<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/NCT04478994</url>
  </required_header>
  <id_info>
    <org_study_id>HZNP-TEP-001</org_study_id>
    <nct_id>NCT04478994</nct_id>
  </id_info>
  <brief_title>A Study With TEPEZZA in Patients With Diffuse Cutaneous Systemic Sclerosis (dcSSc)</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled, Repeat-Dose, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics, and Explore Efficacy of TEPEZZA in Patients With Diffuse Cutaneous Systemic Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Horizon Therapeutics USA, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Horizon Pharma USA, Inc.</source>
  <oversight_info>
    <has_dmc>No</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 safety, tolerability and effect on insulin-like&#xD;
      growth factor-1 (IGF-1), inflammatory and fibrotic biomarkers of TEPEZZA (teprotumumab-trbw,&#xD;
      HZN-001), a fully human monoclonal antibody (mAb) inhibitor of the IGF-1 receptor (IGF-1R),&#xD;
      administered once every 3 weeks (q3W) for 24 weeks in the treatment of participants with&#xD;
      diffuse cutaneous systemic sclerosis (dcSSc).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-blind, placebo-controlled, repeat-dose, multicenter study.&#xD;
      Participants will be screened for the study within 4 weeks prior to the Baseline (Day 1)&#xD;
      Visit. Approximately 25 participants who meet the study eligibility criteria will be&#xD;
      randomized on Day 1 in a 3:2 ratio to receive 8 infusions of TEPEZZA or placebo q3W. During&#xD;
      the 24-week double-blind Treatment Period, study drug will be infused on Day 1 (Baseline) and&#xD;
      Weeks 3, 6, 9, 12, 15, 18 and 21 with a comprehensive visit at Week 24 (end of treatment). On&#xD;
      each dosing day, scheduled assessments (except for Adverse Events [AE] and concomitant&#xD;
      medication use monitoring, which will be monitored throughout the clinic visit) will be&#xD;
      completed prior to study drug infusions.&#xD;
&#xD;
      At the end of the Treatment Period (Week 24), participants will enter a 24-week Follow-up&#xD;
      Period, during which study drug will not be administered and a clinic visit will be scheduled&#xD;
      for Weeks 28, 36 and 48. A phone call or email at Weeks 32 and 42 will occur to inquire how&#xD;
      the participant is doing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Poor enrollment&#xD;
  </why_stopped>
  <start_date type="Actual">November 17, 2021</start_date>
  <completion_date type="Actual">December 8, 2022</completion_date>
  <primary_completion_date type="Actual">November 29, 2022</primary_completion_date>
  <phase>Phase 1</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>Proportion of participants who experience a treatment emergent adverse event (TEAE) through Week 24 in subjects with dcSSc.</measure>
    <time_frame>Week 24</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Diffuse Cutaneous Systemic Sclerosis</condition>
  <arm_group>
    <arm_group_label>TEPEZZA 20mg/kg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Approximately 15 participants will receive 8 infusions of TEPEZZA q3W for a total of 21 weeks. TEPEZZA 10mg/kg will be administered on Day 1 and TEPEZZA 20mg/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 10 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>TEPEZZA</intervention_name>
    <description>TEPEZZA is a fully human anti-IGF-1R mAb. TEPEZZA will be provided in single-dose 20 mL glass vials as a freeze-dried powder. Each vial of TEPEZZA must be reconstituted with 10 mL of water for injection. Reconstituted TEPEZZA solution must be further diluted in 0.9% (w/v) sodium chloride (NaCl) solution prior to administration. TEPEZZA 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>TEPEZZA 20mg/kg</arm_group_label>
    <other_name>teprotumumab-trbw</other_name>
    <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 between the ages of 18 and 80 years, inclusive, at Screening.&#xD;
&#xD;
          3. Meets the 2013 American College of Rheumatology/European League Against Rheumatism&#xD;
             classification criteria for systemic sclerosis (SSc) with a total score of ≥9.&#xD;
&#xD;
          4. Classified as having skin involvement proximal to elbow, knee, face and neck.&#xD;
&#xD;
          5. At the time of enrollment, no more than 60 months must have elapsed since the onset of&#xD;
             the first dcSSc manifestations, other than Raynaud's phenomenon.&#xD;
&#xD;
          6. Skin thickening from dcSSc in the forearm suitable for repeat biopsy.&#xD;
&#xD;
          7. mRSS units ≥10 and ≤45 at Screening.&#xD;
&#xD;
          8. Participant will be allowed to take CellCept® (mycophenolate mofetil) up to 3 g/day or&#xD;
             Myfortic® (mycophenolic acid) up to 2.14 g/day and low-dose prednisone (≤10 mg/day or&#xD;
             equivalent dosing of glucocorticoids). Participants taking CellCept or Myfortic have&#xD;
             been doing so for ≥20 weeks and the dose must have been stable for ≥16 weeks prior to&#xD;
             the Day 1 Visit. Prednisone must have been at a stable dose for ≥4 weeks prior to the&#xD;
