<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/NCT03256799</url>
  </required_header>
  <id_info>
    <org_study_id>F161208009</org_study_id>
    <nct_id>NCT03256799</nct_id>
  </id_info>
  <brief_title>Evaluation of Ivacaftor in Patients Using Ataluren for Nonsense Mutations</brief_title>
  <official_title>An Open Label Study to Investigate the Role of Ivacaftor for the Treatment of Cystic Fibrosis in Combination With Ataluren (PTC124) in Cystic Fibrosis Patients Using Ataluren for Nonsense Mutations</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Alabama at Birmingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Alabama at Birmingham</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to explore the combination of Ataluren and ivacaftor as a&#xD;
      treatment for patients with a specific cystic fibrosis mutation&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In about 10% of patients with CF, the defect in the gene is known as a stop mutation. This&#xD;
      mutation truncates the cystic fibrosis transductive regulator (CFTR) protein production by&#xD;
      introducing a premature stop in the messenger RNA (mRNA), this type of mutation is known as a&#xD;
      stop mutation. Ataluren is a novel, oral drug that promotes this gene to work effectively and&#xD;
      readthrough that premature &quot;stop sign&quot;. It is hypothesized that ivacaftor may increase the&#xD;
      efficacy of Ataluren by activating a specific protein that may not be functioning properly.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 17, 2017</start_date>
  <completion_date type="Actual">February 16, 2018</completion_date>
  <primary_completion_date type="Actual">July 10, 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Lung Function</measure>
    <time_frame>Baseline through 48 weeks</time_frame>
    <description>change in lung function as measured by spirometry</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>Ivacaftor/Ataluren</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ivacaftor/Ataluren</intervention_name>
    <description>Both drugs were given in combination for 48 week study period</description>
    <arm_group_label>Ivacaftor/Ataluren</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Evidence of signed and dated informed consent/assent document(s) indicating that the&#xD;
             subject (and/or his parent/legal guardian) has been informed of all pertinent aspects&#xD;
             of the trial.&#xD;
&#xD;
          2. Age ≥19 years&#xD;
&#xD;
          3. Body weight ≥16 kg&#xD;
&#xD;
          4. Diagnosis of cystic fibrosis and documentation of the presence of a nonsense mutations&#xD;
             of the CFTR gene, as determined by historical genotyping&#xD;
&#xD;
          5. Ability to perform a valid, reproducible spirometry with demonstration of a forced&#xD;
             expiratory volume in 1second (FEV1) ≥30% of predicted for age, gender, and height.&#xD;
&#xD;
          6. If the subject is sexually active, willingness to abstain from sexual intercourse or&#xD;
             employ a barrier or medical method of contraception during the study drug&#xD;
             administration&#xD;
&#xD;
          7. Willingness and ability to comply with all study procedures and assessments.&#xD;
&#xD;
          8. Currently receiving Ataluren for nonsense mutations through other clinical trial&#xD;
             access.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any change (initiation, change in type of drug, dose modification, schedule&#xD;
             modification, interruption, discontinuation, or re-initiation) in a chronic&#xD;
             treatment/prophylaxis regimen for CF or for CF-related conditions within 2 weeks prior&#xD;
             to screening.&#xD;
&#xD;
          2. Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection&#xD;
             (including viral illnesses) within 2 weeks prior to screening.&#xD;
&#xD;
          3. Ongoing immunosuppressive therapy (other than corticosteroids up to 10mg/d equivalent&#xD;
             of prednisone)&#xD;
&#xD;
          4. Ongoing warfarin, phenytoin, or tolbutamide therapy.&#xD;
&#xD;
          5. History of solid organ or hematological transplantation.&#xD;
&#xD;
          6. A history of positive hepatitis B surface antigen test, hepatitis C antibody test, or&#xD;
             human immunodeficiency&#xD;
&#xD;
          7. Major complications of lung disease (including massive hemoptysis, pneumothorax, or&#xD;
             pleural effusion) within 4 weeks prior to screening.&#xD;
&#xD;
          8. Pregnancy or breast-feeding.&#xD;
&#xD;
          9. Current smoker or a smoking history of ≥10 pack-years (number of cigarette packs/day ×&#xD;
             number of years smoked).&#xD;
&#xD;
         10. Prior or ongoing medical condition (eg, renal failure, alcoholism, drug abuse,&#xD;
             psychiatric condition), medical history, physical findings, ECG findings, or&#xD;
             laboratory abnormality that, in the investigator's opinion, could adversely affect the&#xD;
