<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/NCT01669421</url>
  </required_header>
  <id_info>
    <org_study_id>20100844</org_study_id>
    <nct_id>NCT01669421</nct_id>
  </id_info>
  <brief_title>Effect of Double Dose of Alpha 1-antitrypsin Augmentation Therapy on Lung Inflammation.</brief_title>
  <official_title>Effect of a Higher Dose of Alpha-1 Antitrypsin Augmentation Therapy on Lung Inflammation in Subjects With Alpha-1 Antitrypsin Deficiency.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Michael Campos, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>CSL Behring</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Miami</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The current treatment of individuals with alpha-1 antitrypsin deficiency (AATD) who develop&#xD;
      lung disease (COPD) is the administration of intravenous purified alpha-1 antitrypsin&#xD;
      (augmentation therapy) at a fixed dose of 60 mg/kg per week. This dose aims at increasing the&#xD;
      deficient AAT serum levels just above a predetermined &quot;safety threshold&quot; of 11 uM. However,&#xD;
      normal levels of AAT are between 25-50 uM.&#xD;
&#xD;
      AAT has shown not only to inhibit lung proteases such as neutrophil elastase, but also to&#xD;
      modulate inflammation. Given that many subjects with AATD who receive augmentation therapy&#xD;
      still have significant lung disease and inflammation, this study will evaluate whether&#xD;
      doubling the dose to 120 mg/kg/week has an effect in decreasing lung inflammation.&#xD;
&#xD;
      Only the dosing of 60 mg/kg /week has received FDA approval. FDA has granted an IND number to&#xD;
      this study to test the higher dose of 120 mg/kg/week.&#xD;
&#xD;
      The study will evaluate systemic (serum) and pulmonary (bronchoscopy samples)markers of&#xD;
      inflammation in 3 phases: standard dose (4 weeks), double dose (4 weeks) and standard dose (4&#xD;
      weeks).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a pilot study to test the effect of double dose augmentation therapy with Zemaira&#xD;
      (CSL Behring) on lung inflammation, compared with standard doses of 60 mg/kg/week.&#xD;
&#xD;
      Our hypothesis is that some patients with AATD receiving augmentation therapy at the standard&#xD;
      dose of 60 mg/kg/week continue to have a significant lung inflammation that may lead to&#xD;
      detrimental clinical consequences. This inflammation can be further reduced with higher AAT&#xD;
      dosing.&#xD;
&#xD;
      The study will enroll 20 subjects with AATD and COPD already receiving augmentation therapy&#xD;
      with any brand at standard doses for at least a month. For inclusion and exclusion criteria&#xD;
      see below.&#xD;
&#xD;
      Protocol:&#xD;
&#xD;
      The study will take place over approximately 12 weeks: a month receiving Zemaira at standard&#xD;
      dose (60 mg/kg/week), a month at double dose (120 mg/kg/week) and a month at standard dose&#xD;
      (60 mg/kg/week). The infusions at standard doses will be done at home and infusions with&#xD;
      higher doses will be provided at the study site.&#xD;
&#xD;
      the study involves scheduled blood draws for clinical labs and serum for research samples. At&#xD;
      the end of each phase a bronchoscopy will be performed (3 in total) to obtain research&#xD;
      samples (lung lavage, brushings and endobronchial biopsies).&#xD;
&#xD;
      The first bronchoscopy after receiving 4 weeks of standard augmentation therapy will assess&#xD;
      the &quot;residual&quot; inflammation that may be present despite augmentation therapy. The second&#xD;
      bronchoscopy after double dose augmentation therapy phase will be to assess changes&#xD;
      (decreases) in inflammatory markers. The third bronchoscopy after resuming standard dosing is&#xD;
      to assess if inflammation returned to baseline levels (required for proof of concept).&#xD;
&#xD;
      There will be approximately 9 visits to the study clinic. This study does not include placebo&#xD;
      (no active drug) treatment. Besides blood draws and bronchoscopy, the study will include&#xD;
      questionnaires and lung function testing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">May 2016</completion_date>
  <primary_completion_date type="Actual">May 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in Inflammatory Biomarkers in Bronchoalveolar Lavage Fluid</measure>
    <time_frame>Between baseline (week 4), double dose A1PI (week 8) and again standard dose (week 12)</time_frame>
    <description>Assess the variations in the levels of several cytokines and inflammatory biomarkers in BAL after changing A1PI dosing.&#xD;
Measures were done using the bead technology.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Inflammatory Biomarkers in Serum Samples</measure>
    <time_frame>Between baseline (week 4), double dose A1PI (week 8) and again standard dose (week 12)</time_frame>
