<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/NCT03307447</url>
  </required_header>
  <id_info>
    <org_study_id>#1617</org_study_id>
    <nct_id>NCT03307447</nct_id>
  </id_info>
  <brief_title>Secukinumab Therapy for the Treatment of Moderate to Severe Plaque Psoriasis With Response Monitoring Using Optical Coherence Tomography (OCT).</brief_title>
  <official_title>Secukinumab Therapy for the Treatment of Moderate to Severe Plaque Psoriasis With Response Monitoring Using Optical Coherence Tomography (OCT).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Narrows Institute for Biomedical Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Narrows Institute for Biomedical Research</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase IV, single-center, open label, single arm study in which a group of 30&#xD;
      subjects with moderate to severe plaque psoriasis will receive secukinumab therapy.&#xD;
      Non-invasive imaging with optical coherence tomography (OCT) will be used to monitor the&#xD;
      resolution of psoriatic plaques with treatment in comparison to observed clinical&#xD;
      improvements. Early subclinical finding will be used to elucidate drug mechanism of action.&#xD;
      Assessment will be based on intrasubject comparisons, and all findings will be compared to&#xD;
      patients baseline imaging.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Secukinumab, an anti-IL-17A monoclonal antibody, is an effective treatment for moderate to&#xD;
      severe plaque psoriasis.While there is an abundance of clinical data in the literature&#xD;
      supporting the clinical efficacy of this therapy, there is limited data on early disease&#xD;
      clearance and other histologic findings elucidating a drug mechanism of action.&#xD;
      Hyper-proliferation of the epidermis and inflammation of dermis seen in psoriasis are thought&#xD;
      to be due to persistent T-cell activation and production of several pro-inflammatory&#xD;
      cytokines by dermal immune reaction. Therefore, with treatments with immunomodulatory&#xD;
      effects, such as Secukinumab, monitoring markers of inflammation, angiogenesis, and collagen&#xD;
      synthesis would be useful in establishing mechanism of action. While a skin biopsy can show&#xD;
      these findings at one moment in time, it does not allow for repetitive monitoring overtime.&#xD;
      The investigators propose the use of non-invasive imaging with Optical Coherence Tomography&#xD;
      (OCT) to demonstrate histologic features of plaque psoriasis not clinically evident. Upon&#xD;
      completion of the study, the investigators will assess when OCT improvements of psoriasis&#xD;
      treatment are detectable and how these findings correlate to observed clinical improvements.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">December 19, 2017</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">September 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Elucidate drug mechanism of action by monitoring morphologic changes in lesional vs. perilesional psoriatic plaques using optical coherence tomography (OCT).</measure>
    <time_frame>week 12</time_frame>
    <description>Lesional and peri-lesional skin will be monitored using OCT for improvement from baseline by measuring changes epidermal, dermal and DEJ, as well as changes in vasculature.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare timing of subclinical improvement on OCT to the proportion of patients who achieve a reduction in PASI score by at least 75% (PASI 75) and/or score of 0 or 2-point improvement on the IGA (mod 2011) by week 12.</measure>
    <time_frame>week 12</time_frame>
    <description>The proportion of subjects who have a reduction of 75% or more from baseline in the psoriasis area-and-severity index score (PASI 75) or achieve a score of 0 on IGA, or at least a 2 point improvement, at week 12.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the onset/timing of subclinical improvement on OCT imaging to patients who achieve a 90% or 100% (PASI 90 and PASI 100) improvement from baseline in the PASI</measure>
    <time_frame>week 16</time_frame>
    <description>a. To compare the onset/timing of subclinical improvement on OCT imaging to patients who achieve a 90% or 100% (PASI 90 and PASI 100) improvement from baseline in the PASI by week 16</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Psoriasis Vulgaris</condition>
  <arm_group>
    <arm_group_label>Treatment arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cosentyx (Secukinumab) 300 mg subcutaneous injection at weeks 0, 1, 2, 3 and 4 followed by every 4 weeks until 16 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Secukinumab</intervention_name>
    <description>Secukinumab 300 mg subcutaneous injection</description>
    <arm_group_label>Treatment arm</arm_group_label>
    <other_name>cosentyx</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female subject at least 18 years of age with a diagnosis of moderate to severe&#xD;
             chronic plaque psoriasis vulgaris for at least 6 months.&#xD;
&#xD;
          2. Subjects must be candidates for systemic therapy and have at least moderate to severe&#xD;
             psoriasis, as defined by the Psoriasis Area and Severity Index (PASI) score: body&#xD;
             surface area (BSA) involvement &gt;10% , PASI &gt;12 and/or IGA modified (mod 2011) score of&#xD;
             3 (&quot;moderate&quot;) or 4 (&quot;severe&quot;). [2-4]&#xD;
&#xD;
          3. Patients must be naïve to prior biologic treatment&#xD;
&#xD;
