<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/NCT01726933</url>
  </required_header>
  <id_info>
    <org_study_id>M41008-1102</org_study_id>
    <secondary_id>2012-000055-13</secondary_id>
    <nct_id>NCT01726933</nct_id>
  </id_info>
  <brief_title>LAS41008 in Moderate to Severe Chronic Plaque Psoriasis</brief_title>
  <official_title>A Multi-center, Randomized, Double-blind, Three-arm, 16 Week, Adaptive Phase III Clinical Study to Investigate the Efficacy and Safety of LAS41008 vs LASW1835 and vs Placebo in Patients With Moderate to Severe Chronic Plaque Psoriasis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Almirall, S.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Almirall Hermal GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Harrison Clinical Research</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Almirall, S.A.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the study is to evaluate the efficacy and safety of LAS41008 in comparison to&#xD;
      active control and placebo in patients with moderate to severe chronic plaque psoriasis&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">November 2015</completion_date>
  <primary_completion_date type="Actual">October 2014</primary_completion_date>
  <phase>Phase 3</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PASI 75</measure>
    <time_frame>16 weeks</time_frame>
    <description>Reduction of PASI by 75% from baseline to week 16</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Physician Global Assessment, PGA</measure>
    <time_frame>16 weeks</time_frame>
    <description>Change in PGA from baseline to week 16</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Body Surface Area, BSA</measure>
    <time_frame>16 weeks</time_frame>
    <description>Change in BSA from baseline to week 3, 8, 16 and follow up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dermatological Life Quality Index, DLQI</measure>
    <time_frame>16 weeks</time_frame>
    <description>Change in DLQI from baseline to week 3, 8, 16 and follow up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PASI 75</measure>
    <time_frame>week 3 and 8</time_frame>
    <description>Change in PASI 75 from baseline to week 3 and 8 and follow up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PGA</measure>
    <time_frame>week 3 and 8</time_frame>
    <description>Change in PGA from baseline to week 3 and 8 and follow up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>ongoing</time_frame>
    <description>Ongoing safety profile over the course of the study (treatment phase and follow up)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Patient Benefit Index, PBI</measure>
    <time_frame>week 16</time_frame>
    <description>Calculation of individual benefit from therapy, assessed by patient at week 16 and in follow up</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">839</enrollment>
  <condition>Plaque Psoriasis</condition>
  <arm_group>
    <arm_group_label>LAS41008</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>up to 6 tablets/ day for 16 weeks double blind treatment period, randomized gastric resistant tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>up to 6 tablets/ day for 16 weeks randomized, double blind gastric resistant tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LASW1835</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>double blind, randomized gastric resistant tablet up to 6 tablets/ day for 16 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LAS41008</intervention_name>
    <description>gastric resistant tablet, weekly up-titration up to maximal tolerated dosage</description>
    <arm_group_label>LAS41008</arm_group_label>
    <other_name>Verum</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LASW1835</intervention_name>
    <description>gastric resistant tablet, weekly up-titration up to maximal tolerated dosage</description>
    <arm_group_label>LASW1835</arm_group_label>
    <other_name>Fumaderm initial/ Fumaderm</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>gastric resistant tablet, weekly up-titration up to maximal tolerated dosage</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed and personally dated written informed consent&#xD;
&#xD;
          2. Male / female&#xD;
&#xD;
          3. Aged 18 years or older&#xD;
&#xD;
          4. With a diagnosis of chronic plaque psoriasis for at least 12 months before enrollment&#xD;
             in the study&#xD;
&#xD;
          5. With the severity of psoriasis defined as moderate to severe, as reflected in meeting&#xD;
             all the following criteria:&#xD;
&#xD;
