<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/NCT02209753</url>
  </required_header>
  <id_info>
    <org_study_id>1175.10</org_study_id>
    <nct_id>NCT02209753</nct_id>
  </id_info>
  <brief_title>BIRB 796 BS Versus Placebo in Patients With Moderate to Severs Plaque-type Psoriasis</brief_title>
  <official_title>Phase II, Randomized, Double-blind, Placebo Controlled, Multi-center, Four Week Trial of BIRB 796 BS 5, 10, 20 and 30 mg Oral Tablets Versus Placebo Administered BID in Patients With Moderate to Severe Plaque-type Psoriasis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      The clinical objective of this study was to determine the effect of BIRB 796 BS on&#xD;
      pharmacodynamic markers of psoriasis as a measure of efficacy, to determine the population&#xD;
      pharmacokinetics of BIRB 796 BS and to determine the safety of BIRB 796 BS over 4 weeks of&#xD;
      treatment in patients with moderate to severe plaque-type psoriasis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2001</start_date>
  <primary_completion_date type="Actual">September 2002</primary_completion_date>
  <phase>Phase 2</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</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline for the total Psoriasis Area and Severity Index (PASI) score</measure>
    <time_frame>after 4 weeks of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent change from baseline for pathological thickness</measure>
    <time_frame>after 4 weeks of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of K16 negative assessments</measure>
    <time_frame>at week 4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 120 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically significant effects on laboratory values</measure>
    <time_frame>up to 36 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with abnormal findings in electrocardiogram</measure>
    <time_frame>up to day 29</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically significant changes in vital signs</measure>
    <time_frame>up to day 36</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Absolute change from baseline in the number of epidermal T cells</measure>
    <time_frame>after 4 weeks of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute change from baseline in the number of dermal T cells</measure>
    <time_frame>after 4 weeks of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relative (%) change from baseline in the number of dermal T cells</measure>
    <time_frame>after 4 weeks of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relative (%) change from baseline in the number of epidermal T cells</measure>
    <time_frame>after 4 weeks of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PASI 50 responder</measure>
    <time_frame>after 4 weeks of treatment</time_frame>
    <description>reduction of total PASI score by 50% or more</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of target lesions on a 5-point numeric scale</measure>
    <time_frame>day 1 and 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) gene expression for cytokines</measure>
    <time_frame>days 1, 8 and 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of serum immunological markers of disease activity</measure>
    <time_frame>day 1 and 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in score of total body lesion</measure>
    <time_frame>day 1 and 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of inducible nitric oxide synthase (iNOS)</measure>
    <time_frame>day 1 and 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PASI 75 responder</measure>
    <time_frame>after 4 weeks of treatment</time_frame>
    <description>reduction of total PASI by 75%</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Histopathological global assessment on a 4-point scale</measure>
    <time_frame>after 4 weeks of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Keratin K16 improvement score</measure>
    <time_frame>after 4 weeks of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>20% reduction responder variable for pathological thickness</measure>
    <time_frame>after 4 weeks of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>20% reduction responder variable for iNOS</measure>
    <time_frame>after 4 weeks of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of K16 mRNA</measure>
    <time_frame>day 1 and 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of COX-2 mRNA</measure>
    <time_frame>day 1 and 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>20% reduction responder variable for K16</measure>
    <time_frame>after 4 weeks of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>20% reduction responder variable for interleukin 8 mRNA</measure>
    <time_frame>after 4 weeks of treatment</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">182</enrollment>
  <condition>Psoriasis</condition>
  <arm_group>
    <arm_group_label>BIRB 796 BS, low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BIRB 796 BS, medium dose 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BIRB 796 BS, medium dose 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BIRB 796 BS, high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIRB 796 BS, low dose</intervention_name>
    <arm_group_label>BIRB 796 BS, low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIRB 796 BS, medium dose 1</intervention_name>
    <arm_group_label>BIRB 796 BS, medium dose 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIRB 796 BS, medium dose 2</intervention_name>
    <arm_group_label>BIRB 796 BS, medium dose 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIRB 796 BS, high dose</intervention_name>