          4. Subject is able to provide written informed consent and comply with the requirements&#xD;
             of this study protocol.&#xD;
&#xD;
          5. Subjects who are women of childbearing potential must have a negative urine pregnancy&#xD;
             test at screening and must be practicing an adequate, medically acceptable method of&#xD;
             birth control for at least 30 days before Day 0 and at least 6 months after the last&#xD;
             study drug administration. Acceptable methods of birth control include intrauterine&#xD;
             device (IUD); oral, transdermal, implanted or injected hormonal contraceptives (must&#xD;
             have been initiated at least 1 month before entering the study); tubal ligation;&#xD;
             abstinence and barrier methods with spermicide. Otherwise, if not of childbearing&#xD;
             potential, subjects must: have a sterile or vasectomized partner; have had a&#xD;
             hysterectomy, a bilateral oophorectomy or be clinically diagnosed infertile; or be in&#xD;
             a menopausal state for at least a year.&#xD;
&#xD;
          6. Tuberculin purified protein derivative (PPD) or QuantiFERON TB-Gold test (QFT)&#xD;
             negative at the time of screening, or if patient has a history of positive PPD or&#xD;
             QuantiFERON, he/she has completed the appropriate prophylaxis.&#xD;
&#xD;
          7. Subject is judged to be in good general health as determined by the principal&#xD;
             investigator based upon the results of medical history, laboratory profile, and&#xD;
             physical examination.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with guttate, erythrodermic, exfoliative, or pustular psoriasis, other skin&#xD;
             conditions affecting the treatment area, severe hepatic disorders or severe renal&#xD;
             insufficiency&#xD;
&#xD;
          2. Have received systemic psoriasis treatments (such as psoralen and PUVA light therapy,&#xD;
             cyclosporine, corticosteroids, methotrexate, retinoids, mycophenolate, hydroxyurea,&#xD;
             azathioprine, sirolimus) or phototherapy within the previous 4 weeks; or have had&#xD;
             topical therapy within the previous 2 weeks.&#xD;
&#xD;
          3. Have received any biologic agent for the treatment of psoriasis, including etanercept,&#xD;
             infliximab or adalimumab, alefacept, ustekinumab, or any other biologic agent&#xD;
&#xD;
          4. Use of other drugs with potential effect on psoriasis, such as beta blockers,&#xD;
             antimalarials, angiotensin-converting enzyme inhibitors, and lithium, are allowed,&#xD;
             provided that treatment was not initiated and the dosage did not change during the&#xD;
             trial.&#xD;
&#xD;
          5. Any subject who is pregnant or refuses to practice an acceptable method of birth&#xD;
             control (as stated in inclusion criterion # 4)&#xD;
&#xD;
          6. History of an ongoing, chronic or recurrent infectious disease, or evidence of&#xD;
             tuberculosis infection as defined by a positive tuberculin purified protein derivative&#xD;
             (PPD) or QuantiFERON TB-Gold test (QFT) at screening. Subjects with a positive or&#xD;
             indeterminate PPD or QFT test may participate in the study if a full tuberculosis work&#xD;
             up (according to local practice/guidelines) is completed within 12 weeks prior to&#xD;
             randomization and establishes conclusively that the subject has no evidence of active&#xD;
             tuberculosis. If presence of latent tuberculosis is established, then treatment must&#xD;
             have been initiated at least for 4 weeks prior to randomization and the course of&#xD;
             prophylaxis is planned to be completed.&#xD;
&#xD;
          7. Active Crohn's disease&#xD;
&#xD;
          8. History of significant allergies or intolerances&#xD;
&#xD;
          9. Imumunocompromised patients, including Subjects with a history of TB, HIV, Hepatitis B&#xD;
             or Hepatitis C infections&#xD;
&#xD;
         10. Have had live vaccination within 12 weeks prior to study&#xD;
&#xD;
         11. Have evidence of active infection, such as fever, within 5 days of dosing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Bethanne Wenzel</last_name>
    <phone>(718) 836-6600</phone>
    <phone_ext>8924</phone_ext>
    <email>bethanne.wenzel@va.gov</email>
  </overall_contact>
  <location>
    <facility>
      <name>VA NY Harbor Healthcare System</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11209</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bethanne Wenzel</last_name>
      <phone>718-836-6600</phone>
      <email>Bethanne.wenzel@va.gov</email>
    </contact>
    <investigator>
      <last_name>Orit Markowitz, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Daniel Siegel, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>October 6, 2017</study_first_submitted>
  <study_first_submitted_qc>October 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <last_update_submitted>August 31, 2021</last_update_submitted>
  <last_update_submitted_qc>August 31, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>optical coherence tomography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psoriasis</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/NCT03307447
org study id: #1617
nct id: NCT03307447
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a phase IV, single-center, open label, single arm study in which a group of 30
      subjects with moderate to severe plaque psoriasis will receive secukinumab therapy.