               -  PASI &gt; 10&#xD;
&#xD;
               -  BSA (body surface area) &gt; 10 %&#xD;
&#xD;
               -  PGA moderate to severe&#xD;
&#xD;
          6. With general good health, or a stable medical condition not considered likely to&#xD;
             interfere with the conduct of the clinical study, as determined by the investigator&#xD;
             based upon results of medical history, laboratory results and physical examination&#xD;
&#xD;
          7. Prior therapy with systemic drugs for psoriasis or naïve to systemic treatment but&#xD;
             identified as a candidate for systemic treatment.&#xD;
&#xD;
          8. With a complete record of at least 12 months of other previous topical and systemic&#xD;
             treatments, if any&#xD;
&#xD;
          9. Adhering to the following wash-out periods Topical treatment Wash-out Period&#xD;
             Corticosteroids Vitamin A analogues Vitamin D analogues Anthracene derivatives Tar&#xD;
             Salicylic acid preparations 2 weeks Systemic treatment Biologics with antipsoriatic&#xD;
             activity 3 months Conventional systemic antipsoriatic drugs and phototherapy 1 month&#xD;
             Immunosuppressive medication (if not covered by any of the above treatments)&#xD;
             Cytostatics 6 months Medications with known harmful influences on the kidneys 5 x&#xD;
             halftime&#xD;
&#xD;
         10. For females of child-bearing potential: a negative serum pregnancy test at screening&#xD;
             and willing to use highly effective methods of birth control during the study period&#xD;
             and for 60 days after the last dose of investigational product. Additionally they must&#xD;
             agree to have pregnancy tests while on study medication. Highly effective methods of&#xD;
             birth control are defined as those which result in a low failure rate (i.e. less than&#xD;
             1% per year) when used consistently and correctly, such as implants, injectables,&#xD;
             combined oral contraceptives, some IUDs, sexual abstinence or vasectomized partner.&#xD;
             Female patients will be considered to be of childbearing potential unless surgically&#xD;
             sterilized by hysterectomy or bilateral tubal ligation, or post-menopausal for at&#xD;
             least two years.&#xD;
&#xD;
         11. Males (including those who have had vasectomy) must agree to use barrier contraception&#xD;
             while on study medication&#xD;
&#xD;
         12. Willing to keep sun exposure reasonably constant and not to use tanning booths or&#xD;
             other UV light sources for the duration of the trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. For females: pregnant or lactating&#xD;
&#xD;
          2. With a diagnosis of guttate, erythrodermic or pustular psoriasis&#xD;
&#xD;
          3. With a hematological abnormality as follows: platelet count &lt; 100,000/mm3, WBC count &lt;&#xD;
             3,000 cells/ mm3, lymphocyte count &lt; 1.000/µl, hemoglobin, hematocrit, or red blood&#xD;
             cell count outside 30 % of the upper or lower limits of normal for the lab&#xD;
&#xD;
          4. With a history of malignancies except for non melanoma skin cancer&#xD;
&#xD;
          5. Suffering from significant gastrointestinal problems (ulcers, diarrhea, etc.)&#xD;
&#xD;
          6. Known to have significant renal impairment&#xD;
&#xD;
          7. Are detected to have abnormal liver enzymes &gt;2x the upper limit of the normal range&#xD;
&#xD;
          8. With active infectious disease&#xD;
&#xD;
          9. On systemic therapy with drugs that may interfere with the investigational products&#xD;
             taken within the defined wash-out period&#xD;
&#xD;
         10. With a history of alcohol or drug abuse&#xD;
&#xD;
         11. Known HIV-positive status or suffering from any other immunosuppressive disease&#xD;
&#xD;
         12. Known to be hypersensitive to ingredients of the investigational products&#xD;
&#xD;
         13. Previous enrolled in this study or participating in any other drug investigational&#xD;
             trial within the 30 days (or five half-lives whichever is longer) prior to enrolment.&#xD;
&#xD;
         14. Not willing to give consent for transmission of personal &quot;pseudonymised&quot; data&#xD;
&#xD;
         15. Unable to comply with the requirements of the study or who in the opinion of the&#xD;