    <description>Assess the variations in the levels of cytokines and inflammatory biomarkers using the bead technology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Adverse Events Reported</measure>
    <time_frame>From Week 1 to week 12</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Elastin Degradation in BAL</measure>
    <time_frame>Week 4 vs Week 8 vs Week 12</time_frame>
    <description>Desmosine/isodesmosine measured using mass spectometry.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Alpha 1 Antitrypsin Deficiency</condition>
  <arm_group>
    <arm_group_label>Alpha-1 Antitrypsin (human) standard dose baseline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Alpha-1 Antitrypsin (human) 60 mg per kg per week for 4 weeks. Study week 4</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Alpha-1 Antitrypsin (human) Double dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Alpha-1 Antitrypsin (human) 120 mg/kg per week for 4 weeks. Study week 8</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Alpha-1 Antitrypsin (human) standard dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 weeks on A1PI at 60 mg/kg per week after the other 2 phases. Collected@ study week 12</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alpha-1 Antitrypsin (human)</intervention_name>
    <description>Comparison of Zemaira (Alpha 1 Antitrypsin Human) 120 mg/kg/weekly for four weeks versus 2 phases with same drug administered at standard doses of 60 mg/kg/weekly for four weeks each</description>
    <arm_group_label>Alpha-1 Antitrypsin (human) Double dose</arm_group_label>
    <arm_group_label>Alpha-1 Antitrypsin (human) standard dose</arm_group_label>
    <arm_group_label>Alpha-1 Antitrypsin (human) standard dose baseline</arm_group_label>
    <other_name>Zemaira</other_name>
    <other_name>Alpha-1 proteinase inhibitor (human)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males or Females aged between 18 and 75 years.&#xD;
&#xD;
          -  Diagnosis of AATD, based on documentation of &quot;at-risk&quot; genotypes such as Pi ZZ, SZ or&#xD;
             Znull OR documentation of a pre-therapy AAT level &lt; 11 µM.&#xD;
&#xD;
          -  Evidence of COPD (emphysema or airflow obstruction) with FEV1 &lt; 80%&#xD;
&#xD;
          -  Receiving standard dose of augmentation therapy (with any commercial formulation) for&#xD;
             at least 1 month at the dose of 60 mg/kg/week.&#xD;
&#xD;
          -  At least ONE of the following criteria of disease severity:&#xD;
&#xD;
               -  2 or more acute exacerbations or 1 hospitalization due to respiratory symptoms in&#xD;
                  the past 12 months. Definition of exacerbations: the use of antibiotics and a&#xD;
                  course of steroids to treat a flare of pulmonary symptoms, regardless if the&#xD;
                  subject required emergency room care or hospital admission. The diagnosis of the&#xD;
                  acute exacerbation will be obtained by direct history obtained from the patient&#xD;
                  and confirmed by the PI. Attempts should be made to have documentation from the&#xD;
                  patient's treating physicians, although not required for study entry.&#xD;
&#xD;
               -  St. George Respiratory Questionnaire (SGRQ) total score ≥ 60.&#xD;
&#xD;
               -  Chronic bronchitis: daily or almost daily sputum expectoration at least 3 months&#xD;
                  of the year for at least 2 consecutive years. The diagnosis of chronic bronchitis&#xD;
                  will be obtained by direct history obtained from the patient and confirmed by the&#xD;
                  PI. Attempts should be made to have documentation from the patient's treating&#xD;
                  physicians, although not required for study entry.&#xD;
&#xD;
               -  Documented FEV1 decline of at least ≥ 60 ml/year for 2 consecutive years while&#xD;
                  receiving augmentation therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - Patients unsuitable to have a bronchoscopy due to poor clinical condition as judged by&#xD;
        the PI. In general we will exclude subjects with hypoxemia, coagulopathy or FEV1 below 40%&#xD;
        predicted.&#xD;
&#xD;
        Note: Subjects with FEV1 values below 40% predicted may be included and reassessed after&#xD;
        optimization of therapy. Final determination to include the patient if deemed suitable for&#xD;
        the procedure will be determined by the PI before first planned bronchoscopy (regardless of&#xD;
        FEV1 value).&#xD;
&#xD;
          -  Patients participating in other clinical trials.&#xD;
&#xD;
          -  Use of chronic antibiotics or oral steroids&#xD;
&#xD;
          -  Continues to smoke&#xD;
&#xD;
          -  Inability to sign informed consent&#xD;
&#xD;
          -  Pregnancy or willing to become pregnant&#xD;
&#xD;
          -  Known IgA deficiency (we will include only patients already receiving augmentation&#xD;
