<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/NCT03791060</url>
  </required_header>
  <id_info>
    <org_study_id>2018P000634</org_study_id>
    <nct_id>NCT03791060</nct_id>
  </id_info>
  <brief_title>Secukinumab for NLD (Cosentyx) in Patients With Necrobiosis Lipoidica Diabeticorum (NLD)</brief_title>
  <official_title>An Open-label Proof of Concept Study Regarding the Use of Secukinumab (Cosentyx) in Patients With Necrobiosis Lipoidica Diabeticorum (NLD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beth Israel Deaconess Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Beth Israel Deaconess Medical Center</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study investigates the efficacy of secukinumab in necrobiosis lipoidica diabeticorum&#xD;
      (NLD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Necrobiosis lipoidica diabeticorum (NLD) is a rare granulomatous condition of the skin often&#xD;
      presenting with papules and eventually atrophic plaques, most commonly on the distal extensor&#xD;
      lower extremities, which can be painful and disfiguring. Currently no FDA-approved treatment&#xD;
      exists, and no well-established treatment algorithm has been described. Reports on successful&#xD;
      therapeutic interventions have generally been small and inconsistent.&#xD;
&#xD;
      Recent literature expanding on the previously poorly understood pathogenesis of NLD has&#xD;
      suggested a potential role for IL-17 in the development of this condition. Thus blockade of&#xD;
      IL-17 may be a potential therapeutic strategy in patients with NLD. Secukinumab (Cosentyx) is&#xD;
      a human monoclonal antibody that targets IL-17a and is FDA approved for the treatment of&#xD;
      psoriasis.&#xD;
&#xD;
      This open-label, proof of concept study regarding the use of Secukinumab in patients with NLD&#xD;
      may be a first step in elucidating and defining a treatment for this chronic and potentially&#xD;
      debilitating condition for which no FDA approved treatment currently exists.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study halted prematurely due COVID-19 pandemic and did not resume; participants are no longer&#xD;
    being examined or receiving intervention.&#xD;
  </why_stopped>
  <start_date type="Actual">April 3, 2019</start_date>
  <completion_date type="Actual">April 10, 2021</completion_date>
  <primary_completion_date type="Actual">January 17, 2021</primary_completion_date>
  <phase>Phase 2</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>Investigator Global Assessment Score</measure>
    <time_frame>24 weeks</time_frame>
    <description>Proportion of patients achieving remission or clinical improvement based on Investigator Global Assessment Score as measured at week 24.&#xD;
Score Description&#xD;
0. Completely clear: except for possible residual hyperpigmentation&#xD;
Almost clear: very significant clearance (about 90%); however, patchy remnants of dusky erythema and/or very small ulcerations&#xD;
Marked improvement: significant improvement (about 75%); however, a small amount of disease remaining (i.e. remaining ulcers, although have decreased in size, minimal erythema and/or active boarder)&#xD;
Moderate improvement: intermediate between slight and marked; representing about 50% improvement&#xD;
Slight improvement: some improvement (about 25%); however, significant disease remaining (i.e. remaining ulcers with only minor decrease in size, erythema or boarder activity)&#xD;
No change from baseline&#xD;
Worse</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Histology</measure>
    <time_frame>26 weeks</time_frame>
    <description>Proportion of subjects achieving improvement based upon histological score. The score is calculated by adding subscores as listed below, which will be evaluated by the dermatopathologist. Average of pre and post scores and overall change in score will be calculated and compared using a paired T-test.&#xD;
Inflammatory infiltrate (0, none; 1, slight; 2, moderate; 3, severe)&#xD;
collagen degeneration (0, none; 1, slight; 2, moderate; 3, severe)&#xD;
epithelioid histiocytes, (0, none; 1, slight; 2, moderate; 3, severe)&#xD;
qualitative expression of IL-17 (0, none; 1, slight; 2 moderate; 3, severe)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Score</measure>
    <time_frame>Assessed at week 1, 2, 3, 4, 8, 12, 16, 20, 25</time_frame>
    <description>Self-reported pain and stinging intensity during and directly after treatment with Secukinumab injections&#xD;
