<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/NCT04488185</url>
  </required_header>
  <id_info>
    <org_study_id>CAIN457AUS26</org_study_id>
    <nct_id>NCT04488185</nct_id>
  </id_info>
  <brief_title>An Efficacy Study of Secukinumab in Plaque Psoriasis Patients With Subclinical Psoriatic Arthritis as Measured by Musculoskeletal Ultrasound</brief_title>
  <acronym>INTERCEPT</acronym>
  <official_title>An Exploratory, Randomized, Double-blind, Parallel-group, Multicenter Study to Compare Secukinumab 300 mg With Placebo After 16 Weeks of Treatment in Adults With Moderate to Severe Plaque Psoriasis and Subclinical Enthesitis Measured by Musculoskeletal Ultrasound</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</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>
      Given the role of IL-17 in the development of entheseal-driven pathology, a therapeutic&#xD;
      strategy aimed at blocking IL-17 would be a logical option for the treatment of subclinical&#xD;
      enthesitis in psoriasis patients. This study will be the first randomized trial of a biologic&#xD;
      therapy versus placebo in participants with plaque psoriasis and subclinical psoriatic&#xD;
      arthritis, using musculoskeletal ultrasound.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of this study is to estimate the difference in effect between&#xD;
      secukinumab 300 mg s.c. and placebo, based on change from baseline to Week 16 in the OMERACT&#xD;
      ultrasound enthesitis score.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    low recruitment&#xD;
  </why_stopped>
  <start_date type="Actual">November 2, 2020</start_date>
  <completion_date type="Actual">March 24, 2021</completion_date>
  <primary_completion_date type="Actual">March 24, 2021</primary_completion_date>
  <phase>Phase 4</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>Change from Baseline in the Outcome Measures in Rheumatology (OMERACT) ultrasound enthesitis score</measure>
    <time_frame>Baseline and Week 16</time_frame>
    <description>Twelve (12) entheses (bilateral AT, LE, PP, DP, PA, QT) will be scored in terms of inflammatory and morphological components according to the OMERACT enthesitis composite semi-quantitative scale (0 to 3). The lowest OMERACT score a participant can have at baseline is 2 (based on Inclusion Criterion number 6, which requires at least 2 points in the B-mode or the Doppler mode in at least one enthesis). The highest OMERACT score expected at baseline will be 72, assuming that each of the 12 entheses assessed shows a maximum of 3 points in the gray scale score, and a maximum of 3 points in the Doppler score. The largest change expected from baseline to Week 16 is -60 points (improvement). This assumes that the presence of structural changes (calcifications, enthesophytes and erosions) may add a maximum of 12 points to the score, and it may not be modifiable with study treatment during the study period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) ultrasound enthesitis score</measure>
    <time_frame>Baseline and Week 16</time_frame>
    <description>Sixteen (16) entheses (bilateral AT, LE, PP, DP, PA, QT, SS, TT) will be scored in terms of inflammatory components according with the GRAPPA ultrasound enthesitis score. The lowest GRAPPA score a participant may have at baseline is 2 (based on Inclusion Criterion number 6, which requires at least 2 points in the B-mode or the Doppler mode in at least 1 enthesis). The highest GRAPPA score expected at baseline is 248, assuming the maximum score that could be assigned to each enthesis. The largest change expected from baseline to Week 16 is -136 points (improvement). This value assumes that the presence of structural changes (calcifications, enthesophytes, and erosions) may add a maximum of 136 points to the score, and it may not be modifiable with study treatment during the study period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in the PsASon13 unilateral ultrasound composite score of synovitis</measure>
    <time_frame>Baseline and Week 16</time_frame>
    <description>Joints examined by the PsASon13 unilateral ultrasound composite score: Small finger joints: MCP2, MCP5, H-PIP1, H-PIP2, H-PIP3; Distal interphalangeal finger joints: H-DIP3; Small joints of feet: MTP1, MTP5, F-PIP1; Distal interphalangeal joints of feet: F-DIP2, F-DIP3; Large joints: wrist and knee. Lowest score a participant may have at baseline is 0. Highest score a participant may have at baseline is 184 (5 small finger joints, each ranging from 0 to 18; 1 distal interphalangeal finger joint, each ranging from 0 to 16; 3 small joints of feet, each ranging from 0 to 12; 2 distal interphalangeal joints of feet, each ranging from 0 to 12; 1 wrist ranging from 0 to 12; and 1 knee ranging from 0 to 6). Largest change expected from baseline to Week 16 is -118 points (improvement). This assumes that the presence of structural changes (erosions and osteophytes) may add a maximum of 66 points to the score and it may not be modifiable with study treatment during the study period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants who achieve complete resolution of enthesitis based on OMERACT criteria (yes, no)</measure>
    <time_frame>Baseline and Week 16</time_frame>
