<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/NCT03020199</url>
  </required_header>
  <id_info>
    <org_study_id>CAIN457A2322</org_study_id>
    <nct_id>NCT03020199</nct_id>
  </id_info>
  <brief_title>Study of the Efficacy of Early Intervention With Secukinumab 300 mg s.c. Compared to Narrow-band UVB in Patients With New-onset Moderate to Severe Plaque Psoriasis</brief_title>
  <acronym>STEPin</acronym>
  <official_title>A Randomized, Multicenter STudy to Evaluate the Effect of Secukinumab 300 mg s.c. Administered During 52 Weeks to Patients Suffering From New-onset Moderate to Severe Plaque Psoriasis as Early Intervention Compared to Standard Treatment With Narrow-band UVB (STEPIn Study)</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>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether early intervention with subcutaneous (s.c.)&#xD;
      secukinumab 300 mg in patients with new-onset moderate to severe plaque psoriasis may lead to&#xD;
      prolonged symptom free periods by preventing reactivation of old lesions or ultimately&#xD;
      totally hindering the occurrence of new lesions, i.e., changing the natural course of the&#xD;
      disease (Main Study).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The overall study population (Main Study and Mechanistic Sub-study) will consist of a total&#xD;
      of 205 male and female patients aged between 18 and 40 years inclusive.&#xD;
&#xD;
      Main Study The Main Study will be conducted in patients with new-onset moderate to severe&#xD;
      plaque psoriasis not previously treated with any systemic treatment or phototherapy. A total&#xD;
      of 160 patients will be randomized to Arm A1 or Arm B1 in approximately 50 sites worldwide.&#xD;
      Since a maximum screening failure rate of 20% is expected, approximately 200 patients will be&#xD;
      screened.&#xD;
&#xD;
      Mechanistic Sub-study Any patient who consents can participate in the Mechanistic Sub-study.&#xD;
      Patients with new-onset plaque psoriasis will be randomized to Arm A1b, Arm A2, or Arm B1b,&#xD;
      those with chronic plaque psoriasis will be randomized to Arm C1 and Arm C2 (15 patients&#xD;
      each). For Arm A1b or Arm B1b, the first 15 patients will be included on a first come first&#xD;
      serve basis.&#xD;
&#xD;
      Safety assessments :Physical examination, Vital signs, Height and body weight, Laboratory&#xD;
      evaluations (hematology, clinical chemistry, high-sensitivity C-reactive protein),&#xD;
      Electrocardiogram, Pregnancy, Adverse events&#xD;
&#xD;
      Data Analysis The primary efficacy variable is the proportion of patients who achieve PASI 90&#xD;
      at Week 52. The analysis for the primary objective will be based on the full analysis set.&#xD;
      For the primary analysis, the following hypothesis testing will be performed: H01: psec =&#xD;
      pnbUVB versus HA1: psec ≠ pnbUVB The primary analysis method for PASI 90 response at Week 52&#xD;
      will use an exact logistic regression model with treatment as an explanatory variable and&#xD;
      baseline PASI score as covariate. The key secondary variable is the proportion of all&#xD;
      randomized patients who achieve PASI 90 at Week 104. In order to reduce selection bias, all&#xD;
      patients who do not achieve PASI 90 at Week 52 will also be included in the analysis at Week&#xD;
      104 using the PASI improvement obtained at Week 104 only.&#xD;
&#xD;
      For the key secondary analysis, the following hypothesis testing will be performed:&#xD;
&#xD;
      H02: p*sec = p*nbUVB versus HA2: p*sec ≠ p*nbUVB&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 27, 2017</start_date>
  <completion_date type="Anticipated">August 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">August 30, 2024</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The primary efficacy variable is the proportion of patients who achieve Pain Assessment Severity Index (PASI) 90 at Week 52. PASI is measured by dermatologist usung a PASI measurement scale.</measure>
    <time_frame>52 weeks</time_frame>
    <description>To demonstrate that early treatment with secukinumab 300 mg s.c. (Arm A1) is superior to standard of care treatment with nb-UVB (Arm B1) in patients with new-onset moderate to severe plaque psoriasis with respect to patients achieving ≥ 90% improvement (reduction) in psoriasis area and severity index (PASI 90) response at Week 52.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The key secondary variable is the proportion of all randomized patients who achieve PASI 90 at Week 104</measure>
    <time_frame>104 weeks</time_frame>
    <description>To evaluate the superiority of early treatment with secukinumab (Arm A1) versus nb-UVB (Arm B1) based on the proportion of all randomized patients who achieve at least PASI 90 at Week 104.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">196</enrollment>
  <condition>Plaque Psoriasis</condition>
  <arm_group>