             safety of the subject, makes it unlikely that the course of treatment or follow-up&#xD;
             would be completed, or could impair the assessment of study results.&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven M Rowe, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alabama at Birmingham</affiliation>
  </overall_official>
  <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_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>August 18, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <results_first_submitted>August 7, 2018</results_first_submitted>
  <results_first_submitted_qc>June 24, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">July 19, 2019</results_first_posted>
  <last_update_submitted>June 24, 2019</last_update_submitted>
  <last_update_submitted_qc>June 24, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Alabama at Birmingham</investigator_affiliation>
    <investigator_full_name>Steven M Rowe</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ivacaftor</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 1, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/99/NCT03256799/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>N of 1 trial</recruitment_details>
      <pre_assignment_details>there was no multiple arms in this study and no multiple groups</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Ivacaftor/Ataluren</title>
          <description>the combination treatment of Ivacaftor/Ataluren were to be given over a 48 week period</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </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>Ivacaftor/Ataluren</title>
          <description>Ivacaftor/Ataluren</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
          </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <description>Caucasian, non-hispanic</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>caucasian, non-hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Lung Function</title>
        <description>change in lung function as measured by spirometry</description>
        <time_frame>Baseline through 48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ivacaftor/Ataluren</title>
            <description>Ivacaftor/Ataluren combination therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Lung Function</title>
          <description>change in lung function as measured by spirometry</description>
          <units>Liters</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>4 months from March 2017 through July 2017</time_frame>
      <desc>two pulmonary exacerbations during the N-of-1 trial, both of which occurred following cessation of combination therapy</desc>
      <group_list>
        <group group_id="E1">
          <title>Ivacaftor/Ataluren</title>
          <description>Ivacaftor/Ataluren</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="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>pulmonary exacerbation</sub_title>
                <description>two pulmonary exacerbations during the N-of-1 trial, both of which occurred following cessation of combination therapy, potentially implicating</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Steven M. Rowe</name_or_title>
      <organization>UAB</organization>
      <phone>205-975-9776</phone>
      <email>smrowe@uab.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/NCT03256799
org study id: F161208009
nct id: NCT03256799
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to explore the combination of Ataluren and ivacaftor as a
      treatment for patients with a specific cystic fibrosis mutation
In about 10% of patients with CF, the defect in the gene is known as a stop mutation. This
      mutation truncates the cystic fibrosis transductive regulator (CFTR) protein production by
      introducing a premature stop in the messenger RNA (mRNA), this type of mutation is known as a
      stop mutation. Ataluren is a novel, oral drug that promotes this gene to work effectively and
      readthrough that premature "stop sign". It is hypothesized that ivacaftor may increase the
      efficacy of Ataluren by activating a specific protein that may not be functioning properly.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Lung Function
time frame: Baseline through 48 weeks
description: change in lung function as measured by spirometry
arm group label: Ivacaftor/Ataluren
arm group type: Experimental
intervention type: Drug
intervention name: Ivacaftor/Ataluren
description: Both drugs were given in combination for 48 week study period
arm group label: Ivacaftor/Ataluren
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Steven M Rowe, MD
role: Principal Investigator
affiliation: University of Alabama at Birmingham
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Alabama at Birmingham
investigator full name: Steven M Rowe
investigator title: Principal Investigator
mesh term: Cystic Fibrosis
mesh term: Fibrosis
mesh term: Ivacaftor
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 