<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/NCT04474197</url>
  </required_header>
  <id_info>
    <org_study_id>VX19-864-101</org_study_id>
    <secondary_id>2019-004881-16</secondary_id>
    <nct_id>NCT04474197</nct_id>
  </id_info>
  <brief_title>Evaluation of the Efficacy and Safety of VX-864 in Subjects With the PiZZ Genotype</brief_title>
  <official_title>A Phase 2, Randomized, Double-blind, Placebo-controlled Study of the Efficacy and Safety of VX-864 in PiZZ Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vertex Pharmaceuticals Incorporated</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vertex Pharmaceuticals Incorporated</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the efficacy, safety and pharmacokinetics (PK) of VX-864 in PiZZ&#xD;
      subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 24, 2020</start_date>
  <completion_date type="Actual">May 4, 2021</completion_date>
  <primary_completion_date type="Actual">May 4, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Plasma Functional Alpha-1 Antitrypsin (AAT) Levels</measure>
    <time_frame>From Baseline at Day 28</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>Day 1 up to Week 8</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Plasma Antigenic AAT Levels</measure>
    <time_frame>From Baseline at Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Observed Pre-dose Plasma Concentration (Ctrough) of VX-864</measure>
    <time_frame>Pre-dose at Day 7, Day 14, Day 21 and Day 28</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Alpha1-Antitrypsin Deficiency</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants received placebo matched to VX-864 in the treatment period for 28 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>VX-864 100 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received VX-864 100 milligrams (mg) every 12 hours (q12h) in the treatment period for 28 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>VX-864 300 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received VX-864 300 mg q12h in the treatment period for 28 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>VX-864 500 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received VX-864 500 mg q12h in the treatment period for 28 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>VX-864</intervention_name>
    <description>Tablets for oral administration.</description>
    <arm_group_label>VX-864 100 mg</arm_group_label>
    <arm_group_label>VX-864 300 mg</arm_group_label>
    <arm_group_label>VX-864 500 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo matched to VX-864 for oral administration.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must have a PiZZ genotype confirmed at screening&#xD;
&#xD;
          -  Plasma AAT levels indicating severe deficiency at screening&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  History of a medical condition that could negatively impact the ability to complete&#xD;
             the study&#xD;
&#xD;
          -  Solid organ, or hematological transplantation or is currently on a transplant list&#xD;
&#xD;
          -  History of use of gene therapy or RNAi therapy at any time previously&#xD;
&#xD;
        Other protocol defined Inclusion/Exclusion criteria may apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>David Geffen School of Medicine at UCLA</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Davis Medical Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Jewish Health</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>11735</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami Miller School of Medicine</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Florida Pulmonary</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Iowa Hospitals and Clinics</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Blessing Corporate Services, Inc., dba Blessing Health System</name>
      <address>
        <city>Hannibal</city>
        <state>Missouri</state>
        <zip>63401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cardinal Glennon Children's Hospital - St. Louis University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina Medical Center</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest University Baptist Medical Center</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Temple University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Renovatio Clinical</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77380</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas Health Science Center at Tyler</name>
      <address>
        <city>Tyler</city>
        <state>Texas</state>
        <zip>75708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah Health</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inova Fairfax Medical Campus</name>
      <address>
        <city>Falls Church</city>
        <state>Virginia</state>
        <zip>22042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth II Health Sciences Center</name>
      <address>
        <city>Halifax</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inspiration Research Ltd</name>
      <address>
        <city>Toronto</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital RWTH Aachen</name>
      <address>
        <city>Aachen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Essen</name>
      <address>
        <city>Essen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Hochschule Hannover</name>
      <address>
        <city>Hannover</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal College of Surgeons in Ireland Clinical Research Centre, Beaumont Hospital</name>
      <address>
        <city>Beaumont</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Skanes Universitetssjukhus, Malmo</name>
      <address>
        <city>Malmö</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Staploe Medical Centre</name>
      <address>
        <city>Soham Ely</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Germany</country>
    <country>Ireland</country>
    <country>Sweden</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <results_first_submitted>May 3, 2022</results_first_submitted>
