q3W for a total of 21 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Teprotumumab 20 mg/kg</title>
            <description>Eight infusions of teprotumumab q3W for a total of 21 weeks. Teprotumumab 10 mg/kg administered on Day 1 and teprotumumab 20 mg/kg administered q3W for the remaining 7 infusions.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Were Proptosis Responders at Week 24</title>
          <description>Proptosis responders were defined as participants with a ≥2 mm reduction from Baseline in proptosis in the study eye, without deterioration (≥2 mm increase) of proptosis in the fellow eye at Week 24.</description>
          <population>Intent-to-treat population: all randomized participants.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.5"/>
                    <measurement group_id="O2" value="82.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>Two-sided p-value calculated assuming the test statistic was distributed as a standard normal random variable.</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Stratified difference in percentages</param_type>
            <param_value>73.45</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>7.43</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>58.89</ci_lower_limit>
            <ci_upper_limit>88.01</ci_upper_limit>
            <estimate_desc>Stratified difference (teprotumumab - placebo) is a weighted average of the difference within each stratum. Estimates from the 2 strata (tobacco user, tobacco non-user) were combined with Cochran-Mantel-Haenszel (CMH) weights.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Were Overall Responders at Week 24</title>
        <description>Overall responders were defined as participants with a ≥2 mm reduction in proptosis AND a ≥2 point reduction in Clinical Activity Score (CAS) from Baseline in the study eye, without deterioration (≥2 mm increase in proptosis or ≥2 point increase in CAS) in the fellow eye at Week 24.&#xD;
The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/ Graves' Ophthalmopathy or Orbitopathy (TED/GO); 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (ignore &quot;equivocal&quot; redness); 6. Chemosis; 7. Inflammation of caruncle or plica. Each item is scored (1=present; 0=absent) and scores for each item are summed for total score of 0 (no clinical activity) to 7 (most clinical activity).</description>
        <time_frame>Week 24</time_frame>
        <population>Intent-to-treat population: all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Eight infusions of placebo q3W for a total of 21 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Teprotumumab 20 mg/kg</title>
            <description>Eight infusions of teprotumumab q3W for a total of 21 weeks. Teprotumumab 10 mg/kg administered on Day 1 and teprotumumab 20 mg/kg administered q3W for the remaining 7 infusions.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Were Overall Responders at Week 24</title>
          <description>Overall responders were defined as participants with a ≥2 mm reduction in proptosis AND a ≥2 point reduction in Clinical Activity Score (CAS) from Baseline in the study eye, without deterioration (≥2 mm increase in proptosis or ≥2 point increase in CAS) in the fellow eye at Week 24.&#xD;
The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/ Graves' Ophthalmopathy or Orbitopathy (TED/GO); 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (ignore &quot;equivocal&quot; redness); 6. Chemosis; 7. Inflammation of caruncle or plica. Each item is scored (1=present; 0=absent) and scores for each item are summed for total score of 0 (no clinical activity) to 7 (most clinical activity).</description>
          <population>Intent-to-treat population: all randomized participants.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.1"/>
                    <measurement group_id="O2" value="78.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>Two-sided p-value calculated assuming the test statistic was distributed as a standard normal random variable.</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Stratified difference in percentages</param_type>
            <param_value>70.82</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>7.62</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>55.89</ci_lower_limit>
            <ci_upper_limit>85.75</ci_upper_limit>
            <estimate_desc>Stratified difference (teprotumumab - placebo) is a weighted average of the difference within each stratum. Estimates from the 2 strata (tobacco user, tobacco non-user) were combined with CMH weights.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Were CAS Categorical Responders at Week 24 (Study Eye)</title>
        <description>CAS categorical responders were defined as participants with a reduction to a CAS of 0 or 1 (no or minimal inflammatory symptoms) in study eye.&#xD;
The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/ Graves' Ophthalmopathy or Orbitopathy (TED/GO); 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (ignore &quot;equivocal&quot; redness); 6. Chemosis; 7. Inflammation of caruncle or plica. Each item is scored (1=present; 0=absent) and scores for each item are summed for total score of 0 (no inflammatory symptoms) to 7 (most inflammatory symptoms).</description>
        <time_frame>Week 24</time_frame>