    <description>Proportion of participants experiencing complete resolution of their enthesitis based on Change from Baseline in the Outcome Measures in Rheumatology (OMERACT) score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants who achieve Psoriasis Area and Severity Index 90 (PASI 90) (yes, no)</measure>
    <time_frame>Baseline and Week 16</time_frame>
    <description>Psoriasis Area Severity Index 90&#xD;
Scores range from 0 to 72. A score of more than 10 generally translates to &quot;moderate-to-severe&quot;. Usually, the higher your PASI score, the lower the quality of life. A PASI 90 is at least a 90% improvement (reduction) in PASI score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants who achieve Psoriasis Area and Severity Index 100 (PASI 100) (yes, no)</measure>
    <time_frame>Baseline and Week 16</time_frame>
    <description>Psoriasis Area Severity Index 100&#xD;
Scores range from 0 to 72. A score of more than 10 generally translates to &quot;moderate-to-severe&quot;. Usually, the higher your PASI score, the lower the quality of life. A PASI 100 is a complete clearing of psoriasis (PASI score = 0).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants who achieve Investigator's Global Assessment modified 2011 (IGA mod 2011) score of 0 or 1 (yes, no)</measure>
    <time_frame>Baseline and Week 16</time_frame>
    <description>The IGA mod 2011 scale is a visual assessment that consists of a score ranging from 0 (clear) to 4 (severe). Skin rated a 4 is bright red in color with marked plaque elevation and is dominated by thick, non-tenacious scale. For a treatment to be considered successful, the affected area must receive a score of 0 or 1 and experience a two-point improvement from Baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Body Surface Area (BSA)</measure>
    <time_frame>Baseline and Week 16</time_frame>
    <description>The total percentage of body surface area affected by psoriasis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Dermatology Life Quality Index (DLQI) score</measure>
    <time_frame>Baseline and Week 16</time_frame>
    <description>A 10-item measure to assess health-related quality of life in adults with skin diseases. Scores range from 0-30 with a higher score being less quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants who achieve Dermatology Life Quality Index (DLQI) score of 0 or 1 (yes, no)</measure>
    <time_frame>Baseline and Week 16</time_frame>
    <description>A 10-item measure to assess health-related quality of life in adults with skin diseases. Scores range from 0-30 with a higher score being less quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in HAQ-DI score</measure>
    <time_frame>Baseline and Week 16</time_frame>
    <description>Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question scale assessing functional ability. The final HAQ-DI score ranges from 0 (no problems functioning) to 3 (not able to function).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants who achieve HAQ-DI change from baseline ≤ -0.35 (yes, no)</measure>
    <time_frame>Baseline and Week 16</time_frame>
    <description>Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question scale assessing functional ability. The final HAQ-DI score ranges from 0 (no problems functioning) to 3 (not able to function).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Psoriasis</condition>
  <arm_group>
    <arm_group_label>Secukinumab 300mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Randomized in a 2:1 ratio to secukinumab or placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Randomized in a 2:1 ratio to secukinumab or placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Secukinumab 300 mg</intervention_name>
    <description>Secukinumab 300 mg administered s.c. (2 single-use prefilled syringes of 150 mg/mL), on Days 1, 8, 15, 22, 29, 57, 85.</description>
    <arm_group_label>Secukinumab 300mg</arm_group_label>
    <other_name>AIN457</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo administered s.c. (2 single-use prefilled 1 mL syringes) on Days 1, 8, 15, 22, 29, 57, 85.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical diagnosis of chronic plaque-type psoriasis confirmed through physical&#xD;
             examination by a dermatologist, with at least six months of clinical history prior to&#xD;
             the baseline visit&#xD;
&#xD;
          -  Moderate to severe plaque psoriasis at baseline as defined as:&#xD;
&#xD;
          -  ≥ 10 % Body Surface Area (BSA) involvement, or&#xD;
&#xD;
          -  ≥ 3% to &lt;10% Body Surface Area with involvement of special regions (nails, scalp, or&#xD;
             intertriginous skin), or with a history of psoriatic arthritis in a parent&#xD;
&#xD;
        Candidate for systemic therapy, defined as having psoriasis inadequately controlled by&#xD;
        current topical and/or systemic treatment(s) (including topical corticosteroids),&#xD;
        phototherapy, or previous systemic therapies&#xD;
&#xD;
        Presence of sonographic enthesitis at screening, in at least one enthesis, defined by the&#xD;
        presence of at least abnormal thickening and hypoechogenicity of the tendon insertion, with&#xD;
        or without presence of Doppler signal (Grade 0-3), or by the presence of grade ≥ 2 Doppler&#xD;
        signal, independent of gray scale abnormalities&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of PsA as per CASPAR confirmed by a rheumatologist (including the presence&#xD;
