<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/NCT04400487</url>
  </required_header>
  <id_info>
    <org_study_id>GBT440-039</org_study_id>
    <secondary_id>C5341024</secondary_id>
    <nct_id>NCT04400487</nct_id>
  </id_info>
  <brief_title>Actigraphy Improvement With Voxelotor (ActIVe) Study</brief_title>
  <acronym>ActIVe</acronym>
  <official_title>A Phase 4, Multicenter, Open-label Study to Evaluate the Treatment Effect of Voxelotor on Physical Activity in Adolescents and Adults With Sickle Cell Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a study to evaluate the effect of voxelotor on daily physical activity and sleep&#xD;
      quality, as measured by a wrist-worn device in participants with sickle cell disease (SCD)&#xD;
      and chronic moderate anemia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      All participants will receive Voxelotor as treatment. There will be approximately 13 sites in&#xD;
      the US.&#xD;
&#xD;
      Participant safety and tolerability will be monitored during the study using standard&#xD;
      measures, including physical examinations, vital signs (including temperature, blood&#xD;
      pressure, pulse rate, respiratory rate and peripheral oxygen saturation [SpO2]), clinical&#xD;
      laboratory tests, and adverse event (AE) monitoring.&#xD;
&#xD;
      Screening Period (up to 4 weeks in duration): During this period, participants will sign the&#xD;
      informed consent form (ICF), after which they will complete the screening assessments as&#xD;
      detailed in the Schedule of Assessments (SOA).&#xD;
&#xD;
      Run-in Period (2 weeks in duration): During this period, participants will enter a 2-week&#xD;
      run-in period (Day -14 to Day -1) during which baseline actigraphy measures of physical&#xD;
      activity and sleep quality, overnight pulse oximetry assessments of oxygen saturation, and&#xD;
      Patient-Reported Outcome (PRO) assessments will be collected before initiating treatment with&#xD;
      voxelotor.&#xD;
&#xD;
      Treatment Period (24 weeks in duration): After completion of the 14-day Run-in Period,&#xD;
      participants will enter the open label treatment period and receive voxelotor 1500 mg once&#xD;
      daily for 24 weeks. Repeat actigraphy assessments of physical activity and sleep quality, and&#xD;
      overnight pulse oximetry will be performed during the treatment period (Weeks 10 to 12 and&#xD;
      Weeks 22 to 24). PRO and Clinical Global Impression (CGI) assessments will be completed at&#xD;
      scheduled study visits. The open-label treatment period is considered the continuous 24 weeks&#xD;
      of voxelotor treatment from date of first dose (Day 1).&#xD;
&#xD;
      Follow-up Period (4 weeks in duration): Immediately following the 24-week treatment period,&#xD;
      participants will enter a 4-week Follow-up Period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 23, 2020</start_date>
  <completion_date type="Actual">September 18, 2022</completion_date>
  <primary_completion_date type="Actual">September 18, 2022</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>Change in total daily physical activity</measure>
    <time_frame>Baseline, Week 10-12, Week 22-24</time_frame>
    <description>Change in total daily physical activity (expressed in counts per minute)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in total nocturnal sleep time</measure>
    <time_frame>Baseline, Week 10-12, Week 22-24</time_frame>
    <description>Change in total nocturnal sleep time (TST)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in wake time after sleep onset</measure>
    <time_frame>Baseline, Week 10-12, Week 22-24</time_frame>
    <description>Change in wake time after sleep onset (WASO)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in sleep efficiency</measure>
    <time_frame>Baseline, Week 10-12, Week 22-24</time_frame>
    <description>Change in sleep efficiency (SE) measured as total sleep time/time in bed</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in mean nocturnal hemoglobin oxygen saturation percentage</measure>
    <time_frame>Baseline, Week 10-12, Week 22-24</time_frame>
    <description>Change in mean overnight SpO2 percentage as measured by pulse oximetry SpO2 percent</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of participants with a &gt;1 g/dL increase in Hb</measure>
    <time_frame>Baseline, Week 10-12, Week 22-24</time_frame>