        <population>Intent-to-treat population: all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Eight infusions of placebo q3W for a total of 21 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Teprotumumab 20 mg/kg</title>
            <description>Eight infusions of teprotumumab q3W for a total of 21 weeks. Teprotumumab 10 mg/kg administered on Day 1 and teprotumumab 20 mg/kg administered q3W for the remaining 7 infusions.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Were CAS Categorical Responders at Week 24 (Study Eye)</title>
          <description>CAS categorical responders were defined as participants with a reduction to a CAS of 0 or 1 (no or minimal inflammatory symptoms) in study eye.&#xD;
The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/ Graves' Ophthalmopathy or Orbitopathy (TED/GO); 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (ignore &quot;equivocal&quot; redness); 6. Chemosis; 7. Inflammation of caruncle or plica. Each item is scored (1=present; 0=absent) and scores for each item are summed for total score of 0 (no inflammatory symptoms) to 7 (most inflammatory symptoms).</description>
          <population>Intent-to-treat population: all randomized participants.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.4"/>
                    <measurement group_id="O2" value="58.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>Two-sided p-value calculated assuming the test statistic was distributed as a standard normal random variable.</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Stratified difference in percentages</param_type>
            <param_value>36.03</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>9.51</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>17.39</ci_lower_limit>
            <ci_upper_limit>54.67</ci_upper_limit>
            <estimate_desc>Stratified difference (teprotumumab - placebo) is a weighted average of the difference within each stratum. Estimates from the 2 strata (tobacco user, tobacco non-user) were combined with CMH weights.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Proptosis to Week 24 (Study Eye)</title>
        <time_frame>Baseline, up to Week 24</time_frame>
        <population>Intent-to-treat population: all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Eight infusions of placebo q3W for a total of 21 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Teprotumumab 20 mg/kg</title>
            <description>Eight infusions of teprotumumab q3W for a total of 21 weeks. Teprotumumab 10 mg/kg administered on Day 1 and teprotumumab 20 mg/kg administered q3W for the remaining 7 infusions.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Proptosis to Week 24 (Study Eye)</title>
          <population>Intent-to-treat population: all randomized participants.</population>
          <units>mm</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.54" spread="0.192"/>
                    <measurement group_id="O2" value="-2.82" spread="0.191"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>Results obtained from an MMRM with an unstructured covariance matrix including the following terms: Baseline value, tobacco use status, treatment group, visit, visit-by-treatment interaction and visit-by-Baseline-value interaction.</p_value_desc>
            <method>mixed model for repeated measures (MMRM)</method>
            <param_type>LS mean difference</param_type>
            <param_value>-2.28</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.244</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.77</ci_lower_limit>
            <ci_upper_limit>-1.80</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Were Diplopia Responders at Week 24</title>
        <description>Diplopia responders were defined as participants with Baseline diplopia Subjective Diplopia Score grade &gt;0 in the study eye who had a reduction of ≥1 grade with no corresponding deterioration (≥1 grade worsening) in the fellow eye at Week 24. Denominator is the number of subjects with diplopia at Baseline.&#xD;
The Subjective Diplopia Score is a clinical measure of diplopia severity on a grade scale of 0 to 3: 0=no diplopia; 1=intermittent (diplopia in primary position of gaze, when tired or when first awakening); 2=inconstant (diplopia at extremes of gaze); 3=constant (continuous diplopia in primary or reading position).</description>
        <time_frame>Week 24</time_frame>
        <population>Intent-to-treat population: all randomized participants with diplopia at baseline in the study eye.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Eight infusions of placebo q3W for a total of 21 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Teprotumumab 20 mg/kg</title>
            <description>Eight infusions of teprotumumab q3W for a total of 21 weeks. Teprotumumab 10 mg/kg administered on Day 1 and teprotumumab 20 mg/kg administered q3W for the remaining 7 infusions.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Were Diplopia Responders at Week 24</title>
          <description>Diplopia responders were defined as participants with Baseline diplopia Subjective Diplopia Score grade &gt;0 in the study eye who had a reduction of ≥1 grade with no corresponding deterioration (≥1 grade worsening) in the fellow eye at Week 24. Denominator is the number of subjects with diplopia at Baseline.&#xD;
The Subjective Diplopia Score is a clinical measure of diplopia severity on a grade scale of 0 to 3: 0=no diplopia; 1=intermittent (diplopia in primary position of gaze, when tired or when first awakening); 2=inconstant (diplopia at extremes of gaze); 3=constant (continuous diplopia in primary or reading position).</description>
