<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/NCT01702740</url>
  </required_header>
  <id_info>
    <org_study_id>CR013000</org_study_id>
    <secondary_id>C0136T03</secondary_id>
    <secondary_id>2006-002432-25</secondary_id>
    <nct_id>NCT01702740</nct_id>
  </id_info>
  <brief_title>A Study of the Safety and Pharmacokinetics of CNTO 136 in Patients With Cutaneous Lupus Erythematosus and Systemic Lupus Erythematosus</brief_title>
  <official_title>A Phase 1, Double-blind, Placebo-controlled, Multiple Intravenous, Ascending-Dose Study of CNTO 136 to Evaluate Safety and Pharmacokinetics in Subjects With Cutaneous Lupus Erythematosus and to Evaluate Safety and Pharmacokinetics in a Cohort of Subjects With Systemic Lupus Erythematosus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centocor Research &amp; Development, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centocor Research &amp; Development, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study was to evaluate the safety and pharmacokinetics (PK, the&#xD;
      action of a drug in the body over a period of time) of multiple intravenous (IV)&#xD;
      administrations of CNTO 136 in patients with cutaneous lupus erythematosus (CLE) and systemic&#xD;
      lupus erythematosus (SLE). The secondary goal of this study was to assess the&#xD;
      pharmacodynamics (biochemical and physiological effects of a drug and the mechanisms of&#xD;
      action), immune response, and clinical response.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In Part A of this study, patients with CLE were randomly assigned (like flipping a coin) to&#xD;
      receive multiple IV doses of CNTO 136, a human anti-IL 6 monoclonal antibody (an immune&#xD;
      protein that binds to interleukin 6) or placebo (a substance that appears identical to the&#xD;
      treatment and has no active ingredients). Patients and study personnel did not know the&#xD;
      identity of the administered treatments (double-blind study). Increasing doses were given,&#xD;
      based on safety data collected during the initial weeks of treatment. In Part B, which was&#xD;
      also double-blind, patients with SLE were randomly assigned to receive multiple IV doses of&#xD;
      the highest well-tolerated dose, as determined in Part A, of CNTO 136, or placebo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2007</start_date>
  <completion_date type="Actual">October 2009</completion_date>
  <primary_completion_date type="Actual">October 2009</primary_completion_date>
  <phase>Phase 1</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>Number of participants with adverse events</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic profile of CNTO 136</measure>
    <time_frame>Up to 22 weeks</time_frame>
    <description>Blood serum concentration over time</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Physical examinations</measure>
    <time_frame>Up to 26 weeks</time_frame>
    <description>Assessment of head, eyes, ears, nose and throat, skin and neck, lungs, heart, abdomen, extremities, general neurologic status, and oral examination</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Electrocardiograms (ECGs)</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Sitting blood pressure</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Heart rate</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Respiration rate</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Oral temperature</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Hemoglobin</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Hematocrit</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Platelets and total white blood cells (WBC)</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Albumin and total protein</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST)</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood urea nitrogen (BUN), calcium, creatinine, and total bilirubin</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Chloride, potassium, and sodium</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Bicarbonate</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Creatine kinase</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Gamma-glutamyl-transferase</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Glucose</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Lymphocytes and neutrophils</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Inorganic phosphate</measure>
    <time_frame>Up to 26 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Fasting Lipid Panel</measure>
    <time_frame>Up to 8 weeks</time_frame>
    <description>Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and triglycerides.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics evaluations</measure>
    <time_frame>Up to 22 weeks</time_frame>
    <description>Percentage change from baseline in serum and plasma biomarker data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune response</measure>
    <time_frame>Up to 22 weeks</time_frame>
    <description>The formation of antibodies to CNTO 136</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)</measure>
    <time_frame>Up to 22 weeks</time_frame>
    <description>Measurement of disease activity, scored from 0 (absent) to 70 (severe), and damage, scored from 0 (absent) to 56 (severe)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>British Isles Lupus Assessment Group (BILAG) score</measure>