             therapy so it will be unlikely to encounter this exclusion criteria)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael A Campos, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Miami</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Division of Pulmonary and Critical Care, Human Reseach, U of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Tonelli AR, Brantly ML. Augmentation therapy in alpha-1 antitrypsin deficiency: advances and controversies. Ther Adv Respir Dis. 2010 Oct;4(5):289-312. doi: 10.1177/1753465810373911. Epub 2010 Jul 22.</citation>
    <PMID>20650978</PMID>
  </reference>
  <reference>
    <citation>Stockley RA, Bayley DL, Unsal I, Dowson LJ. The effect of augmentation therapy on bronchial inflammation in alpha1-antitrypsin deficiency. Am J Respir Crit Care Med. 2002 Jun 1;165(11):1494-8. doi: 10.1164/rccm.2109013.</citation>
    <PMID>12045122</PMID>
  </reference>
  <reference>
    <citation>Petrache I, Hajjar J, Campos M. Safety and efficacy of alpha-1-antitrypsin augmentation therapy in the treatment of patients with alpha-1-antitrypsin deficiency. Biologics. 2009;3:193-204. doi: 10.2147/btt.2009.3088. Epub 2009 Jul 13.</citation>
    <PMID>19707408</PMID>
  </reference>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>August 14, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2012</study_first_posted>
  <results_first_submitted>August 23, 2017</results_first_submitted>
  <results_first_submitted_qc>April 17, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">May 8, 2019</results_first_posted>
  <last_update_submitted>April 17, 2019</last_update_submitted>
  <last_update_submitted_qc>April 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Miami</investigator_affiliation>
    <investigator_full_name>Michael Campos, MD</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Alpha 1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Alpha 1-Antitrypsin Deficiency</mesh_term>
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Protease Inhibitors</mesh_term>
    <mesh_term>Alpha 1-Antitrypsin</mesh_term>
    <mesh_term>Protein C Inhibitor</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Studied Population</title>
          <description>All patients belong to one study arm. First they received standard dose augmentation therapy (60 mg/kg/week) x 4 weeks, then they receive experimental double dose (120 mg/kg/week) x 4 weeks and finally return to standard dose (60 mg/kg/week) for 4 additional weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Phase 1: Standard Dose Therapy</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Phase 2: Double Dose Therapy</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Phase 3: Standard Dose Therapy</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Alpha-1 Antitrypsin (Human)</title>
          <description>Alpha-1 Antitrypsin (human) 120 mg per kg per week for 4 weeks&#xD;
Alpha-1 Antitrypsin (human): Comparison of Zemaira (Alpha 1 Antitrypsin Human) 120 mg/kg/weekly for four weeks versus 2 phases with same drug administered at standard doses of 60 mg/kg/weekly for four weeks each</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.6" spread="8.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Changes in Inflammatory Biomarkers in Bronchoalveolar Lavage Fluid</title>
        <description>Assess the variations in the levels of several cytokines and inflammatory biomarkers in BAL after changing A1PI dosing.&#xD;
Measures were done using the bead technology.</description>
        <time_frame>Between baseline (week 4), double dose A1PI (week 8) and again standard dose (week 12)</time_frame>
        <population>Subjects with AATD and COPD that require augmentation therapy</population>
        <group_list>
          <group group_id="O1">
            <title>Alpha-1 Antitrypsin (Human) Standard Dose Baseline</title>
            <description>Alpha-1 Antitrypsin (human) 60 mg per kg per week for 4 weeks. Study week 4</description>
          </group>
          <group group_id="O2">
            <title>Alpha-1 Antitrypsin (Human) Double Dose</title>
            <description>Alpha-1 Antitrypsin (human) 120 mg/kg per week for 4 weeks. Study week 8</description>
          </group>
          <group group_id="O3">
            <title>Alpha-1 Antitrypsin (Human) Standard Dose</title>
            <description>4 weeks on A1PI at 60 mg/kg per week after the other 2 phases. Collected@ study week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Inflammatory Biomarkers in Bronchoalveolar Lavage Fluid</title>
          <description>Assess the variations in the levels of several cytokines and inflammatory biomarkers in BAL after changing A1PI dosing.&#xD;
Measures were done using the bead technology.</description>
          <population>Subjects with AATD and COPD that require augmentation therapy</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>IL-2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.3" spread="7.3"/>