    <arm_group_label>A1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>80 patients (65 in Arm A1a and 15 in Arm A1b) with new-onset psoriasis will receive 300 mg secukinumab by s.c. injection at baseline, Weeks 1, 2, 3, 4 and then every 4 weeks until Week 48 inclusive.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>80 patients (65 in Arm B1a and 15 in Arm B1b) with new-onset psoriasis will receive 1 or 2 cycles of nb-UVB of 12 weeks each with a maximum break of 28 weeks between cycles (patients with PASI 90 at Week 40 will not receive a second treatment cycle).Only during the first 4 weeks of each cycle, nb-UVB treatment should be applied in combination with topical calcipotriol 50 μg/g and betamethasone 0.5 mg/g.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>secukinumab 300 mg s.c. administered at baseline, once weekly at Weeks 1, 2, 3 and 4; and thereafter every 4 weeks until Week 100 inclusive (last dose administered at Week 100)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>secukinumab 300 mg s.c. administered at baseline, once weekly at Weeks 1, 2, 3 and 4; and thereafter every 4 weeks until Week 48 inclusive (last dose administered at Week 48)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>secukinumab 300 mg s.c. administered at baseline, once weekly at Weeks 1, 2, 3 and 4; and thereafter every 4 weeks until Week 100 inclusive (last dose administered at Week 100)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Secukinumab</intervention_name>
    <description>Secukinumab (AIN457) 300 mg will be administered in an open-label fashion according to label as 2 s.c. injections of secukinumab 150 mg (1-mL liquid formulation in a pre-filled syringe). Each 300-mg dose will be provided as 2 pre-filled syringes of 150-mg secukinumab in a single box. Each syringe is labeled as AIN457 150 mg/1 mL.</description>
    <arm_group_label>A1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>nbUVB</intervention_name>
    <description>Narrow-band UVB applied in 1 or 2 cycles, each comprising a period of 12 weeks with 2 to 3 treatment sessions per week totaling 24 to 36 sessions per cycle. The application will be performed according to the investigational site's protocol, taking into account the patient's skin type. A maximum dose of 3 J/cm2 on the body and 1 J/cm2 on the face is recommended</description>
    <arm_group_label>B1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Secukinumab</intervention_name>
    <description>Secukinumab (AIN457) 300 mg will be administered in an open-label fashion according to label as 2 s.c. injections of secukinumab 150 mg (1-mL liquid formulation in a pre-filled syringe). Each 300-mg dose will be provided as 2 pre-filled syringes of 150-mg secukinumab in a single box. Each syringe is labeled as AIN457 150 mg/1 mL</description>
    <arm_group_label>A2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Secukinumab</intervention_name>
    <description>Secukinumab (AIN457) 300 mg will be administered in an open-label fashion according to label as 2 s.c. injections of secukinumab 150 mg (1-mL liquid formulation in a pre-filled syringe). Each 300-mg dose will be provided as 2 pre-filled syringes of 150-mg secukinumab in a single box. Each syringe is labeled as AIN457 150 mg/1 mL</description>
    <arm_group_label>C1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Secukinumab</intervention_name>
    <description>Secukinumab (AIN457) 300 mg will be administered in an open-label fashion according to label as 2 s.c. injections of secukinumab 150 mg (1-mL liquid formulation in a pre-filled syringe). Each 300-mg dose will be provided as 2 pre-filled syringes of 150-mg secukinumab in a single box. Each syringe is labeled as AIN457 150 mg/1 mL</description>
    <arm_group_label>C2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Calcipotriol</intervention_name>
    <description>Its a topical treatment for Psoriasis. the concentration it is used is 50mcg/g</description>
    <arm_group_label>B1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Betamethasone</intervention_name>
    <description>this is topical cream which is used in 0.5mg/g concentration</description>
    <arm_group_label>B1</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Able to understand and communicate with the investigator, willing and capable to&#xD;
             comply with all study procedures, and provide written signed and dated informed&#xD;
             consent (personally or by a witness) before any assessment is performed&#xD;
&#xD;
          -  Aged 18 to 40 years inclusive&#xD;
&#xD;
          -  New-onset plaque psoriasis with appearance of the first psoriasis plaques within the&#xD;
             last 12 months before randomization and naïve to any systemic treatment and&#xD;
             phototherapy (Arms A1, A2 and Arm B1)&#xD;
&#xD;
          -  Chronic plaque psoriasis with appearance of the first psoriasis symptoms 5 years or&#xD;
             longer and intolerance or inadequate response to phototherapy or any systemic&#xD;
             treatment including biologicals, except for IL-17A inhibitors (Arm C1 and Arm C2)&#xD;
&#xD;
          -  Moderate to severe plaque psoriasis defined at screening and baseline by PASI ≥ 10,&#xD;
             and body surface area (BSA) ≥ 10%, and investigator's global assessment (IGA mod 2011)&#xD;
             ≥ 3&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Forms of psoriasis other than plaque-type (e.g., pustular, erythrodermic, guttate,&#xD;
             light sensitive, and drug induced)&#xD;
&#xD;