      Non-invasive imaging with optical coherence tomography (OCT) will be used to monitor the
      resolution of psoriatic plaques with treatment in comparison to observed clinical
      improvements. Early subclinical finding will be used to elucidate drug mechanism of action.
      Assessment will be based on intrasubject comparisons, and all findings will be compared to
      patients baseline imaging.
Secukinumab, an anti-IL-17A monoclonal antibody, is an effective treatment for moderate to
      severe plaque psoriasis.While there is an abundance of clinical data in the literature
      supporting the clinical efficacy of this therapy, there is limited data on early disease
      clearance and other histologic findings elucidating a drug mechanism of action.
      Hyper-proliferation of the epidermis and inflammation of dermis seen in psoriasis are thought
      to be due to persistent T-cell activation and production of several pro-inflammatory
      cytokines by dermal immune reaction. Therefore, with treatments with immunomodulatory
      effects, such as Secukinumab, monitoring markers of inflammation, angiogenesis, and collagen
      synthesis would be useful in establishing mechanism of action. While a skin biopsy can show
      these findings at one moment in time, it does not allow for repetitive monitoring overtime.
      The investigators propose the use of non-invasive imaging with Optical Coherence Tomography
      (OCT) to demonstrate histologic features of plaque psoriasis not clinically evident. Upon
      completion of the study, the investigators will assess when OCT improvements of psoriasis
      treatment are detectable and how these findings correlate to observed clinical improvements.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Elucidate drug mechanism of action by monitoring morphologic changes in lesional vs. perilesional psoriatic plaques using optical coherence tomography (OCT).
time frame: week 12
description: Lesional and peri-lesional skin will be monitored using OCT for improvement from baseline by measuring changes epidermal, dermal and DEJ, as well as changes in vasculature.
measure: Compare timing of subclinical improvement on OCT to the proportion of patients who achieve a reduction in PASI score by at least 75% (PASI 75) and/or score of 0 or 2-point improvement on the IGA (mod 2011) by week 12.
time frame: week 12
description: The proportion of subjects who have a reduction of 75% or more from baseline in the psoriasis area-and-severity index score (PASI 75) or achieve a score of 0 on IGA, or at least a 2 point improvement, at week 12.
measure: Compare the onset/timing of subclinical improvement on OCT imaging to patients who achieve a 90% or 100% (PASI 90 and PASI 100) improvement from baseline in the PASI
time frame: week 16
description: a. To compare the onset/timing of subclinical improvement on OCT imaging to patients who achieve a 90% or 100% (PASI 90 and PASI 100) improvement from baseline in the PASI by week 16
arm group label: Treatment arm
arm group type: Experimental
description: Cosentyx (Secukinumab) 300 mg subcutaneous injection at weeks 0, 1, 2, 3 and 4 followed by every 4 weeks until 16 weeks
intervention type: Drug
intervention name: Secukinumab
description: Secukinumab 300 mg subcutaneous injection
arm group label: Treatment arm
other name: cosentyx
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bethanne Wenzel
phone: (718) 836-6600
phone ext: 8924
email: bethanne.wenzel@va.gov
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Psoriasis
sharing ipd: Undecided