                    <measurement group_id="O2" value="8.1" spread="3.1"/>
                    <measurement group_id="O3" value="10.3" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="379.9" spread="294.3"/>
                    <measurement group_id="O2" value="563.2" spread="317.8"/>
                    <measurement group_id="O3" value="412.2" spread="160.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-17</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79.0" spread="27.8"/>
                    <measurement group_id="O2" value="61.5" spread="15.8"/>
                    <measurement group_id="O3" value="67.4" spread="8.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BASIC FGF</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.7" spread="9.3"/>
                    <measurement group_id="O2" value="15.4" spread="4.3"/>
                    <measurement group_id="O3" value="16.5" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>GM-CSF</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="114.9" spread="36.2"/>
                    <measurement group_id="O2" value="89.1" spread="33.6"/>
                    <measurement group_id="O3" value="105.4" spread="20.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="116.5" spread="68.4"/>
                    <measurement group_id="O2" value="92.5" spread="38.9"/>
                    <measurement group_id="O3" value="90.5" spread="16.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL1alpha</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.7" spread="18.7"/>
                    <measurement group_id="O2" value="27.4" spread="18.8"/>
                    <measurement group_id="O3" value="27.7" spread="6.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.1" spread="7.4"/>
                    <measurement group_id="O2" value="8.1" spread="2.0"/>
                    <measurement group_id="O3" value="7.7" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M-CSF</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.1" spread="18.9"/>
                    <measurement group_id="O2" value="37.0" spread="33.4"/>
                    <measurement group_id="O3" value="33.1" spread="19.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.1" spread="0.6"/>
                    <measurement group_id="O2" value="3.0" spread="0.5"/>
                    <measurement group_id="O3" value="2.9" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-9</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.9" spread="4.8"/>
                    <measurement group_id="O2" value="23.1" spread="4.1"/>
                    <measurement group_id="O3" value="23.5" spread="3.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eotaxin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="154.0" spread="37.7"/>
                    <measurement group_id="O2" value="150.9" spread="44.6"/>
                    <measurement group_id="O3" value="138.0" spread="16.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>IL-2</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Data was analyzed with multiple repeat ANOVA for all visits and paired samples were also evaluated.</non_inferiority_desc>
            <p_value>&lt;0.05</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>IL-4</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Kruskal-Wallis</non_inferiority_desc>
            <p_value>0.035</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>IL-8</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.33</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>IL-9</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.68</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>IL-17</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.020</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>FGF</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.021</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Eotaxin</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.02</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>GM-CSF</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.045</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>IL15</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.47</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>IL-1a</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.90</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>IL18</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.80</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>M-CSF</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.027</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Inflammatory Biomarkers in Serum Samples</title>
        <description>Assess the variations in the levels of cytokines and inflammatory biomarkers using the bead technology.</description>