A Pain Score will be calculated based upon the Wong-Baker 10-point pain score, which has been widely used to rate pain in both children and adults and has also been used in dermatology clinical trials.&#xD;
Response based on an improvement from baseline in the Wong-Baker pain score at all scheduled time points will be calculated. We will compare pre and post treatment pain values and categorize patients as (i) Resolved (ii) Improved (iii) Stable (iv) Worsened</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dermatology Life Quality Index</measure>
    <time_frame>Assessed at week 1, 2, 3, 4, 8, 12, 16, 20, 25</time_frame>
    <description>Proportion of subjects improving based upon patient-reported outcomes The DLQI is a validated general dermatology questionnaire that consists of 10 items that assess subject health-related quality of life (daily activities, personal relationships, symptoms and feelings, leisure, work and school, and treatment) The DLQI is a psychometrically valid and reliable instrument that has been translated into several languages, and the DLQI total scores have been shown to be responsive to change. The minimally important difference for the DLQI has been estimated as a 2 to 5 point change from baseline.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Necrobiosis Lipoidica Diabeticorum</condition>
  <arm_group>
    <arm_group_label>Secukinumab Subcutaneous Injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>300 mg q weekly for 5 weeks followed by 300 mg q 4 weeks.&#xD;
Each subject will receive 300mg of Secukinumab by using 2 syringes of 150mg each as a subcutaneous injection at weeks 0,1,2,3,4 then every 4 weeks for a total of 9 doses over 24 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Secukinumab</intervention_name>
    <description>Secukinumab is selective for human IL-17A and potently neutralizes the bioactivity of this cytokine. IL-17A is the central cytokine in multiple autoimmune and inflammatory processes. It is being recognized as one of the principal pro-inflammatory cytokines in autoimmune diseases such as psoriasis, PsA and AS, uveitis and is thought to play a role in other inflammatory conditions.</description>
    <arm_group_label>Secukinumab Subcutaneous Injection</arm_group_label>
    <other_name>cosentyx</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults, age 18 and over&#xD;
&#xD;
          -  Previous diagnosis of biopsy-proven NLD&#xD;
&#xD;
          -  Active NLD lesions, defined as&#xD;
&#xD;
               -  clinical signs of inflammation, for example erythematous margins, sensations of&#xD;
                  itch, pain, dysaesthesia&#xD;
&#xD;
               -  lesions increasing in size or appearance of new lesions within the last 3 months&#xD;
&#xD;
               -  ulcerations&#xD;
&#xD;
          -  Subjects must be able to understand and communicate with the investigator and comply&#xD;
             with the requirements of the study and must give a written, signed and dated informed&#xD;
             consent before any study related activity is performed.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of an ongoing, chronic or recurrent infectious disease, or evidence of&#xD;
             tuberculosis infection as defined by a positive QuantiFERON TB-Gold test at screening.&#xD;
&#xD;
          -  Are currently pregnant, breastfeeding, or planning to get pregnant during the study.&#xD;
&#xD;
          -  Previous hypersensitivity reaction to secukinumab or to any of the components.&#xD;
&#xD;
          -  History of Inflammatory Bowel Disease (Crohn's Disease or Ulcerative Colitis)&#xD;
&#xD;
          -  Allergy to Latex&#xD;
&#xD;
          -  Currently on any other immunosuppressant systemic medication or within 28 days of&#xD;
             baseline visit&#xD;
&#xD;
          -  Women of child-bearing potential, defined as all women physiologically capable of&#xD;
             becoming pregnant, unwilling to use effective contraception during the study and for&#xD;
             16 weeks after stopping treatment.&#xD;
&#xD;
          -  Subjects with a serum creatinine level exceeding 176.8 μmol/L (2.0 mg/dL)&#xD;
&#xD;
          -  Screening total WBC count &lt;2,500/μL, or platelets &lt;100,000/μL or neutrophils &lt;1,500/μL&#xD;
             or hemoglobin &lt;8.5 g/dL&#xD;
&#xD;
          -  Known infection with HIV, hepatitis B or hepatitis C at screening or randomization.&#xD;
             Patients who are Hepatitis B Core antibody and/or Hep B Surface Antigen positive will&#xD;