    <time_frame>Up to 22 weeks</time_frame>
    <description>Measures the need for alterations or intensification of therapy. The assessing physician considers each item as to its presence in the past month, and answers 0 = not present, 1 = improving; 2 = same; 3 = worse; or 4 = new.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SELENA-SLEDAI Flare Composite</measure>
    <time_frame>Up to 22 weeks</time_frame>
    <description>Assesses the presence and severity of lupus flare. Scores range from 0 (mild) to 105 (severe).</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">49</enrollment>
  <condition>Lupus Erythematosus, Cutaneous</condition>
  <condition>Lupus Erythematosus, Systemic</condition>
  <arm_group>
    <arm_group_label>Part A, 1 mg/kg CNTO 136</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A, 4 mg/kg CNTO 136</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A, 10 mg/kg CNTO 136</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B, 10 mg/kg CNTO 136/placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>1 mg/kg CNTO 136</intervention_name>
    <description>Type=exact number, unit=mg, number=1, form=powder for solution for infusion, route=intravenous use, every 2 weeks for 6 weeks.</description>
    <arm_group_label>Part A, 1 mg/kg CNTO 136</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>4 mg/kg CNTO 136</intervention_name>
    <description>Type=exact number, unit=mg, number=4, form=powder for solution for infusion, route=intravenous use, every 2 weeks for 6 weeks.</description>
    <arm_group_label>Part A, 4 mg/kg CNTO 136</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>10 mg/kg CNTO 136</intervention_name>
    <description>Type=exact number, unit=mg, number=10, form=powder for solution for infusion, route=intravenous use, every 2 weeks for 6 weeks.</description>
    <arm_group_label>Part A, 10 mg/kg CNTO 136</arm_group_label>
    <arm_group_label>Part B, 10 mg/kg CNTO 136/placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Form=liquid for infusion, route=intravenous use, every 2 weeks for 6 weeks.</description>
    <arm_group_label>Part B, 10 mg/kg CNTO 136/placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of cutaneous lupus erythematosus (CLE, including subacute cutaneous lupus&#xD;
             erythematosus, discoid lupus erythematosus, or lupus erythematosus tumidus) or&#xD;
             systemic lupus erythematosus (SLE)&#xD;
&#xD;
               -  Had a body weight less than or equal to 100 kg&#xD;
&#xD;
               -  Patients in Part A who were taking systemic medications for CLE had to be on a&#xD;
                  stable dose for 4 weeks before the first study agent infusion&#xD;
&#xD;
               -  Patients in Part B taking systemic medications for SLE had to be on a stable dose&#xD;
                  for at least 3 months before the first study agent infusion&#xD;
&#xD;
               -  Given informed consent and willing and able to adhere to the study visit schedule&#xD;
                  and other protocol requirements; agreed to avoid alcohol intake; and took&#xD;
                  adequate measures to prevent pregnancy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Significant history of or concurrent medical condition (other than lupus)&#xD;
&#xD;
          -  Use of specific previous or concurrent medications or investigational therapies&#xD;
&#xD;
          -  Known or suspected allergy to the study agent or it constituents, having recently&#xD;
             donated blood, or having any significant laboratory test values requiring intervention&#xD;
&#xD;
          -  Patients with SLE in Part B could not have active central nervous system lupus&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Centocor Research &amp; Development, Inc., PA, USA Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Centocor Research &amp; Development, Inc.</affiliation>
  </overall_official>
  <verification_date>October 2012</verification_date>
  <study_first_submitted>July 6, 2012</study_first_submitted>
  <study_first_submitted_qc>October 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2012</study_first_posted>
  <last_update_submitted>October 5, 2012</last_update_submitted>
  <last_update_submitted_qc>October 5, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 8, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cutaneous lupus erythematosus</keyword>
  <keyword>Systemic lupus erythematosus</keyword>
  <keyword>Lupus erythematosus</keyword>
  <keyword>Human anti-IL 6 monoclonal antibody</keyword>
  <keyword>Sirukumab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lupus Erythematosus, Systemic</mesh_term>
    <mesh_term>Lupus Erythematosus, Cutaneous</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/NCT01702740
org study id: CR013000
secondary id: C0136T03
secondary id: 2006-002432-25
nct id: NCT01702740
lead sponsor: 
has dmc: No
The main purpose of this study was to evaluate the safety and pharmacokinetics (PK, the
      action of a drug in the body over a period of time) of multiple intravenous (IV)
      administrations of CNTO 136 in patients with cutaneous lupus erythematosus (CLE) and systemic
      lupus erythematosus (SLE). The secondary goal of this study was to assess the
      pharmacodynamics (biochemical and physiological effects of a drug and the mechanisms of
      action), immune response, and clinical response.