          <population>Intent-to-treat population: all randomized participants with diplopia at baseline in the study eye.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.6"/>
                    <measurement group_id="O2" value="67.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.001</p_value>
            <p_value_desc>Two-sided p-value calculated assuming the test statistic was distributed as a standard normal random variable.</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Stratified difference in percentages</param_type>
            <param_value>39.29</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>12.11</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>15.55</ci_lower_limit>
            <ci_upper_limit>63.02</ci_upper_limit>
            <estimate_desc>Stratified difference is a weighted average of the difference within each stratum. Estimates from the 2 strata (tobacco user, tobacco non-user) were combined with CMH weights.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score to Week 24</title>
        <description>The GO-QoL is a 16-item self-administered questionnaire divided into 2 subsets and used to assess the perceived effects of TED by the subjects on (i) their daily physical activity as it relates to visual function, and (ii) psychosocial functioning. The range of the GO-QoL overall transformed scores is 0 to 100, where higher values correspond to better quality of life.</description>
        <time_frame>Baseline, up to Week 24</time_frame>
        <population>Intent-to-treat population: all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Eight infusions of placebo q3W for a total of 21 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Teprotumumab 20 mg/kg</title>
            <description>Eight infusions of teprotumumab q3W for a total of 21 weeks. Teprotumumab 10 mg/kg administered on Day 1 and teprotumumab 20 mg/kg administered q3W for the remaining 7 infusions.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score to Week 24</title>
          <description>The GO-QoL is a 16-item self-administered questionnaire divided into 2 subsets and used to assess the perceived effects of TED by the subjects on (i) their daily physical activity as it relates to visual function, and (ii) psychosocial functioning. The range of the GO-QoL overall transformed scores is 0 to 100, where higher values correspond to better quality of life.</description>
          <population>Intent-to-treat population: all randomized participants.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.43" spread="2.102"/>
                    <measurement group_id="O2" value="13.79" spread="2.074"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>Results obtained from an MMRM with an unstructured covariance matrix including the following terms: Baseline value, tobacco use status, treatment group, visit, visit-by-treatment interaction and visit-by-Baseline-value interaction.</p_value_desc>
            <method>mixed model for repeated measures (MMRM)</method>
            <param_type>Difference in LS mean</param_type>
            <param_value>9.36</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>2.651</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>4.08</ci_lower_limit>
            <ci_upper_limit>14.64</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Eight infusions of placebo q3W for a total of 21 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Teprotumumab 20 mg/kg</title>
          <description>Eight infusions of teprotumumab q3W for a total of 21 weeks. Teprotumumab 10 mg/kg administered on Day 1 and teprotumumab 20 mg/kg administered q3W for the remaining 7 infusions.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 20.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Visual field defect</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 20.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="37" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain Upper</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle Spasms</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Amenorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Madarosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Horizon requests that any Investigator/institution that plans on presenting or publishing results provide written notification of their request a minimum of 60 days prior to presentation or publication. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsors' Intellectual Property rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Suzy Hammel</name_or_title>
      <organization>Horizon Pharma USA, Inc.</organization>
      <phone>866-479-6742</phone>
      <email>clinicaltrials@horizontherapeutics.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03298867
org study id: HZNP-TEP-301
secondary id: 2017-002763-18
nct id: NCT03298867
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The overall objective is to investigate the efficacy, tolerability, and safety of
      teprotumumab (a fully human monoclonal antibody [mAb] inhibitor of the insulin-like growth
      factor-1 receptor [IGF-1R]) administered once every 3 weeks (q3W) for 21 weeks with a final
      assessment at Week 24, in comparison to placebo, in the treatment of participants with
      moderate-to-severe active thyroid eye disease (TED).