        <time_frame>Between baseline (week 4), double dose A1PI (week 8) and again standard dose (week 12)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Alpha-1 Antitrypsin (Human) Standard Dose Baseline</title>
            <description>Alpha-1 Antitrypsin (human) 60 mg per kg per week for 4 weeks</description>
          </group>
          <group group_id="O2">
            <title>Alpha-1 Antitrypsin (Human) Double Dose</title>
            <description>A1PI at 120 mg/kg per week for 4 weeks after subjects received 4 weeks standard dose</description>
          </group>
          <group group_id="O3">
            <title>Alpha-1 Antitrypsin (Human) Standard Dose</title>
            <description>4 weeks on A1PI at 60 mg/kg per week after the other 2 phases. Collected@ study week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Inflammatory Biomarkers in Serum Samples</title>
          <description>Assess the variations in the levels of cytokines and inflammatory biomarkers using the bead technology.</description>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>IL-2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="127.3" spread="114.0"/>
                    <measurement group_id="O2" value="114.5" spread="81.6"/>
                    <measurement group_id="O3" value="66.11" spread="95.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="232.3" spread="212.0"/>
                    <measurement group_id="O2" value="222.4" spread="202.2"/>
                    <measurement group_id="O3" value="132.56" spread="161.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-1beta</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.2" spread="11.6"/>
                    <measurement group_id="O2" value="9.1" spread="7.7"/>
                    <measurement group_id="O3" value="34.06" spread="73.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.5" spread="11.6"/>
                    <measurement group_id="O2" value="13.3" spread="9.4"/>
                    <measurement group_id="O3" value="9.73" spread="11.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.8" spread="86.3"/>
                    <measurement group_id="O2" value="72.9" spread="58.1"/>
                    <measurement group_id="O3" value="50.62" spread="74.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IFNy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.4" spread="67.9"/>
                    <measurement group_id="O2" value="67" spread="49.1"/>
                    <measurement group_id="O3" value="48.9" spread="63.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CRP</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="476.7" spread="358.9"/>
                    <measurement group_id="O2" value="1082.9" spread="1971.9"/>
                    <measurement group_id="O3" value="494.5" spread="453.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>No power calculation and this is an exploratory pilot analysis We expected cytokines to decrease after subjects receive double dose and a rebound after administering standard dose.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.07</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Adverse Events Reported</title>
        <time_frame>From Week 1 to week 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Alpha-1 Antitrypsin (Human) Standard Dose Baseline</title>
            <description>Alpha-1 Antitrypsin (human) 60 mg per kg per week for 4 weeks</description>
          </group>
          <group group_id="O2">
            <title>Alpha-1 Antitrypsin (Human) Double Dose</title>
            <description>A1PI at 120 mg/kg per week for 4 weeks after subjects received 4 weeks standard dose</description>
          </group>
          <group group_id="O3">
            <title>Alpha-1 Antitrypsin (Human) Standard Dose</title>
            <description>60 mg/kg per week after the prior 2 phases</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Adverse Events Reported</title>
          <units>Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Elastin Degradation in BAL</title>
        <description>Desmosine/isodesmosine measured using mass spectometry.</description>
        <time_frame>Week 4 vs Week 8 vs Week 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Alpha-1 Antitrypsin (Human) Standard Dose Baseline</title>
            <description>Alpha-1 Antitrypsin (human) 60 mg/kg per week for 4 weeks (measure at week 4)</description>
          </group>
          <group group_id="O2">
            <title>Alpha-1 Antitrypsin (Human) Double Dose</title>
            <description>A1PI at 120 mg/kg per week x 4 weeks (measure at week 8)</description>
          </group>
          <group group_id="O3">
            <title>Alpha-1 Antitrypsin (Human) Standard Dose</title>
            <description>A1PI at 60 mg/kg per week after double dose (measured at week 12)</description>
          </group>
        </group_list>
        <measure>
          <title>Elastin Degradation in BAL</title>
          <description>Desmosine/isodesmosine measured using mass spectometry.</description>