In Part A of this study, patients with CLE were randomly assigned (like flipping a coin) to
      receive multiple IV doses of CNTO 136, a human anti-IL 6 monoclonal antibody (an immune
      protein that binds to interleukin 6) or placebo (a substance that appears identical to the
      treatment and has no active ingredients). Patients and study personnel did not know the
      identity of the administered treatments (double-blind study). Increasing doses were given,
      based on safety data collected during the initial weeks of treatment. In Part B, which was
      also double-blind, patients with SLE were randomly assigned to receive multiple IV doses of
      the highest well-tolerated dose, as determined in Part A, of CNTO 136, or placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Number of participants with adverse events
time frame: Up to 26 weeks
measure: Pharmacokinetic profile of CNTO 136
time frame: Up to 22 weeks
description: Blood serum concentration over time
measure: Physical examinations
time frame: Up to 26 weeks
description: Assessment of head, eyes, ears, nose and throat, skin and neck, lungs, heart, abdomen, extremities, general neurologic status, and oral examination
measure: Electrocardiograms (ECGs)
time frame: Up to 26 weeks
measure: Sitting blood pressure
time frame: Up to 26 weeks
measure: Heart rate
time frame: Up to 26 weeks
measure: Respiration rate
time frame: Up to 26 weeks
measure: Oral temperature
time frame: Up to 26 weeks
measure: Hemoglobin
time frame: Up to 26 weeks
measure: Hematocrit
time frame: Up to 26 weeks
measure: Platelets and total white blood cells (WBC)
time frame: Up to 26 weeks
measure: Albumin and total protein
time frame: Up to 26 weeks
measure: Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST)
time frame: Up to 26 weeks
measure: Blood urea nitrogen (BUN), calcium, creatinine, and total bilirubin
time frame: Up to 26 weeks
measure: Chloride, potassium, and sodium
time frame: Up to 26 weeks
measure: Bicarbonate
time frame: Up to 26 weeks
measure: Creatine kinase
time frame: Up to 26 weeks
measure: Gamma-glutamyl-transferase
time frame: Up to 26 weeks
measure: Glucose
time frame: Up to 26 weeks
measure: Lymphocytes and neutrophils
time frame: Up to 26 weeks
measure: Inorganic phosphate
time frame: Up to 26 weeks
measure: Fasting Lipid Panel
time frame: Up to 8 weeks
description: Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and triglycerides.
measure: Pharmacodynamics evaluations
time frame: Up to 22 weeks
description: Percentage change from baseline in serum and plasma biomarker data
measure: Immune response
time frame: Up to 22 weeks
description: The formation of antibodies to CNTO 136
measure: Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)
time frame: Up to 22 weeks
description: Measurement of disease activity, scored from 0 (absent) to 70 (severe), and damage, scored from 0 (absent) to 56 (severe)
measure: British Isles Lupus Assessment Group (BILAG) score
time frame: Up to 22 weeks
description: Measures the need for alterations or intensification of therapy. The assessing physician considers each item as to its presence in the past month, and answers 0 = not present, 1 = improving; 2 = same; 3 = worse; or 4 = new.
measure: SELENA-SLEDAI Flare Composite
time frame: Up to 22 weeks
description: Assesses the presence and severity of lupus flare. Scores range from 0 (mild) to 105 (severe).
arm group label: Part A, 1 mg/kg CNTO 136
arm group type: Experimental
arm group label: Part A, 4 mg/kg CNTO 136
arm group type: Experimental
arm group label: Part A, 10 mg/kg CNTO 136
arm group type: Experimental
arm group label: Part B, 10 mg/kg CNTO 136/placebo
arm group type: Experimental
intervention type: Drug
intervention name: 1 mg/kg CNTO 136
description: Type=exact number, unit=mg, number=1, form=powder for solution for infusion, route=intravenous use, every 2 weeks for 6 weeks.
arm group label: Part A, 1 mg/kg CNTO 136
intervention type: Drug
intervention name: 4 mg/kg CNTO 136
description: Type=exact number, unit=mg, number=4, form=powder for solution for infusion, route=intravenous use, every 2 weeks for 6 weeks.
arm group label: Part A, 4 mg/kg CNTO 136
intervention type: Drug
intervention name: 10 mg/kg CNTO 136
description: Type=exact number, unit=mg, number=10, form=powder for solution for infusion, route=intravenous use, every 2 weeks for 6 weeks.
arm group label: Part A, 10 mg/kg CNTO 136
arm group label: Part B, 10 mg/kg CNTO 136/placebo
intervention type: Drug
intervention name: Placebo
description: Form=liquid for infusion, route=intravenous use, every 2 weeks for 6 weeks.
arm group label: Part B, 10 mg/kg CNTO 136/placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Centocor Research & Development, Inc., PA, USA Clinical Trial
role: Study Director
affiliation: Centocor Research & Development, Inc.
responsible party type: Sponsor
mesh term: Lupus Erythematosus, Systemic
mesh term: Lupus Erythematosus, Cutaneous