          -  Ongoing use of prohibited treatments&#xD;
&#xD;
          -  Previous treatment with phototherapy or any systemic treatment&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women&#xD;
&#xD;
          -  Women of childbearing potential, defined as all women physiologically capable of&#xD;
             becoming pregnant, unless they are using effective methods of contraception during the&#xD;
             Treatment Epoch or longer if required by locally-approved prescribing information&#xD;
             (e.g., 20 weeks in the EU)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ciudad Autonoma de Bs As</city>
        <state>Buenos Aires</state>
        <zip>1181</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1425DKG</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pleven</city>
        <zip>5800</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Plovdiv</city>
        <zip>4002</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sofia</city>
        <zip>1407</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sofia</city>
        <zip>1632</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Markham</city>
        <state>Ontario</state>
        <zip>L3P 1X2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sudbury</city>
        <state>Ontario</state>
        <zip>P3C 1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Aarhus</city>
        <zip>8000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tallinn</city>
        <zip>10138</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tallinn</city>
        <zip>13419</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tartu</city>
        <zip>51014</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tampere</city>
        <zip>33100</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Turku</city>
        <zip>FIN-20100</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>10789</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Erlangen</city>
        <zip>91054</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Frankfurt</city>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nyíregyháza</city>
        <zip>4400</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Szolnok</city>
        <zip>5000</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bialystok</city>
        <zip>15-879</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-094</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Gdansk</city>
        <zip>80-803</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Krakow</city>
        <zip>31-070</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lodz</city>
        <zip>90-436</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lodz</city>
        <zip>90-647</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barcelona</city>
        <state>Catalunya</state>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barcelona</city>
        <state>Catalunya</state>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Alicante</city>
        <state>Comunidad Valenciana</state>
        <zip>03010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Valencia</city>
        <state>Comunidad Valenciana</state>
        <zip>46014</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Alcorcon</city>
        <state>Madrid</state>
        <zip>28922</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Las Palmas de Gran Canaria</city>
        <zip>35010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Madrid</city>
        <zip>28031</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Goethenburg</city>
        <zip>413 45</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Malmo</city>
        <zip>214 28</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lausanne</city>
        <zip>CH-1011</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bradford</city>
        <state>West Yorkshire</state>
        <zip>BD5 0NA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Leeds</city>
        <state>West Yorkshire</state>
        <zip>LS7 4SA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>London</city>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Salford</city>
        <zip>M6 8HD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Bulgaria</country>
    <country>Canada</country>
    <country>Denmark</country>
    <country>Estonia</country>
    <country>Finland</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Switzerland</country>
    <country>United Kingdom</country>
  </location_countries>
  <removed_countries>
    <country>Czechia</country>
    <country>Norway</country>
    <country>Romania</country>
  </removed_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>September 23, 2016</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <last_update_submitted>June 6, 2023</last_update_submitted>
  <last_update_submitted_qc>June 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Psoriasis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psoriasis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Betamethasone</mesh_term>
    <mesh_term>Calcipotriene</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03020199
org study id: CAIN457A2322
nct id: NCT03020199
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine whether early intervention with subcutaneous (s.c.)