This is a randomized, double-masked, placebo-controlled, parallel-group, multicenter study.
      Approximately 76 participants (38/group) who meet the study eligibility criteria will be
      randomized on Day 1 in a 1:1 ratio (stratified by tobacco use status) to receive 8 infusions
      of teprotumumab or placebo q3W. All participants will enter a 24-week double-masked Treatment
      Period, during which study drug will be infused on Day 1 (Baseline), and Weeks 3, 6, 9, 12,
      15, 18, and 21 (with a final visit at Week 24). All study drug dosing will be performed at
      the clinic under the supervision of clinic staff. On each dosing day, scheduled assessments
      (except for adverse event [AE] and concomitant medication use monitoring, which will be
      monitored throughout the clinic visit) will be completed prior to study drug dosing.

      At the end of the double-masked Treatment Period (Week 24), participants who are proptosis
      non-responders (study eye has < 2 mm decrease in proptosis) will be eligible to enter an
      open-label extension study in which participants receive 8 infusions of teprotumumab in an
      open-label fashion.

      At Week 24, proptosis responders, as well as non-responders who choose not to enroll in the
      open-label extension study, will enter a 48-week Follow-Up Period, during which study drug
      will not be administered and clinic visits are scheduled for Weeks 28, 36, 48, 60, and 72.
      Participants who are considered responders at Week 24 but who meet criteria for re-treatment
      due to relapse during the Follow-Up Period may enroll in the open-label extension study.

      Participants who complete the Week 72 Visit will be contacted 6 and 12 months later via phone
      or email by research staff to enquire if any treatment for TED has been received since last
      study contact.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage of Participants Who Were Proptosis Responders at Week 24
time frame: Week 24
description: Proptosis responders were defined as participants with a ≥2 mm reduction from Baseline in proptosis in the study eye, without deterioration (≥2 mm increase) of proptosis in the fellow eye at Week 24.
measure: Percentage of Participants Who Were Overall Responders at Week 24
time frame: Week 24
description: Overall responders were defined as participants with a ≥2 mm reduction in proptosis AND a ≥2 point reduction in Clinical Activity Score (CAS) from Baseline in the study eye, without deterioration (≥2 mm increase in proptosis or ≥2 point increase in CAS) in the fellow eye at Week 24.
The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/ Graves' Ophthalmopathy or Orbitopathy (TED/GO); 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (ignore "equivocal" redness); 6. Chemosis; 7. Inflammation of caruncle or plica. Each item is scored (1=present; 0=absent) and scores for each item are summed for total score of 0 (no clinical activity) to 7 (most clinical activity).
measure: Percentage of Participants Who Were CAS Categorical Responders at Week 24 (Study Eye)
time frame: Week 24
description: CAS categorical responders were defined as participants with a reduction to a CAS of 0 or 1 (no or minimal inflammatory symptoms) in study eye.