  <results_first_submitted_qc>May 3, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">May 26, 2022</results_first_posted>
  <last_update_submitted>May 3, 2022</last_update_submitted>
  <last_update_submitted_qc>May 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 26, 2022</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>Alpha 1-Antitrypsin Deficiency</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 12, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/97/NCT04474197/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 11, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/97/NCT04474197/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>This study was conducted in participants 18 through 80 of years of age, inclusive with the PiZZ genotype.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Participants received placebo matched to VX-864 in the treatment period for 28 days.</description>
        </group>
        <group group_id="P2">
          <title>VX-864 100 mg</title>
          <description>Participants received VX-864 100 milligrams (mg) every 12 hours (q12h) in the treatment period for 28 days.</description>
        </group>
        <group group_id="P3">
          <title>VX-864 300 mg</title>
          <description>Participants received VX-864 300 mg q12h in the treatment period for 28 days.</description>
        </group>
        <group group_id="P4">
          <title>VX-864 500 mg</title>
          <description>Participants received VX-864 500 mg q12h in the treatment period for 28 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="9"/>
                <participants group_id="P4" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="9"/>
                <participants group_id="P4" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal of consent (not due to adverse event)</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Participants received placebo matched to VX-864 in the treatment period for 28 days.</description>
        </group>
        <group group_id="B2">
          <title>VX-864 100 mg</title>
          <description>Participants received VX-864 100 mg q12h in the treatment period for 28 days.</description>
        </group>
        <group group_id="B3">
          <title>VX-864 300 mg</title>
          <description>Participants received VX-864 300 mg q12h in the treatment period for 28 days.</description>
        </group>
        <group group_id="B4">
          <title>VX-864 500 mg</title>
          <description>Participants received VX-864 500 mg q12h in the treatment period for 28 days.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="7"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="9"/>
            <count group_id="B4" value="18"/>
            <count group_id="B5" value="44"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="63.4" spread="10.5"/>
                    <measurement group_id="B2" value="55.1" spread="5.3"/>
                    <measurement group_id="B3" value="53.2" spread="16.2"/>
                    <measurement group_id="B4" value="57.4" spread="9.9"/>
                    <measurement group_id="B5" value="57.0" spread="10.9"/>
                  </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="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="14"/>
                    <measurement group_id="B5" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="15"/>
                    <measurement group_id="B5" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="18"/>
                    <measurement group_id="B5" value="44"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Plasma Functional Alpha-1 Antitrypsin (AAT) Levels</title>
          <units>micromole per liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.7" spread="1.3"/>
                    <measurement group_id="B2" value="4.0" spread="0.7"/>
                    <measurement group_id="B3" value="3.8" spread="0.9"/>
                    <measurement group_id="B4" value="4.1" spread="0.6"/>
                    <measurement group_id="B5" value="4.1" spread="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Plasma Functional Alpha-1 Antitrypsin (AAT) Levels</title>
        <time_frame>From Baseline at Day 28</time_frame>
        <population>Full analysis set (FAS) included all randomized participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to VX-864 in the treatment period for 28 days.</description>
          </group>
          <group group_id="O2">
            <title>VX-864 100 mg</title>
            <description>Participants received VX-864 100 mg q12h in the treatment period for 28 days.</description>
          </group>
          <group group_id="O3">
            <title>VX-864 300 mg</title>
            <description>Participants received VX-864 300 mg dose q12h in the treatment period for 28 days.</description>
          </group>
          <group group_id="O4">
            <title>VX-864 500 mg</title>
            <description>Participants received VX-864 500 mg dose q12h in the treatment period for 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Plasma Functional Alpha-1 Antitrypsin (AAT) Levels</title>
          <population>Full analysis set (FAS) included all randomized participants who received at least 1 dose of study drug.</population>
          <units>micromole per liter</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="0.3"/>
                    <measurement group_id="O2" value="2.3" spread="0.3"/>
                    <measurement group_id="O3" value="2.3" spread="0.2"/>
                    <measurement group_id="O4" value="2.1" spread="0.2"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Mixed-effects Model for Repeated Measure</method>
            <param_type>Least Squares (LS) Mean Difference</param_type>
            <param_value>2.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.5</ci_lower_limit>
            <ci_upper_limit>3.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Mixed-effects Model for Repeated Measure</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>2.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.6</ci_lower_limit>
