<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/NCT02215824</url>
  </required_header>
  <id_info>
    <org_study_id>1181.1</org_study_id>
    <nct_id>NCT02215824</nct_id>
  </id_info>
  <brief_title>Investigation of Safety, Pharmacokinetics and Pharmacodynamics of Different Doses of BIWH 3 in Patients With Chronic Critical Limb Ischaemia</brief_title>
  <acronym>COINART-1</acronym>
  <official_title>A Randomised, Double-blind, Placebo-controlled, Dose Escalation Study to Investigate Safety, Pharmacokinetics and Pharmacodynamics of Different Doses (0.2, 0.6, 2.0, 6.0, and 20.0 μg/hr) of BIWH 3 Administered for 6 Hours in Patients With Chronic Critical Limb Ischaemia (CLI, Fontaine Class III or IV). COINART-1 Trial (First COllateral INto ARTery Trial)</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 primary aim of this trial was to investigate the safety of a 6 hour intraarterial&#xD;
      infusion of BIWH 3 (pyro-Glu-rhMCP-1) in patients with severe peripheral arterial occlusive&#xD;
      disease (PAOD) and chronic Critical Limb Ischaemia (Fontaine class III or IV).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date>October 2002</start_date>
  <primary_completion_date type="Actual">October 2003</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</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 180 days after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically relevant changes in vital signs (heart rate, blood pressure, body temperature)</measure>
    <time_frame>baseline, up to 180 days after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically relevant changes in laboratory evaluations</measure>
    <time_frame>baseline, up to 180 days after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically relevant changes in 12- lead electrocardiogram (ECG)</measure>
    <time_frame>baseline, up to 180 days after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically relevant changes in markers of inflammation</measure>
    <time_frame>baseline, up to 180 days after drug administration</time_frame>
    <description>measured by C-reactive Protein (CRP) and erythrocyte sedimentation rate (ESR)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically relevant changes in ophthalmic examinations</measure>
    <time_frame>baseline, up to 180 days after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with changes from baseline in progression of atherosclerosis</measure>
    <time_frame>day 180</time_frame>
    <description>measured by carotid duplex imaging</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with changes in local disease defined by degree of stenosis</measure>
    <time_frame>up to 6 months post treatment</time_frame>
    <description>assessed by magnetic resonance angiography</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with changes from baseline in result of cancer screening</measure>
    <time_frame>day 180</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients developing an antibody response to BIWH 3</measure>
    <time_frame>baseline, up to 180 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in transcutaneous oxygen pressure (tcPO2)</measure>
    <time_frame>baseline, up to 180 days after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in lower extremity magnetic resonance angiography (MRA)</measure>
    <time_frame>baseline, up to 180 days after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in ankle brachial or toe brachial index</measure>
    <time_frame>baseline, up to 180 days after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurence of amputations</measure>
    <time_frame>up to 180 days after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression of ulcer healing</measure>
    <time_frame>up to 180 days after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline on visual analogue scale assessment of pain at rest</measure>
    <time_frame>up to 180 days after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BIWH 3 plasma concentration</measure>
    <time_frame>up to 180 days after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Mac-1 positive staining monocytes</measure>
    <time_frame>up to 180 days after drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Peripheral Arterial Disease</condition>
  <arm_group>
    <arm_group_label>BIWH 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>in escalating doses</description>
  </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>BIWH 3</intervention_name>
    <arm_group_label>BIWH 3</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:&#xD;
&#xD;
          -  Patient must have severe PAOD with Chronic Critical Limb Ischaemia, Fontaine class III&#xD;