      secukinumab 300 mg in patients with new-onset moderate to severe plaque psoriasis may lead to
      prolonged symptom free periods by preventing reactivation of old lesions or ultimately
      totally hindering the occurrence of new lesions, i.e., changing the natural course of the
      disease (Main Study).
The overall study population (Main Study and Mechanistic Sub-study) will consist of a total
      of 205 male and female patients aged between 18 and 40 years inclusive.

      Main Study The Main Study will be conducted in patients with new-onset moderate to severe
      plaque psoriasis not previously treated with any systemic treatment or phototherapy. A total
      of 160 patients will be randomized to Arm A1 or Arm B1 in approximately 50 sites worldwide.
      Since a maximum screening failure rate of 20% is expected, approximately 200 patients will be
      screened.

      Mechanistic Sub-study Any patient who consents can participate in the Mechanistic Sub-study.
      Patients with new-onset plaque psoriasis will be randomized to Arm A1b, Arm A2, or Arm B1b,
      those with chronic plaque psoriasis will be randomized to Arm C1 and Arm C2 (15 patients
      each). For Arm A1b or Arm B1b, the first 15 patients will be included on a first come first
      serve basis.

      Safety assessments :Physical examination, Vital signs, Height and body weight, Laboratory
      evaluations (hematology, clinical chemistry, high-sensitivity C-reactive protein),
      Electrocardiogram, Pregnancy, Adverse events

      Data Analysis The primary efficacy variable is the proportion of patients who achieve PASI 90
      at Week 52. The analysis for the primary objective will be based on the full analysis set.
      For the primary analysis, the following hypothesis testing will be performed: H01: psec =
      pnbUVB versus HA1: psec ≠ pnbUVB The primary analysis method for PASI 90 response at Week 52
      will use an exact logistic regression model with treatment as an explanatory variable and
      baseline PASI score as covariate. The key secondary variable is the proportion of all
      randomized patients who achieve PASI 90 at Week 104. In order to reduce selection bias, all
      patients who do not achieve PASI 90 at Week 52 will also be included in the analysis at Week
      104 using the PASI improvement obtained at Week 104 only.

      For the key secondary analysis, the following hypothesis testing will be performed:

      H02: p*sec = p*nbUVB versus HA2: p*sec ≠ p*nbUVB
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The primary efficacy variable is the proportion of patients who achieve Pain Assessment Severity Index (PASI) 90 at Week 52. PASI is measured by dermatologist usung a PASI measurement scale.
time frame: 52 weeks
description: To demonstrate that early treatment with secukinumab 300 mg s.c. (Arm A1) is superior to standard of care treatment with nb-UVB (Arm B1) in patients with new-onset moderate to severe plaque psoriasis with respect to patients achieving ≥ 90% improvement (reduction) in psoriasis area and severity index (PASI 90) response at Week 52.
measure: The key secondary variable is the proportion of all randomized patients who achieve PASI 90 at Week 104
time frame: 104 weeks
description: To evaluate the superiority of early treatment with secukinumab (Arm A1) versus nb-UVB (Arm B1) based on the proportion of all randomized patients who achieve at least PASI 90 at Week 104.
arm group label: A1
arm group type: Experimental
description: 80 patients (65 in Arm A1a and 15 in Arm A1b) with new-onset psoriasis will receive 300 mg secukinumab by s.c. injection at baseline, Weeks 1, 2, 3, 4 and then every 4 weeks until Week 48 inclusive.