             of inflammatory pain in entheses or joints), and any other known rheumatological&#xD;
             disease affecting the assessed joints&#xD;
&#xD;
          -  Exposure to any IL-17 or IL-23(p19) inhibitor for the treatment of psoriasis (approved&#xD;
             or investigational) within twelve months prior to screening, or exposure to any&#xD;
             inhibitors of TNF-ɑ and IL12/23 within six months prior to screening&#xD;
&#xD;
          -  Previous exposure to non-biologic systemic therapy for psoriasis, including&#xD;
             methotrexate, PDE-4 inhibitors, or systemic corticosteroids within 12 weeks or 5&#xD;
             half-lives (whichever is longer) prior to screening&#xD;
&#xD;
          -  A degree of obesity that impedes proper ultrasound examination of entheses and joints&#xD;
&#xD;
          -  Forms of diagnosed psoriasis other than chronic plaque psoriasis (e.g., erythrodermic,&#xD;
             generalized or localized pustular psoriasis, or new onset guttate psoriasis)&#xD;
&#xD;
        Other protocol-defined inclusion/exclusion criteria may apply&#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_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
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    <citation>Acquacalda E, Albert C, Montaudie H, Fontas E, Danre A, Roux CH, Breuil V, Lacour JP, Passeron T, Ziegler LE. Ultrasound study of entheses in psoriasis patients with or without musculoskeletal symptoms: A prospective study. Joint Bone Spine. 2015 Jul;82(4):267-71. doi: 10.1016/j.jbspin.2015.01.016. Epub 2015 Apr 13.</citation>
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  <verification_date>March 2023</verification_date>
  <study_first_submitted>June 26, 2020</study_first_submitted>
  <study_first_submitted_qc>July 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2020</study_first_posted>
  <last_update_submitted>March 28, 2023</last_update_submitted>
  <last_update_submitted_qc>March 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Psoriasis</keyword>
  <keyword>Subclinical enthesitis</keyword>
  <keyword>secukinumab</keyword>
  <keyword>subclinical psoriatic arthritis</keyword>
  <keyword>Plaque psoriasis</keyword>
  <keyword>AIN457</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>Yes</sharing_ipd>
    <ipd_description>Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com</ipd_description>
  </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/NCT04488185
org study id: CAIN457AUS26
nct id: NCT04488185
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Given the role of IL-17 in the development of entheseal-driven pathology, a therapeutic
      strategy aimed at blocking IL-17 would be a logical option for the treatment of subclinical
      enthesitis in psoriasis patients. This study will be the first randomized trial of a biologic
      therapy versus placebo in participants with plaque psoriasis and subclinical psoriatic
      arthritis, using musculoskeletal ultrasound.
The primary objective of this study is to estimate the difference in effect between
      secukinumab 300 mg s.c. and placebo, based on change from baseline to Week 16 in the OMERACT
      ultrasound enthesitis score.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change from Baseline in the Outcome Measures in Rheumatology (OMERACT) ultrasound enthesitis score
time frame: Baseline and Week 16
description: Twelve (12) entheses (bilateral AT, LE, PP, DP, PA, QT) will be scored in terms of inflammatory and morphological components according to the OMERACT enthesitis composite semi-quantitative scale (0 to 3). The lowest OMERACT score a participant can have at baseline is 2 (based on Inclusion Criterion number 6, which requires at least 2 points in the B-mode or the Doppler mode in at least one enthesis). The highest OMERACT score expected at baseline will be 72, assuming that each of the 12 entheses assessed shows a maximum of 3 points in the gray scale score, and a maximum of 3 points in the Doppler score. The largest change expected from baseline to Week 16 is -60 points (improvement). This assumes that the presence of structural changes (calcifications, enthesophytes and erosions) may add a maximum of 12 points to the score, and it may not be modifiable with study treatment during the study period.
measure: Change from Baseline in the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) ultrasound enthesitis score
time frame: Baseline and Week 16
description: Sixteen (16) entheses (bilateral AT, LE, PP, DP, PA, QT, SS, TT) will be scored in terms of inflammatory components according with the GRAPPA ultrasound enthesitis score. The lowest GRAPPA score a participant may have at baseline is 2 (based on Inclusion Criterion number 6, which requires at least 2 points in the B-mode or the Doppler mode in at least 1 enthesis). The highest GRAPPA score expected at baseline is 248, assuming the maximum score that could be assigned to each enthesis. The largest change expected from baseline to Week 16 is -136 points (improvement). This value assumes that the presence of structural changes (calcifications, enthesophytes, and erosions) may add a maximum of 136 points to the score, and it may not be modifiable with study treatment during the study period.