             (ischaemic pain at rest) or IV (tissue ulceration or gangrene) due to atherosclerotic&#xD;
             disease&#xD;
&#xD;
          -  Patient must be &gt;= 18 years of age&#xD;
&#xD;
          -  Patient must give written informed consent&#xD;
&#xD;
          -  Patient must have a life expectancy of at least six months&#xD;
&#xD;
        Exclusion:&#xD;
&#xD;
          -  Transient ischaemic attack (TIA), cerebral vascular accident (CVA), myocardial&#xD;
             infarction (MI) or episode of unstable angina within the past two months&#xD;
&#xD;
          -  Ophthalmologic conditions: moderate to severe nonproliferative retinopathy,&#xD;
             proliferative retinopathy, age related maculopathy with choroidal neovascularisation,&#xD;
             macular edema, intraocular surgery within the previous 6 months, retinal vein&#xD;
             occlusion&#xD;
&#xD;
          -  Presence of a clinically significant disease which in the opinion of the investigator&#xD;
             may either put the patient at risk because of participation in the study or a disease&#xD;
             which may influence the result of the study or the patient's ability to participate in&#xD;
             the study&#xD;
&#xD;
          -  ECG results outside of the reference range of clinical relevance including, but not&#xD;
             limited to QTcB &gt; 480 msec, PR interval &gt; 240 msec, QRS interval &gt; 140 msec&#xD;
&#xD;
          -  History of malignant disease, or a positive result on any of the required cancer&#xD;
             screening tests, unless a definitive subsequent evaluation for cancer is determined to&#xD;
             be negative&#xD;
&#xD;
          -  Patients at increased risk of colorectal cancer, including any of the following (1)&#xD;
             colorectal cancer pr polyps in a first-degree relative younger than 60 or in two&#xD;
             first-degree relatives of any age, (2) family history of familial adenomatous&#xD;
             polyposis or hereditary non-polyposis colon cancer, (3) history of adenomatous polyps,&#xD;
             or (4) history of chronic inflammatory bowel disease (chronic ulcerative colitis or&#xD;
             Crohn's disease)&#xD;
&#xD;
          -  Abnormalities greater than two times the upper limit of normal in any of the following&#xD;
             laboratory values at Visit 1: alanine-aminotransferase (ALT),&#xD;
             aspartate-aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline&#xD;
             phosphatase or lactic dehydrogenase (LDH); abnormalities greater than 1.5 times the&#xD;
             upper limit of normal of total bilirubin or white blood cell count&#xD;
&#xD;
          -  Any concurrent infectious disease requiring treatment&#xD;
&#xD;
          -  Severe renal insufficiency (estimated creatinine clearance &lt; 30 mL/min)&#xD;
&#xD;
          -  Duffy antigen negative blood type with co-existing moderate to severe renal&#xD;
             insufficiency (estimated creatinine clearance &lt; 80 mL/min), to avoid potential risk of&#xD;
             significant increase of monocyte chemoattractant protein-1 (MCP-1) levels&#xD;
&#xD;
          -  Known glomerulonephritis, even if creatinine clearance is apparently normal&#xD;
&#xD;
          -  Thrombocytopenia, i.e. platelet count &lt;100,000 cells/μl at Visit 1&#xD;
&#xD;
          -  History of drug or alcohol abuse within the past 2 two years or active drug or alcohol&#xD;
             abuse, present alcohol intake more than three drinks per day&#xD;
&#xD;
          -  Inability to comply with the protocol&#xD;
&#xD;
          -  Treatment with an investigational drug within 30 days or 5 half-lives, whichever is&#xD;
             greater before Visit 2&#xD;
&#xD;
          -  Use of cilostazol if cilostazol therapy was started within 2 months prior to trial&#xD;
             enrollment, or planned initiation of cilostazol therapy during the trial period.&#xD;
             Patients who have been on cilostazol for &gt; 2 months prior to enrollment may be&#xD;
             enrolled&#xD;
&#xD;
          -  Inability to discontinue the intake of coumadin until after completion of the&#xD;
             treatment period. Patients who were on coumadin must have an international normalised&#xD;
             ratio (INR) &lt; 1.8 at Visit 2&#xD;
&#xD;
          -  Previous enrollment in this trial&#xD;
&#xD;
          -  Hypersensitivity or allergy to heparin, conventional angiographic contrast dye, or&#xD;
             magnetic resonance angiography (MRA) contrast&#xD;
&#xD;
          -  Inability to undergo MRA (e.g. heart pacemaker, artificial heart valve, implanted&#xD;