          <units>ng/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="156.7" spread="103.2"/>
                    <measurement group_id="O2" value="62.89" spread="23.55"/>
                    <measurement group_id="O3" value="56.88" spread="25.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Desmosine (DES) and isodesmosine (IDES) are used as indicator of elastin degradation. Levels of DES/IDES were measured using high-performance liquid chromatography and tandem mass spectrometry.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>between Week 4 and Week 8</non_inferiority_desc>
            <p_value>0.03</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>between Week 8 and Week 12</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.33</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>between Week 4 and Week 12</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.029</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event was recorded for each subject from study enrollment (day 0) through study end which was on the day of the last bronchoscopy at the end of phase 3 (week 12). Each subject was assessed weekly by phone calls and in-person at the end of each phase (day of bronchoscopies).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Phase 1: Standard Dose</title>
          <description>Standard dose (60 mg/kg/week) Weeks1-4</description>
        </group>
        <group group_id="E2">
          <title>Phase 2: Double Dose</title>
          <description>Double dose (120 mg/kg/week) weeks 4-8</description>
        </group>
        <group group_id="E3">
          <title>Phase 3: Standard Dose</title>
          <description>Standard dose (60 mg/kg/week) weeks 8-12</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hemoptysis</sub_title>
                <description>1 patient developed mild hemoptysis after bronchoscopy # 1 and withdrew from study</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Respiratory distress</sub_title>
                <description>1 patient developed respiratory distress after bronchoscopy # 1 and PI withdrew pt from study</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Michael Campos</name_or_title>
      <organization>University of Miami</organization>
      <phone>305-243-3045</phone>
      <email>mcampos1@med.miami.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01669421
org study id: 20100844
nct id: NCT01669421
lead sponsor: 
collaborator: 
has dmc: No
The current treatment of individuals with alpha-1 antitrypsin deficiency (AATD) who develop
      lung disease (COPD) is the administration of intravenous purified alpha-1 antitrypsin
      (augmentation therapy) at a fixed dose of 60 mg/kg per week. This dose aims at increasing the
      deficient AAT serum levels just above a predetermined "safety threshold" of 11 uM. However,
      normal levels of AAT are between 25-50 uM.

      AAT has shown not only to inhibit lung proteases such as neutrophil elastase, but also to
      modulate inflammation. Given that many subjects with AATD who receive augmentation therapy
      still have significant lung disease and inflammation, this study will evaluate whether
      doubling the dose to 120 mg/kg/week has an effect in decreasing lung inflammation.

      Only the dosing of 60 mg/kg /week has received FDA approval. FDA has granted an IND number to
      this study to test the higher dose of 120 mg/kg/week.

      The study will evaluate systemic (serum) and pulmonary (bronchoscopy samples)markers of
      inflammation in 3 phases: standard dose (4 weeks), double dose (4 weeks) and standard dose (4
      weeks).
This is a pilot study to test the effect of double dose augmentation therapy with Zemaira
      (CSL Behring) on lung inflammation, compared with standard doses of 60 mg/kg/week.

      Our hypothesis is that some patients with AATD receiving augmentation therapy at the standard
      dose of 60 mg/kg/week continue to have a significant lung inflammation that may lead to
      detrimental clinical consequences. This inflammation can be further reduced with higher AAT
      dosing.

      The study will enroll 20 subjects with AATD and COPD already receiving augmentation therapy
      with any brand at standard doses for at least a month. For inclusion and exclusion criteria
      see below.

      Protocol:

      The study will take place over approximately 12 weeks: a month receiving Zemaira at standard
      dose (60 mg/kg/week), a month at double dose (120 mg/kg/week) and a month at standard dose
      (60 mg/kg/week). The infusions at standard doses will be done at home and infusions with
      higher doses will be provided at the study site.

      the study involves scheduled blood draws for clinical labs and serum for research samples. At
      the end of each phase a bronchoscopy will be performed (3 in total) to obtain research
      samples (lung lavage, brushings and endobronchial biopsies).