The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/ Graves' Ophthalmopathy or Orbitopathy (TED/GO); 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (ignore "equivocal" redness); 6. Chemosis; 7. Inflammation of caruncle or plica. Each item is scored (1=present; 0=absent) and scores for each item are summed for total score of 0 (no inflammatory symptoms) to 7 (most inflammatory symptoms).
measure: Change From Baseline in Proptosis to Week 24 (Study Eye)
time frame: Baseline, up to Week 24
measure: Percentage of Participants Who Were Diplopia Responders at Week 24
time frame: Week 24
description: Diplopia responders were defined as participants with Baseline diplopia Subjective Diplopia Score grade >0 in the study eye who had a reduction of ≥1 grade with no corresponding deterioration (≥1 grade worsening) in the fellow eye at Week 24. Denominator is the number of subjects with diplopia at Baseline.
The Subjective Diplopia Score is a clinical measure of diplopia severity on a grade scale of 0 to 3: 0=no diplopia; 1=intermittent (diplopia in primary position of gaze, when tired or when first awakening); 2=inconstant (diplopia at extremes of gaze); 3=constant (continuous diplopia in primary or reading position).
measure: Change From Baseline in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score to Week 24
time frame: Baseline, up to Week 24
description: The GO-QoL is a 16-item self-administered questionnaire divided into 2 subsets and used to assess the perceived effects of TED by the subjects on (i) their daily physical activity as it relates to visual function, and (ii) psychosocial functioning. The range of the GO-QoL overall transformed scores is 0 to 100, where higher values correspond to better quality of life.
arm group label: Teprotumumab 20 mg/kg
arm group type: Active Comparator
description: Approximately 38 participants will receive 8 infusions of teprotumumab q3W for a total of 21 weeks. Teprotumumab 10 mg/kg will be administered on Day 1 and teprotumumab 20 mg/kg will be administered q3W for the remaining 7 infusions.
arm group label: Placebo
arm group type: Placebo Comparator
description: Approximately 38 participants will receive 8 infusions of placebo q3W for a total of 21 weeks.
intervention type: Biological
intervention name: Teprotumumab
description: Teprotumumab is a fully human anti-IGF-1R mAb. Teprotumumab will be provided in single-dose 20 mL glass vials as a freeze-dried powder. Each vial of teprotumumab must be reconstituted with 10 mL of water for injection. Reconstituted teprotumumab solution must be further diluted in 0.9% (w/v) sodium chloride (NaCl) solution prior to administration. Teprotumumab will be administered in 100 mL or 250 mL infusion bags (100 mL infusion bags for doses up to 1800 mg and 250 mL infusion bags for doses > 1800 mg).
arm group label: Teprotumumab 20 mg/kg
other name: HZN-001
intervention type: Other
intervention name: Placebo
description: Placebo will consist of normal saline (0.9% NaCl) solution and will be administered in 100 mL or 250 mL infusion bags, as would be appropriate, per weight-based dosing volumes (100 mL infusion bags for doses up to 1800 mg and 250 mL infusion bags for doses > 1800 mg).
arm group label: Placebo
other name: Saline solution
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Raymond Douglas, MD, PhD
role: Principal Investigator
affiliation: Cedars-Sinai Medical Center
last name: George Kahaly, MD, PhD
role: Principal Investigator
affiliation: Johannes Gutenberg University Medical Center
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country: Germany
country: Italy
country: United States
url: https://www.tepezza.com/
description: Related Info
citation: Douglas RS, Kahaly GJ, Patel A, Sile S, Thompson EHZ, Perdok R, Fleming JC, Fowler BT, Marcocci C, Marino M, Antonelli A, Dailey R, Harris GJ, Eckstein A, Schiffman J, Tang R, Nelson C, Salvi M, Wester S, Sherman JW, Vescio T, Holt RJ, Smith TJ. Teprotumumab for the Treatment of Active Thyroid Eye Disease. N Engl J Med. 2020 Jan 23;382(4):341-352. doi: 10.1056/NEJMoa1910434.
PMID: 31971679
responsible party type: Sponsor
mesh term: Eye Diseases
mesh term: Graves Ophthalmopathy
mesh term: Thyroid Diseases
sharing ipd: Undecided
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