             be excluded from this study. Patients who are Hepatitis C ab positive will also be&#xD;
             excluded from this study.&#xD;
&#xD;
          -  History of lymphoproliferative disease or any known malignancy or history of&#xD;
             malignancy of any organ system within the past 5 years (except for non-melanoma skin&#xD;
             cancer and carcinoma in situ of the cervix)&#xD;
&#xD;
          -  Are participating in another study using an investigational agent or procedure during&#xD;
             participation in this study or within 28 days prior to baseline visit.&#xD;
&#xD;
          -  Plans for administration of live vaccines during the study period or 6 weeks prior to&#xD;
             randomization&#xD;
&#xD;
          -  Any other procedural treatment for NLD with 28 days prior to baseline visit, including&#xD;
             phototherapy, surgical intervention, laser therapy, or cryotherapy.&#xD;
&#xD;
          -  Any other active skin disease or condition (e.g., bacterial, fungal or viral&#xD;
             infection) that may interfere with assessment of NLD;&#xD;
&#xD;
          -  Underlying condition (including, but not limited to metabolic, hematologic, renal,&#xD;
             hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal)&#xD;
             which in the opinion of the investigator significantly immunocompromises the subject&#xD;
             and/or places the subject at unacceptable risk for receiving an immunomodulatory&#xD;
             therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>110 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alexa Kimball, MD MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beth Israel Deaconess Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>December 21, 2018</study_first_submitted>
  <study_first_submitted_qc>December 31, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 2, 2019</study_first_posted>
  <last_update_submitted>February 4, 2022</last_update_submitted>
  <last_update_submitted_qc>February 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beth Israel Deaconess Medical Center</investigator_affiliation>
    <investigator_full_name>Alexa B Kimball</investigator_full_name>
    <investigator_title>MD, MPH</investigator_title>
  </responsible_party>
  <keyword>Necrobiosis lipoidica</keyword>
  <keyword>NLD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Necrobiotic Disorders</mesh_term>
    <mesh_term>Necrobiosis Lipoidica</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>July 13, 2022</submitted>
    <returned>August 3, 2022</returned>
    <submitted>September 7, 2022</submitted>
    <returned>October 5, 2022</returned>
    <submitted>July 19, 2023</submitted>
    <returned>August 8, 2023</returned>
  </pending_results>
  <!-- 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/NCT03791060
org study id: 2018P000634
nct id: NCT03791060
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This study investigates the efficacy of secukinumab in necrobiosis lipoidica diabeticorum
      (NLD).
Necrobiosis lipoidica diabeticorum (NLD) is a rare granulomatous condition of the skin often
      presenting with papules and eventually atrophic plaques, most commonly on the distal extensor
      lower extremities, which can be painful and disfiguring. Currently no FDA-approved treatment
      exists, and no well-established treatment algorithm has been described. Reports on successful
      therapeutic interventions have generally been small and inconsistent.

      Recent literature expanding on the previously poorly understood pathogenesis of NLD has
      suggested a potential role for IL-17 in the development of this condition. Thus blockade of
      IL-17 may be a potential therapeutic strategy in patients with NLD. Secukinumab (Cosentyx) is
      a human monoclonal antibody that targets IL-17a and is FDA approved for the treatment of
      psoriasis.

      This open-label, proof of concept study regarding the use of Secukinumab in patients with NLD
      may be a first step in elucidating and defining a treatment for this chronic and potentially
      debilitating condition for which no FDA approved treatment currently exists.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Investigator Global Assessment Score
time frame: 24 weeks
description: Proportion of patients achieving remission or clinical improvement based on Investigator Global Assessment Score as measured at week 24.