arm group label: B1
arm group type: Active Comparator
description: 80 patients (65 in Arm B1a and 15 in Arm B1b) with new-onset psoriasis will receive 1 or 2 cycles of nb-UVB of 12 weeks each with a maximum break of 28 weeks between cycles (patients with PASI 90 at Week 40 will not receive a second treatment cycle).Only during the first 4 weeks of each cycle, nb-UVB treatment should be applied in combination with topical calcipotriol 50 μg/g and betamethasone 0.5 mg/g.
arm group label: A2
arm group type: Experimental
description: secukinumab 300 mg s.c. administered at baseline, once weekly at Weeks 1, 2, 3 and 4; and thereafter every 4 weeks until Week 100 inclusive (last dose administered at Week 100)
arm group label: C1
arm group type: Experimental
description: secukinumab 300 mg s.c. administered at baseline, once weekly at Weeks 1, 2, 3 and 4; and thereafter every 4 weeks until Week 48 inclusive (last dose administered at Week 48)
arm group label: C2
arm group type: Experimental
description: secukinumab 300 mg s.c. administered at baseline, once weekly at Weeks 1, 2, 3 and 4; and thereafter every 4 weeks until Week 100 inclusive (last dose administered at Week 100)
intervention type: Biological
intervention name: Secukinumab
description: Secukinumab (AIN457) 300 mg will be administered in an open-label fashion according to label as 2 s.c. injections of secukinumab 150 mg (1-mL liquid formulation in a pre-filled syringe). Each 300-mg dose will be provided as 2 pre-filled syringes of 150-mg secukinumab in a single box. Each syringe is labeled as AIN457 150 mg/1 mL.
arm group label: A1
intervention type: Radiation
intervention name: nbUVB
description: Narrow-band UVB applied in 1 or 2 cycles, each comprising a period of 12 weeks with 2 to 3 treatment sessions per week totaling 24 to 36 sessions per cycle. The application will be performed according to the investigational site's protocol, taking into account the patient's skin type. A maximum dose of 3 J/cm2 on the body and 1 J/cm2 on the face is recommended
arm group label: B1
intervention type: Biological
intervention name: Secukinumab
description: Secukinumab (AIN457) 300 mg will be administered in an open-label fashion according to label as 2 s.c. injections of secukinumab 150 mg (1-mL liquid formulation in a pre-filled syringe). Each 300-mg dose will be provided as 2 pre-filled syringes of 150-mg secukinumab in a single box. Each syringe is labeled as AIN457 150 mg/1 mL
arm group label: A2
intervention type: Biological
intervention name: Secukinumab
description: Secukinumab (AIN457) 300 mg will be administered in an open-label fashion according to label as 2 s.c. injections of secukinumab 150 mg (1-mL liquid formulation in a pre-filled syringe). Each 300-mg dose will be provided as 2 pre-filled syringes of 150-mg secukinumab in a single box. Each syringe is labeled as AIN457 150 mg/1 mL
arm group label: C1
intervention type: Biological
intervention name: Secukinumab
description: Secukinumab (AIN457) 300 mg will be administered in an open-label fashion according to label as 2 s.c. injections of secukinumab 150 mg (1-mL liquid formulation in a pre-filled syringe). Each 300-mg dose will be provided as 2 pre-filled syringes of 150-mg secukinumab in a single box. Each syringe is labeled as AIN457 150 mg/1 mL
arm group label: C2
intervention type: Drug
intervention name: Calcipotriol
description: Its a topical treatment for Psoriasis. the concentration it is used is 50mcg/g
arm group label: B1
intervention type: Drug
intervention name: Betamethasone
description: this is topical cream which is used in 0.5mg/g concentration
arm group label: B1
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
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country: Argentina
country: Bulgaria
country: Canada
country: Denmark
country: Estonia
country: Finland
country: Germany
country: Hungary
country: Poland
country: Spain
country: Sweden
country: Switzerland
country: United Kingdom
country: Czechia
country: Norway
country: Romania
responsible party type: Sponsor
mesh term: Psoriasis
mesh term: Betamethasone
mesh term: Calcipotriene
mesh term: Antibodies, Monoclonal
sharing ipd: No