             neurostimulator, intrauterine device (IUD), metallic ear implant, implanted port for&#xD;
             delivering insulin, or other foreign or implanted or metallic objects such as bullet&#xD;
             fragments, metal plates, pins, screws or staples, joint replacement, or penile&#xD;
             implant)&#xD;
&#xD;
          -  Know HIV-infection&#xD;
&#xD;
          -  Unwillingness to take blood products&#xD;
&#xD;
          -  Pregnancy (to be excluded by serum and urine beta-human chorionic gonadotropin-test in&#xD;
             women of childbearing potential) or breast feeding&#xD;
&#xD;
          -  Female of childbearing potential (not 12 months post-menopausal or surgically&#xD;
             sterilized) not using one of the following methods of birth control: hormonal&#xD;
             contraceptives, oral or injectable/implantable&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</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 12, 2014</study_first_submitted>
  <study_first_submitted_qc>August 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>August 21, 2014</last_update_submitted>
  <last_update_submitted_qc>August 21, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 22, 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>Peripheral Arterial Disease</mesh_term>
    <mesh_term>Peripheral Vascular Diseases</mesh_term>
    <mesh_term>Chronic Limb-Threatening Ischemia</mesh_term>
    <mesh_term>Ischemia</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/NCT02215824
org study id: 1181.1
nct id: NCT02215824
lead sponsor: 
The primary aim of this trial was to investigate the safety of a 6 hour intraarterial
      infusion of BIWH 3 (pyro-Glu-rhMCP-1) in patients with severe peripheral arterial occlusive
      disease (PAOD) and chronic Critical Limb Ischaemia (Fontaine class III or IV).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Number of patients with adverse events
time frame: up to 180 days after drug administration
measure: Number of patients with clinically relevant changes in vital signs (heart rate, blood pressure, body temperature)
time frame: baseline, up to 180 days after drug administration
measure: Number of patients with clinically relevant changes in laboratory evaluations
time frame: baseline, up to 180 days after drug administration
measure: Number of patients with clinically relevant changes in 12- lead electrocardiogram (ECG)
time frame: baseline, up to 180 days after drug administration
measure: Number of patients with clinically relevant changes in markers of inflammation
time frame: baseline, up to 180 days after drug administration
description: measured by C-reactive Protein (CRP) and erythrocyte sedimentation rate (ESR)
measure: Number of patients with clinically relevant changes in ophthalmic examinations
time frame: baseline, up to 180 days after drug administration
measure: Number of patients with changes from baseline in progression of atherosclerosis
time frame: day 180
description: measured by carotid duplex imaging
measure: Number of patients with changes in local disease defined by degree of stenosis
time frame: up to 6 months post treatment
description: assessed by magnetic resonance angiography
measure: Number of patients with changes from baseline in result of cancer screening
time frame: day 180
measure: Number of patients developing an antibody response to BIWH 3
time frame: baseline, up to 180 days
measure: Changes in transcutaneous oxygen pressure (tcPO2)
time frame: baseline, up to 180 days after drug administration
measure: Changes in lower extremity magnetic resonance angiography (MRA)
time frame: baseline, up to 180 days after drug administration
measure: Changes in ankle brachial or toe brachial index
time frame: baseline, up to 180 days after drug administration
measure: Occurence of amputations
time frame: up to 180 days after drug administration
measure: Progression of ulcer healing
time frame: up to 180 days after drug administration
measure: Changes from baseline on visual analogue scale assessment of pain at rest
time frame: up to 180 days after drug administration
measure: BIWH 3 plasma concentration
time frame: up to 180 days after drug administration
measure: Occurrence of Mac-1 positive staining monocytes
time frame: up to 180 days after drug administration
arm group label: BIWH 3
arm group type: Experimental
description: in escalating doses
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BIWH 3
arm group label: BIWH 3
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Peripheral Arterial Disease
mesh term: Peripheral Vascular Diseases
mesh term: Chronic Limb-Threatening Ischemia
mesh term: Ischemia