    <arm_group_label>BIRB 796 BS, high dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with stable moderate to severe plaque-type psoriasis involving ≥5% body&#xD;
             surface area&#xD;
&#xD;
          -  History of plaque psoriasis for a minimum of 6 months prior to screening&#xD;
&#xD;
          -  Age 18 - 75&#xD;
&#xD;
          -  Males or females, females must be of non-childbearing potential (6 months&#xD;
             post-menopausal, surgically sterilized) or using an approved form of birth control&#xD;
             (oral contraceptives, Norplant®, Depo-Provera®, intrauterine device (IUD),&#xD;
             double-barrier) and have a negative serum pregnancy test upon screening (Visit 1) and&#xD;
             a negative urine test prior to randomization (Visit 2) into the trial&#xD;
&#xD;
          -  Give informed consent and sign an approved consent form prior to any study procedures,&#xD;
             including washout of prohibited medications&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Primary guttate, erythrodermic, or pustular psoriasis&#xD;
&#xD;
          -  Psoriasis which has failed to improve significantly with systemic treatments such as&#xD;
             cyclosporine or methotrexate. Patients resistant to one, but have had a documented&#xD;
             response to another may be included with approval of the medical monitor. Treatment&#xD;
             failure will not include failure to improve if a full course of treatment was unable&#xD;
             to be completed due to adverse events, intolerance of the treatment or administrative&#xD;
             reasons&#xD;
&#xD;
          -  Patients who have experienced treatment failure with a TNF-blocking agent. Treatment&#xD;
             failure is defined as not achieving at least a 40% reduction in PASI score or having&#xD;
             the TNF-blocking agent discontinued due to lack of efficacy&#xD;
&#xD;
          -  Patients unable to wash out of all current psoriasis treatments (systemic, topical and&#xD;
             phototherapy) except emollients and shampoos prior to beginning trial medication&#xD;
&#xD;
          -  Patients taking the following medications known to elevate liver enzymes who have not&#xD;
             been taking these medications at a stable dose for at least 1 month (3 months for&#xD;
             diclofenac) without changes to liver functions tests (LFTs) prior to randomization&#xD;
             (Visit 2): estrogens, oral contraceptives, selective serotonin reuptake inhibitors&#xD;
             (SSRIs), nonsteroidal anti-inflammatory drugs (NSAIDs), acetominophen ≤3 g/day,&#xD;
             aspirin, vitamin supplements (at recommended daily allowance doses). Patients taking&#xD;
             doses of acetaminophen greater than three grams per day are excluded. Any other&#xD;
             medication known to elevate hepatic enzymes not listed above is excluded&#xD;
&#xD;
          -  Patients using any of the medications listed in the protocol, without the appropriate&#xD;
             washout period&#xD;
&#xD;
          -  Patients with clinically significant abnormal baseline hematology, blood chemistry or&#xD;
             urinalysis if the abnormality defines a disease listed as an exclusion criterion. All&#xD;
             patients with a serum glutamate oxaloacetate transaminase, serum glutamate pyruvate&#xD;
             transaminase , alkaline phosphatase greater than 1.5 x upper limit of normal (ULN) or&#xD;
             total bilirubin greater than 1.0 x ULN will be excluded regardless of the clinical&#xD;
             condition. Patients with serum creatinine, white blood cell (WBC) count, amylase,&#xD;
             lipase, prothrombin time (PT), partial thromboplastin time (PTT), D-dimer, fibrin&#xD;
             degradation product (FDP) greater than 1.5 x ULN, or blood smear poikilocytes or&#xD;
             schistocytes greater than 1.0 x ULN will also be excluded. Patients with&#xD;
             hemoglobinuria or proteinuria greater than 1+ will be excluded. Hemoglobinuria must be&#xD;
             confirmed as hematuria with finding of red blood cell (RBC) on microscopic&#xD;
             examination. Hematuria in a menstruating female will not require exclusion but must be&#xD;
             repeated after menses has cleared prior to entry. Repeat laboratory testing is allowed&#xD;
             once at screening prior to excluding the patient, to avoid excluding patients with&#xD;
             transient or erroneous abnormal laboratory values&#xD;
&#xD;
          -  Any clinically significant psychiatric illness which may interfere with the patient's&#xD;
             participation in the trial or ability to interpret the trial results&#xD;
&#xD;
          -  History of cardiovascular, renal, neurologic, liver, immunologic or endocrine&#xD;
             dysfunction if they are clinically significant. A clinically significant disease is&#xD;
             defined as one which in the opinion of the investigator may either put the patient at&#xD;
             risk because of participation in the study or a disease which may influence the&#xD;
             results of the study or the patient's ability to participate in the study&#xD;
&#xD;
          -  Patients with any history of heart failure, patients with a recent history (i.e., 1&#xD;
             year or less) of myocardial infarction or patients with any arrhythmia requiring drug&#xD;
             therapy&#xD;
&#xD;
          -  Any ECG value outside of the reference range of clinical relevance including, but not&#xD;