            <ci_upper_limit>3.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Mixed-effects Model for Repeated Measure</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>2.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.5</ci_lower_limit>
            <ci_upper_limit>2.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
        <time_frame>Day 1 up to Week 8</time_frame>
        <population>The safety set included all participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to VX-864 in the treatment period for 28 days.</description>
          </group>
          <group group_id="O2">
            <title>VX-864 100 mg</title>
            <description>Participants received VX-864 100 mg q12h in the treatment period for 28 days.</description>
          </group>
          <group group_id="O3">
            <title>VX-864 300 mg</title>
            <description>Participants received VX-864 300 mg q12h in the treatment period for 28 days.</description>
          </group>
          <group group_id="O4">
            <title>VX-864 500 mg</title>
            <description>Participants received VX-864 500 mg q12h in the treatment period for 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
          <population>The safety set included all participants who received at least 1 dose of study drug.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants With AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="7"/>
                    <measurement group_id="O4" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants With SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Plasma Antigenic AAT Levels</title>
        <time_frame>From Baseline at Day 28</time_frame>
        <population>FAS.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to VX-864 in the treatment period for 28 days.</description>
          </group>
          <group group_id="O2">
            <title>VX-864 100 mg</title>
            <description>Participants received VX-864 100 mg q12h in the treatment period for 28 days.</description>
          </group>
          <group group_id="O3">
            <title>VX-864 300 mg</title>
            <description>Participants received VX-864 300 mg q12h in the treatment period for 28 days.</description>
          </group>
          <group group_id="O4">
            <title>VX-864 500 mg</title>
            <description>Participants received VX-864 500 mg q12h in the treatment period for 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Plasma Antigenic AAT Levels</title>
          <population>FAS.</population>
          <units>micromole per liter</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="0.4"/>
                    <measurement group_id="O2" value="3.4" spread="0.4"/>
                    <measurement group_id="O3" value="2.9" spread="0.4"/>
                    <measurement group_id="O4" value="2.6" spread="0.2"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Mixed-effects Model for Repeated Measure</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>3.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.4</ci_lower_limit>
            <ci_upper_limit>4.6</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Mixed-effects Model for Repeated Measure</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>3.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.9</ci_lower_limit>
            <ci_upper_limit>4.0</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Mixed-effects Model for Repeated Measure</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>2.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.8</ci_lower_limit>
            <ci_upper_limit>3.7</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Observed Pre-dose Plasma Concentration (Ctrough) of VX-864</title>
        <time_frame>Pre-dose at Day 7, Day 14, Day 21 and Day 28</time_frame>
        <population>Pharmacokinetic (PK) set included participants who received at least 1 dose of study drug. Here &quot;Number analyzed&quot; signifies those participants who were evaluable for this endpoint at specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>VX-864 100 mg</title>
            <description>Participants received VX-864 100 mg q12h in the treatment period for 28 days.</description>
          </group>
          <group group_id="O2">
            <title>VX-864 300 mg</title>
            <description>Participants received VX-864 300 mg q12h in the treatment period for 28 days.</description>
          </group>
          <group group_id="O3">
            <title>VX-864 500 mg</title>
            <description>Participants received VX-864 500 mg q12h in the treatment period for 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Observed Pre-dose Plasma Concentration (Ctrough) of VX-864</title>
          <population>Pharmacokinetic (PK) set included participants who received at least 1 dose of study drug. Here &quot;Number analyzed&quot; signifies those participants who were evaluable for this endpoint at specified time points.</population>
          <units>microgram per milliliter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="8"/>
                    <count group_id="O3" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.13" spread="0.743"/>
                    <measurement group_id="O2" value="1.62" spread="0.665"/>
                    <measurement group_id="O3" value="2.74" spread="2.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="9"/>
                    <count group_id="O3" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.852" spread="0.340"/>
                    <measurement group_id="O2" value="1.47" spread="0.847"/>
                    <measurement group_id="O3" value="4.35" spread="5.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="8"/>
                    <count group_id="O3" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.868" spread="0.503"/>
                    <measurement group_id="O2" value="1.21" spread="0.770"/>
                    <measurement group_id="O3" value="1.79" spread="0.922"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="8"/>