      The first bronchoscopy after receiving 4 weeks of standard augmentation therapy will assess
      the "residual" inflammation that may be present despite augmentation therapy. The second
      bronchoscopy after double dose augmentation therapy phase will be to assess changes
      (decreases) in inflammatory markers. The third bronchoscopy after resuming standard dosing is
      to assess if inflammation returned to baseline levels (required for proof of concept).

      There will be approximately 9 visits to the study clinic. This study does not include placebo
      (no active drug) treatment. Besides blood draws and bronchoscopy, the study will include
      questionnaires and lung function testing.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Changes in Inflammatory Biomarkers in Bronchoalveolar Lavage Fluid
time frame: Between baseline (week 4), double dose A1PI (week 8) and again standard dose (week 12)
description: Assess the variations in the levels of several cytokines and inflammatory biomarkers in BAL after changing A1PI dosing.
Measures were done using the bead technology.
measure: Change in Inflammatory Biomarkers in Serum Samples
time frame: Between baseline (week 4), double dose A1PI (week 8) and again standard dose (week 12)
description: Assess the variations in the levels of cytokines and inflammatory biomarkers using the bead technology.
measure: Number of Adverse Events Reported
time frame: From Week 1 to week 12
measure: Elastin Degradation in BAL
time frame: Week 4 vs Week 8 vs Week 12
description: Desmosine/isodesmosine measured using mass spectometry.
arm group label: Alpha-1 Antitrypsin (human) standard dose baseline
arm group type: Experimental
description: Alpha-1 Antitrypsin (human) 60 mg per kg per week for 4 weeks. Study week 4
arm group label: Alpha-1 Antitrypsin (human) Double dose
arm group type: Experimental
description: Alpha-1 Antitrypsin (human) 120 mg/kg per week for 4 weeks. Study week 8
arm group label: Alpha-1 Antitrypsin (human) standard dose
arm group type: Experimental
description: 4 weeks on A1PI at 60 mg/kg per week after the other 2 phases. Collected@ study week 12
intervention type: Drug
intervention name: Alpha-1 Antitrypsin (human)
description: Comparison of Zemaira (Alpha 1 Antitrypsin Human) 120 mg/kg/weekly for four weeks versus 2 phases with same drug administered at standard doses of 60 mg/kg/weekly for four weeks each
arm group label: Alpha-1 Antitrypsin (human) Double dose
arm group label: Alpha-1 Antitrypsin (human) standard dose
arm group label: Alpha-1 Antitrypsin (human) standard dose baseline
other name: Zemaira
other name: Alpha-1 proteinase inhibitor (human)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Michael A Campos, MD
role: Principal Investigator
affiliation: University of Miami
facility: 
country: United States
citation: Tonelli AR, Brantly ML. Augmentation therapy in alpha-1 antitrypsin deficiency: advances and controversies. Ther Adv Respir Dis. 2010 Oct;4(5):289-312. doi: 10.1177/1753465810373911. Epub 2010 Jul 22.
PMID: 20650978
citation: Stockley RA, Bayley DL, Unsal I, Dowson LJ. The effect of augmentation therapy on bronchial inflammation in alpha1-antitrypsin deficiency. Am J Respir Crit Care Med. 2002 Jun 1;165(11):1494-8. doi: 10.1164/rccm.2109013.
PMID: 12045122
citation: Petrache I, Hajjar J, Campos M. Safety and efficacy of alpha-1-antitrypsin augmentation therapy in the treatment of patients with alpha-1-antitrypsin deficiency. Biologics. 2009;3:193-204. doi: 10.2147/btt.2009.3088. Epub 2009 Jul 13.
PMID: 19707408
responsible party type: Sponsor-Investigator
investigator affiliation: University of Miami
investigator full name: Michael Campos, MD
investigator title: Associate Professor
mesh term: Pneumonia
mesh term: Alpha 1-Antitrypsin Deficiency
mesh term: Inflammation
mesh term: Protease Inhibitors
mesh term: Alpha 1-Antitrypsin
mesh term: Protein C Inhibitor
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 