             Day 1 Visit.&#xD;
&#xD;
          9. Diabetic participants must have glycated hemoglobin (HbA1c) ≤8.0%, with no new&#xD;
             diabetic medication (oral or insulin) or more than a 10% change in the dose of a&#xD;
             currently prescribed diabetic medication within 60 days prior to Screening.&#xD;
&#xD;
         10. Women of childbearing potential (including those with an onset of menopause &lt;2 years&#xD;
             prior to Screening, nontherapy-induced amenorrhea for &lt;12 months prior to Screening or&#xD;
             not surgically sterile [absence of ovaries and/or uterus]) must have a negative serum&#xD;
             pregnancy test at Screening and negative urine pregnancy tests at all&#xD;
             protocol-specified timepoints (i.e., prior to each dose and throughout the&#xD;
             participant's participation in the Follow-up Period); participants who are sexually&#xD;
             active with a non vasectomized male partner must agree to use 2 reliable forms of&#xD;
             contraception during the trial, one of which is recommended to be hormonal, such as an&#xD;
             oral contraceptive. Hormonal contraception must be started at least one full cycle&#xD;
             prior to Baseline and continue for 180 days after the last dose of study drug. Highly&#xD;
             effective contraceptive methods (with a failure rate &lt;1% per year), when used&#xD;
             consistently and correctly, include implants, injectables, combined oral&#xD;
             contraceptives, some intrauterine devices, sexual abstinence or vasectomized partner.&#xD;
&#xD;
         11. Willing and able to comply with the prescribed treatment protocol and evaluations for&#xD;
             the duration of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Diagnosed with limited cutaneous SSc or sine scleroderma.&#xD;
&#xD;
          2. Diagnosed with other autoimmune connective tissue diseases, except for fibromyalgia,&#xD;
             scleroderma associated myopathy and Sjogren's syndrome.&#xD;
&#xD;
          3. Scleroderma renal crisis diagnosed within 6 months of the Screening Visit,&#xD;
             characterized by abrupt onset of hypertension and acute kidney injury.&#xD;
&#xD;
          4. Forced vital capacity (FVC) &lt;50% predicted, diffusing capacity of the lungs for carbon&#xD;
             monoxide (DLCO) &lt;40% predicted or pulmonary arterial hypertension (PAH) by right heart&#xD;
             catheterization requiring treatment with more than one oral PAH approved therapy or&#xD;
             parenteral therapy (intermittent use of phosphodiesterase-5 inhibitors are allowed for&#xD;
             erectile dysfunction and/or Raynaud's phenomenon/digital ulcers).&#xD;
&#xD;
          5. Corticosteroid use for conditions other than dcSSc within 4 weeks prior to Screening&#xD;
             (topical steroids for dermatological conditions and inhaled steroids are allowed).&#xD;
&#xD;
          6. Previous treatment with rituximab (Rituxan® or MabThera®) within 12 months prior to&#xD;
             the first infusion.&#xD;
&#xD;
          7. Use of a non-steroidal immunosuppressive agent, cytotoxic or anti-fibrotic drug within&#xD;
             4 weeks of Screening, including cyclophosphamide, azathioprine (Imuran®), methotrexate&#xD;
             or other immunosuppressive or cytotoxic medication. Exceptions are mycophenolate&#xD;
             mofetil (CellCept) and mycophenolic acid (Myfortic), which are permitted according to&#xD;
             inclusion criterion 8, and anti-malarials (e.g., hydroxychloroquine [Plaquenil®]).&#xD;
&#xD;
          8. Use of biologics or small molecules approved for rheumatoid arthritis, psoriatic&#xD;
             arthritis and other rheumatic diseases within 4 weeks prior to Screening.&#xD;
&#xD;
          9. Use of an investigational agent for any condition within 90 days or 5 half-lives,&#xD;
             whichever is longer, prior to Screening or anticipated use during the course of the&#xD;
             trial.&#xD;
&#xD;
         10. Malignant condition in the past 5 years (except successfully treated basal/squamous&#xD;
             cell carcinoma of the skin or cervical cancer in situ).&#xD;
&#xD;
         11. Pregnant or lactating women.&#xD;
&#xD;
         12. Current drug or alcohol abuse or history of either within the previous 2 years, in the&#xD;
             opinion of the Investigator or as reported by the participant.&#xD;
&#xD;
         13. Biopsy-proven or clinically suspected inflammatory bowel disease (e.g., diarrhea with&#xD;
             or without blood or rectal bleeding associated with abdominal pain or cramping/colic,&#xD;
             urgency, tenesmus or incontinence for more than 4 weeks without a confirmed&#xD;
             alternative diagnosis OR endoscopic or radiologic evidence of enteritis/colitis&#xD;
             without a confirmed alternative diagnosis).&#xD;
&#xD;
         14. Known hypersensitivity to any of the components of TEPEZZA or prior hypersensitivity&#xD;
             reactions to mAbs.&#xD;