             limited to, QTcB &gt;480 ms, PR interval &gt;240 ms, QRS interval &gt;110 ms&#xD;
&#xD;
          -  History of malignancy in the past 5 years except treated cutaneous squamous cell or&#xD;
             basal cell carcinoma&#xD;
&#xD;
          -  Any active immunodeficiency or active infection, or any serious infection (requiring&#xD;
             hospitalization or IV/intramuscular antibiotics) in the past 3 months prior to&#xD;
             screening. Patients testing positive to human immunodeficiency virus (HIV), hepatitis&#xD;
             B or hepatitis C will be excluded&#xD;
&#xD;
          -  History of prior tuberculosis infection or active tuberculosis, patients must have a&#xD;
             negative skin test or chest x-ray within the past 6 months prior to screening (Visit&#xD;
             1)&#xD;
&#xD;
          -  History of drug or alcohol abuse within the past 2 years, active drug or alcohol&#xD;
             abuse, or patients who consume more than three alcoholic drinks per day&#xD;
&#xD;
          -  Patients who have taken an investigational drug within one month (30 days) or six half&#xD;
             lives (whichever is greater) prior to screening (Visit 1). Patients who have been&#xD;
             treated with any investigational antibody or other biological agent within the past 3&#xD;
             months are excluded&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 5, 2014</study_first_submitted>
  <study_first_submitted_qc>August 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 6, 2014</study_first_posted>
  <last_update_submitted>August 5, 2014</last_update_submitted>
  <last_update_submitted_qc>August 5, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 6, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psoriasis</mesh_term>
  </condition_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/NCT02209753
org study id: 1175.10
nct id: NCT02209753
lead sponsor: 
The clinical objective of this study was to determine the effect of BIRB 796 BS on
      pharmacodynamic markers of psoriasis as a measure of efficacy, to determine the population
      pharmacokinetics of BIRB 796 BS and to determine the safety of BIRB 796 BS over 4 weeks of
      treatment in patients with moderate to severe plaque-type psoriasis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Change from baseline for the total Psoriasis Area and Severity Index (PASI) score
time frame: after 4 weeks of treatment
measure: Percent change from baseline for pathological thickness
time frame: after 4 weeks of treatment
measure: Percentage of K16 negative assessments
time frame: at week 4
measure: Number of patients with adverse events
time frame: up to 120 days
measure: Number of patients with clinically significant effects on laboratory values
time frame: up to 36 days
measure: Number of patients with abnormal findings in electrocardiogram
time frame: up to day 29
measure: Number of patients with clinically significant changes in vital signs
time frame: up to day 36
measure: Absolute change from baseline in the number of epidermal T cells
time frame: after 4 weeks of treatment
measure: Absolute change from baseline in the number of dermal T cells
time frame: after 4 weeks of treatment
measure: Relative (%) change from baseline in the number of dermal T cells
time frame: after 4 weeks of treatment
measure: Relative (%) change from baseline in the number of epidermal T cells
time frame: after 4 weeks of treatment
measure: PASI 50 responder
time frame: after 4 weeks of treatment
description: reduction of total PASI score by 50% or more
measure: Assessment of target lesions on a 5-point numeric scale
time frame: day 1 and 29
measure: Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) gene expression for cytokines
time frame: days 1, 8 and 29
measure: Reduction of serum immunological markers of disease activity
time frame: day 1 and 29
measure: Change in score of total body lesion
time frame: day 1 and 29
measure: Reduction of inducible nitric oxide synthase (iNOS)
time frame: day 1 and 29
measure: PASI 75 responder
time frame: after 4 weeks of treatment
description: reduction of total PASI by 75%
measure: Histopathological global assessment on a 4-point scale
time frame: after 4 weeks of treatment
measure: Keratin K16 improvement score
time frame: after 4 weeks of treatment
measure: 20% reduction responder variable for pathological thickness
time frame: after 4 weeks of treatment
measure: 20% reduction responder variable for iNOS
time frame: after 4 weeks of treatment
measure: Reduction of K16 mRNA
time frame: day 1 and 29
measure: Reduction of COX-2 mRNA
time frame: day 1 and 29
measure: 20% reduction responder variable for K16
time frame: after 4 weeks of treatment
measure: 20% reduction responder variable for interleukin 8 mRNA
time frame: after 4 weeks of treatment
arm group label: BIRB 796 BS, low dose
arm group type: Experimental
arm group label: BIRB 796 BS, medium dose 1
arm group type: Experimental
arm group label: BIRB 796 BS, medium dose 2
arm group type: Experimental
arm group label: BIRB 796 BS, high dose
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BIRB 796 BS, low dose
arm group label: BIRB 796 BS, low dose
intervention type: Drug
intervention name: BIRB 796 BS, medium dose 1
arm group label: BIRB 796 BS, medium dose 1
intervention type: Drug
intervention name: BIRB 796 BS, medium dose 2
arm group label: BIRB 796 BS, medium dose 2
intervention type: Drug
intervention name: BIRB 796 BS, high dose
arm group label: BIRB 796 BS, high dose
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Psoriasis