             investigator should not participate in the study&#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>Ulrich Mrowietz, MD, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Medical Center, Schleswig-Holstein, Department of Dermatology, Schittenhelmstr. 7, 24105 Kiel, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Investigatives site names will not be disclosed to avoid competitive information. Specify at least one site as follows: Almirall Investigative Site</name>
      <address>
        <city>Various</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigatives site names will not be disclosed to avoid competitive information. Specify at least one site as follows: Almirall Investigative Site</name>
      <address>
        <city>Various</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigatives site names will not be disclosed to avoid competitive information. Specify at least one site as follows: Almirall Investigative Site</name>
      <address>
        <city>Various</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigatives site names will not be disclosed to avoid competitive information. Specify at least one site as follows:Almirall Investigative Site #</name>
      <address>
        <city>Various</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Germany</country>
    <country>Netherlands</country>
    <country>Poland</country>
  </location_countries>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>November 12, 2012</study_first_submitted>
  <study_first_submitted_qc>November 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 15, 2012</study_first_posted>
  <last_update_submitted>December 1, 2015</last_update_submitted>
  <last_update_submitted_qc>December 1, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 2, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>psoriasis, systemic treatment</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>Dimethyl Fumarate</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01726933
org study id: M41008-1102
secondary id: 2012-000055-13
nct id: NCT01726933
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The aim of the study is to evaluate the efficacy and safety of LAS41008 in comparison to
      active control and placebo in patients with moderate to severe chronic plaque psoriasis
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: PASI 75
time frame: 16 weeks
description: Reduction of PASI by 75% from baseline to week 16
measure: Physician Global Assessment, PGA
time frame: 16 weeks
description: Change in PGA from baseline to week 16
measure: Body Surface Area, BSA
time frame: 16 weeks
description: Change in BSA from baseline to week 3, 8, 16 and follow up
measure: Dermatological Life Quality Index, DLQI
time frame: 16 weeks
description: Change in DLQI from baseline to week 3, 8, 16 and follow up
measure: PASI 75
time frame: week 3 and 8
description: Change in PASI 75 from baseline to week 3 and 8 and follow up
measure: PGA
time frame: week 3 and 8
description: Change in PGA from baseline to week 3 and 8 and follow up
measure: Adverse events
time frame: ongoing
description: Ongoing safety profile over the course of the study (treatment phase and follow up)
measure: Patient Benefit Index, PBI
time frame: week 16
description: Calculation of individual benefit from therapy, assessed by patient at week 16 and in follow up
arm group label: LAS41008
arm group type: Experimental
description: up to 6 tablets/ day for 16 weeks double blind treatment period, randomized gastric resistant tablet
arm group label: Placebo
arm group type: Placebo Comparator
description: up to 6 tablets/ day for 16 weeks randomized, double blind gastric resistant tablet
arm group label: LASW1835
arm group type: Active Comparator
description: double blind, randomized gastric resistant tablet up to 6 tablets/ day for 16 weeks
intervention type: Drug
intervention name: LAS41008
description: gastric resistant tablet, weekly up-titration up to maximal tolerated dosage
arm group label: LAS41008
other name: Verum
intervention type: Drug
intervention name: LASW1835
description: gastric resistant tablet, weekly up-titration up to maximal tolerated dosage
arm group label: LASW1835
other name: Fumaderm initial/ Fumaderm
intervention type: Drug
intervention name: Placebo
description: gastric resistant tablet, weekly up-titration up to maximal tolerated dosage
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ulrich Mrowietz, MD, Prof
role: Principal Investigator
affiliation: University Medical Center, Schleswig-Holstein, Department of Dermatology, Schittenhelmstr. 7, 24105 Kiel, Germany
facility: 
facility: 
facility: 
facility: 
country: Austria
country: Germany
country: Netherlands
country: Poland
responsible party type: Sponsor
mesh term: Psoriasis
mesh term: Dimethyl Fumarate