Score Description
0. Completely clear: except for possible residual hyperpigmentation
Almost clear: very significant clearance (about 90%); however, patchy remnants of dusky erythema and/or very small ulcerations
Marked improvement: significant improvement (about 75%); however, a small amount of disease remaining (i.e. remaining ulcers, although have decreased in size, minimal erythema and/or active boarder)
Moderate improvement: intermediate between slight and marked; representing about 50% improvement
Slight improvement: some improvement (about 25%); however, significant disease remaining (i.e. remaining ulcers with only minor decrease in size, erythema or boarder activity)
No change from baseline
Worse
measure: Histology
time frame: 26 weeks
description: Proportion of subjects achieving improvement based upon histological score. The score is calculated by adding subscores as listed below, which will be evaluated by the dermatopathologist. Average of pre and post scores and overall change in score will be calculated and compared using a paired T-test.
Inflammatory infiltrate (0, none; 1, slight; 2, moderate; 3, severe)
collagen degeneration (0, none; 1, slight; 2, moderate; 3, severe)
epithelioid histiocytes, (0, none; 1, slight; 2, moderate; 3, severe)
qualitative expression of IL-17 (0, none; 1, slight; 2 moderate; 3, severe)
measure: Pain Score
time frame: Assessed at week 1, 2, 3, 4, 8, 12, 16, 20, 25
description: Self-reported pain and stinging intensity during and directly after treatment with Secukinumab injections
A Pain Score will be calculated based upon the Wong-Baker 10-point pain score, which has been widely used to rate pain in both children and adults and has also been used in dermatology clinical trials.
Response based on an improvement from baseline in the Wong-Baker pain score at all scheduled time points will be calculated. We will compare pre and post treatment pain values and categorize patients as (i) Resolved (ii) Improved (iii) Stable (iv) Worsened
measure: Dermatology Life Quality Index
time frame: Assessed at week 1, 2, 3, 4, 8, 12, 16, 20, 25
description: Proportion of subjects improving based upon patient-reported outcomes The DLQI is a validated general dermatology questionnaire that consists of 10 items that assess subject health-related quality of life (daily activities, personal relationships, symptoms and feelings, leisure, work and school, and treatment) The DLQI is a psychometrically valid and reliable instrument that has been translated into several languages, and the DLQI total scores have been shown to be responsive to change. The minimally important difference for the DLQI has been estimated as a 2 to 5 point change from baseline.
arm group label: Secukinumab Subcutaneous Injection
arm group type: Experimental
description: 300 mg q weekly for 5 weeks followed by 300 mg q 4 weeks.
Each subject will receive 300mg of Secukinumab by using 2 syringes of 150mg each as a subcutaneous injection at weeks 0,1,2,3,4 then every 4 weeks for a total of 9 doses over 24 weeks.
intervention type: Drug
intervention name: Secukinumab
description: Secukinumab is selective for human IL-17A and potently neutralizes the bioactivity of this cytokine. IL-17A is the central cytokine in multiple autoimmune and inflammatory processes. It is being recognized as one of the principal pro-inflammatory cytokines in autoimmune diseases such as psoriasis, PsA and AS, uveitis and is thought to play a role in other inflammatory conditions.
arm group label: Secukinumab Subcutaneous Injection
other name: cosentyx
criteria: 
gender: All
minimum age: 18 Years
maximum age: 110 Years
healthy volunteers: No
last name: Alexa Kimball, MD MPH
role: Principal Investigator
affiliation: Beth Israel Deaconess Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Beth Israel Deaconess Medical Center
investigator full name: Alexa B Kimball
investigator title: MD, MPH
mesh term: Necrobiotic Disorders
mesh term: Necrobiosis Lipoidica
sharing ipd: No
submitted: July 13, 2022
returned: August 3, 2022
submitted: September 7, 2022
returned: October 5, 2022
submitted: July 19, 2023
returned: August 8, 2023