                    <count group_id="O3" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.797" spread="0.327"/>
                    <measurement group_id="O2" value="1.29" spread="0.646"/>
                    <measurement group_id="O3" value="2.55" spread="2.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day 1 up to Week 8</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Participants received placebo matched to VX-864 in the treatment period for 28 days.</description>
        </group>
        <group group_id="E2">
          <title>VX-864 100 mg</title>
          <description>Participants received VX-864 100 mg q12h in the treatment period for 28 days.</description>
        </group>
        <group group_id="E3">
          <title>VX-864 300 mg</title>
          <description>Participants received VX-864 300 mg q12h in the treatment period for 28 days.</description>
        </group>
        <group group_id="E4">
          <title>VX-864 500 mg</title>
          <description>Participants received VX-864 500 mg q12h in the treatment period for 28 days.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>Meddra 24.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumothorax spontaneous</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 24.0</default_vocab>
        <default_assessment>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="4" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="17" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye allergy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Macular degeneration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Gingival pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Feeling abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Feeling cold</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infective exacerbation of bronchiectasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Back injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Muscle strain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Post procedural contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Skin laceration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Vaccination complication</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood bicarbonate decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood cholesterol increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood potassium decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood pressure diastolic increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood triglycerides increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Haemoglobin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Low density lipoprotein increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Oxygen saturation decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Protein total decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Red blood cell count increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>White blood cells urine positive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Carpal tunnel syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dysaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Poor quality sleep</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Heavy menstrual bleeding</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Vaginal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Respiration abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Sinus congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Sneezing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Sputum increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Tachypnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Photosensitivity reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Polymorphic light eruption</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="18"/>
              </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 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>Medical Monitor</name_or_title>
      <organization>Vertex Pharmaceuticals Incorporated</organization>
      <phone>617-341-6777</phone>
      <email>medicalinfo@vrtx.com</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/NCT04474197
org study id: VX19-864-101
secondary id: 2019-004881-16
nct id: NCT04474197
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate the efficacy, safety and pharmacokinetics (PK) of VX-864 in PiZZ
      subjects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Plasma Functional Alpha-1 Antitrypsin (AAT) Levels
time frame: From Baseline at Day 28
measure: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: Day 1 up to Week 8
measure: Change in Plasma Antigenic AAT Levels
time frame: From Baseline at Day 28
measure: Observed Pre-dose Plasma Concentration (Ctrough) of VX-864
time frame: Pre-dose at Day 7, Day 14, Day 21 and Day 28
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants received placebo matched to VX-864 in the treatment period for 28 days.
arm group label: VX-864 100 mg
arm group type: Experimental
description: Participants received VX-864 100 milligrams (mg) every 12 hours (q12h) in the treatment period for 28 days.
arm group label: VX-864 300 mg
arm group type: Experimental
description: Participants received VX-864 300 mg q12h in the treatment period for 28 days.
arm group label: VX-864 500 mg
arm group type: Experimental
description: Participants received VX-864 500 mg q12h in the treatment period for 28 days.
intervention type: Drug
intervention name: VX-864
description: Tablets for oral administration.
arm group label: VX-864 100 mg
arm group label: VX-864 300 mg
arm group label: VX-864 500 mg
intervention type: Drug
intervention name: Placebo
description: Placebo matched to VX-864 for oral administration.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
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country: Canada
country: Germany
country: Ireland
country: Sweden
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Alpha 1-Antitrypsin Deficiency
sharing ipd: No
ipd description: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 