measure: Change from Baseline in the PsASon13 unilateral ultrasound composite score of synovitis
time frame: Baseline and Week 16
description: Joints examined by the PsASon13 unilateral ultrasound composite score: Small finger joints: MCP2, MCP5, H-PIP1, H-PIP2, H-PIP3; Distal interphalangeal finger joints: H-DIP3; Small joints of feet: MTP1, MTP5, F-PIP1; Distal interphalangeal joints of feet: F-DIP2, F-DIP3; Large joints: wrist and knee. Lowest score a participant may have at baseline is 0. Highest score a participant may have at baseline is 184 (5 small finger joints, each ranging from 0 to 18; 1 distal interphalangeal finger joint, each ranging from 0 to 16; 3 small joints of feet, each ranging from 0 to 12; 2 distal interphalangeal joints of feet, each ranging from 0 to 12; 1 wrist ranging from 0 to 12; and 1 knee ranging from 0 to 6). Largest change expected from baseline to Week 16 is -118 points (improvement). This assumes that the presence of structural changes (erosions and osteophytes) may add a maximum of 66 points to the score and it may not be modifiable with study treatment during the study period.
measure: Number of participants who achieve complete resolution of enthesitis based on OMERACT criteria (yes, no)
time frame: Baseline and Week 16
description: Proportion of participants experiencing complete resolution of their enthesitis based on Change from Baseline in the Outcome Measures in Rheumatology (OMERACT) score
measure: Number of participants who achieve Psoriasis Area and Severity Index 90 (PASI 90) (yes, no)
time frame: Baseline and Week 16
description: Psoriasis Area Severity Index 90
Scores range from 0 to 72. A score of more than 10 generally translates to "moderate-to-severe". Usually, the higher your PASI score, the lower the quality of life. A PASI 90 is at least a 90% improvement (reduction) in PASI score.
measure: Number of participants who achieve Psoriasis Area and Severity Index 100 (PASI 100) (yes, no)
time frame: Baseline and Week 16
description: Psoriasis Area Severity Index 100
Scores range from 0 to 72. A score of more than 10 generally translates to "moderate-to-severe". Usually, the higher your PASI score, the lower the quality of life. A PASI 100 is a complete clearing of psoriasis (PASI score = 0).
measure: Number of participants who achieve Investigator's Global Assessment modified 2011 (IGA mod 2011) score of 0 or 1 (yes, no)
time frame: Baseline and Week 16
description: The IGA mod 2011 scale is a visual assessment that consists of a score ranging from 0 (clear) to 4 (severe). Skin rated a 4 is bright red in color with marked plaque elevation and is dominated by thick, non-tenacious scale. For a treatment to be considered successful, the affected area must receive a score of 0 or 1 and experience a two-point improvement from Baseline.
measure: Change from Baseline in Body Surface Area (BSA)
time frame: Baseline and Week 16
description: The total percentage of body surface area affected by psoriasis
measure: Change from Baseline in Dermatology Life Quality Index (DLQI) score
time frame: Baseline and Week 16
description: A 10-item measure to assess health-related quality of life in adults with skin diseases. Scores range from 0-30 with a higher score being less quality of life.
measure: Number of participants who achieve Dermatology Life Quality Index (DLQI) score of 0 or 1 (yes, no)
time frame: Baseline and Week 16
description: A 10-item measure to assess health-related quality of life in adults with skin diseases. Scores range from 0-30 with a higher score being less quality of life.
measure: Change from Baseline in HAQ-DI score
time frame: Baseline and Week 16
description: Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question scale assessing functional ability. The final HAQ-DI score ranges from 0 (no problems functioning) to 3 (not able to function).
measure: Number of participants who achieve HAQ-DI change from baseline ≤ -0.35 (yes, no)
time frame: Baseline and Week 16
description: Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question scale assessing functional ability. The final HAQ-DI score ranges from 0 (no problems functioning) to 3 (not able to function).
arm group label: Secukinumab 300mg
arm group type: Experimental
description: Randomized in a 2:1 ratio to secukinumab or placebo
arm group label: Placebo
arm group type: Placebo Comparator
description: Randomized in a 2:1 ratio to secukinumab or placebo
intervention type: Biological
intervention name: Secukinumab 300 mg
description: Secukinumab 300 mg administered s.c. (2 single-use prefilled syringes of 150 mg/mL), on Days 1, 8, 15, 22, 29, 57, 85.
arm group label: Secukinumab 300mg
other name: AIN457
intervention type: Other
intervention name: Placebo
description: Placebo administered s.c. (2 single-use prefilled 1 mL syringes) on Days 1, 8, 15, 22, 29, 57, 85.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
country: United States
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responsible party type: Sponsor
mesh term: Psoriasis
sharing ipd: Yes
ipd description: Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com