&#xD;
         15. Previous enrollment in this study or participation in a prior teprotumumab-trbw&#xD;
             clinical trial.&#xD;
&#xD;
         16. Human immunodeficiency virus, untreated or positive viral load for hepatitis C or&#xD;
             hepatitis B infections.&#xD;
&#xD;
         17. Previous organ transplant (including allogeneic and autologous marrow transplant).&#xD;
&#xD;
         18. Alanine aminotransferase or aspartate aminotransferase &gt;2.5 times the upper limit of&#xD;
             normal or estimated glomerular filtration rate of &lt;30 mL/min/1.73m^2 at Screening.&#xD;
&#xD;
         19. Platelets &lt;100×10^3/µL.&#xD;
&#xD;
         20. Hemoglobin &lt;8 g/dL.&#xD;
&#xD;
         21. Any other condition that, in the opinion of the Investigator, would preclude inclusion&#xD;
             in the study.&#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>Saba Sile, MD</last_name>
    <role>Study Director</role>
    <affiliation>Horizon Therapeutics USA, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCLA Division of Rheumatology</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>900095-1670</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Arthritis Care Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale North Haven Medical Center</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06473</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Johns Hopkins Bayview Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Toledo Medical Center</name>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <zip>43614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Physicians Center for AutoImmunity</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>July 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>December 19, 2022</last_update_submitted>
  <last_update_submitted_qc>December 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Scleroderma, Systemic</mesh_term>
    <mesh_term>Scleroderma, Diffuse</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04478994
org study id: HZNP-TEP-001
nct id: NCT04478994
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The overall objective is to investigate the safety, tolerability and effect on insulin-like
      growth factor-1 (IGF-1), inflammatory and fibrotic biomarkers of TEPEZZA (teprotumumab-trbw,
      HZN-001), a fully human monoclonal antibody (mAb) inhibitor of the IGF-1 receptor (IGF-1R),
      administered once every 3 weeks (q3W) for 24 weeks in the treatment of participants with
      diffuse cutaneous systemic sclerosis (dcSSc).
This is a randomized, double-blind, placebo-controlled, repeat-dose, multicenter study.
      Participants will be screened for the study within 4 weeks prior to the Baseline (Day 1)
      Visit. Approximately 25 participants who meet the study eligibility criteria will be
      randomized on Day 1 in a 3:2 ratio to receive 8 infusions of TEPEZZA or placebo q3W. During
      the 24-week double-blind Treatment Period, study drug will be infused on Day 1 (Baseline) and
      Weeks 3, 6, 9, 12, 15, 18 and 21 with a comprehensive visit at Week 24 (end of treatment). On
      each dosing day, scheduled assessments (except for Adverse Events [AE] and concomitant
      medication use monitoring, which will be monitored throughout the clinic visit) will be
      completed prior to study drug infusions.

      At the end of the Treatment Period (Week 24), participants will enter a 24-week Follow-up
      Period, during which study drug will not be administered and a clinic visit will be scheduled
      for Weeks 28, 36 and 48. A phone call or email at Weeks 32 and 42 will occur to inquire how
      the participant is doing.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Proportion of participants who experience a treatment emergent adverse event (TEAE) through Week 24 in subjects with dcSSc.
time frame: Week 24
arm group label: TEPEZZA 20mg/kg
arm group type: Active Comparator
description: Approximately 15 participants will receive 8 infusions of TEPEZZA q3W for a total of 21 weeks. TEPEZZA 10mg/kg will be administered on Day 1 and TEPEZZA 20mg/kg will be administered q3W for the remaining 7 infusions.
arm group label: Placebo
arm group type: Placebo Comparator
description: Approximately 10 participants will receive 8 infusions of placebo q3W for a total of 21 weeks.
intervention type: Biological
intervention name: TEPEZZA
description: TEPEZZA is a fully human anti-IGF-1R mAb. TEPEZZA will be provided in single-dose 20 mL glass vials as a freeze-dried powder. Each vial of TEPEZZA must be reconstituted with 10 mL of water for injection. Reconstituted TEPEZZA solution must be further diluted in 0.9% (w/v) sodium chloride (NaCl) solution prior to administration. TEPEZZA 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: TEPEZZA 20mg/kg
other name: teprotumumab-trbw
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: Saba Sile, MD
role: Study Director
affiliation: Horizon Therapeutics USA, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Scleroderma, Systemic
mesh term: Scleroderma, Diffuse
mesh term: Sclerosis
sharing ipd: Undecided