    <description>Proportion of participants with a &gt;1 g/dL increase in Hb</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in median number of overnight SpO2 dips &gt; 3% per hour</measure>
    <time_frame>Baseline, Week 10-12, Week 22-24</time_frame>
    <description>Change in median number of overnight SpO2 dips &gt; 3% per hour as measured by pulse oximetry SpO2 percent</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Sickle Cell Disease</condition>
  <condition>Sickle Cell Anemia</condition>
  <arm_group>
    <arm_group_label>Voxelotor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive voxelotor at 1500 mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Voxelotor</intervention_name>
    <description>500 mg Tablet, Oral, With or Without Food</description>
    <arm_group_label>Voxelotor</arm_group_label>
    <other_name>GBT440</other_name>
    <other_name>Oxbryta</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female participants with SCA (sickle hemoglobin with two sickle cell genes&#xD;
             [HbSS] or sickle hemoglobin (S) and one beta thalassemia gene [HbS β0] thal genotype)&#xD;
&#xD;
          2. Between 12 to 55 years of age (inclusive)&#xD;
&#xD;
          3. Screening Hb level ≤8.0 g/dL&#xD;
&#xD;
          4. Treatment with hydroxyurea (HU) therapy on study is permitted if the participant has&#xD;
             been on a stable dose for at least 90 days before enrollment with no dose&#xD;
             modifications planned or anticipated by the Investigator&#xD;
&#xD;
          5. Treatment with glutamine is permitted&#xD;
&#xD;
          6. Treatment with erythropoiesis-stimulating agents (ESAs) is permitted if the&#xD;
             participant has been on a stable dose for at least 12 weeks before enrollment with no&#xD;
             dose modifications planned or anticipated by the Investigator&#xD;
&#xD;
          7. Female participants of child-bearing potential must use highly effective methods of&#xD;
             contraception to 30 days after the last dose of study drug. Male participants must use&#xD;
             barrier methods of contraception to 30 days after the last dose of study drug&#xD;
&#xD;
          8. Females of child-bearing potential are required to have a negative pregnancy test&#xD;
             before the administration of study drug&#xD;
&#xD;
          9. Written informed consent and/or parental/guardian consent and participant assent per&#xD;
             Institutional Review Board (IRB) policy and requirements, consistent with ICH&#xD;
             guidelines&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Red blood cell (RBC transfusion within 3 months before initiation of study drug&#xD;
&#xD;
          2. Planned initiation of regularly scheduled RBC transfusion therapy (also termed&#xD;
             chronic, prophylactic, or preventive transfusion) during the study&#xD;
&#xD;
          3. Hospitalization for vaso-occlusive crisis (VOC) or acute chest syndrome (ACS) within&#xD;
             30 days prior to informed consent/assent.&#xD;
&#xD;
          4. More than 10 VOCs requiring hospitalization, emergency department or clinic visit&#xD;
             within the past 12 months&#xD;
&#xD;
          5. Planned elective surgery within the next 6 months&#xD;
&#xD;
          6. Physical inactivity attributable to clinically significant musculoskeletal,&#xD;
             cardiovascular, or respiratory comorbidities&#xD;
&#xD;
          7. Anemia due to bone marrow failure (eg, myelodysplasia)&#xD;
&#xD;
          8. Absolute reticulocyte count (ARC) &lt; 100 x10^9/L&#xD;
&#xD;
          9. Screening alanine aminotransferase (ALT) &gt; 4× upper limit of normal (ULN)&#xD;
&#xD;
         10. Severe renal dysfunction (estimated glomerular filtration rate [GFR] &lt; 30 mL/min/1.73&#xD;
             m2 by Schwartz formula) or is on chronic dialysis&#xD;
&#xD;
         11. Known active hepatitis A, B or C or known to be human immunodeficiency virus&#xD;
             (HIV)-positive.&#xD;
&#xD;
         12. Females who are breast-feeding or pregnant&#xD;
&#xD;
         13. Major surgery within 8 weeks before enrollment. Participants must have completely&#xD;
             recovered from any previous surgery before enrollment&#xD;
&#xD;
         14. History of hematopoietic stem cell transplant or gene therapy&#xD;
&#xD;
         15. Received an investigational drug within 30 days or 5-half-lives, whichever is longer,&#xD;
             prior to consent, or is currently participating in another trial of an investigational&#xD;
             or marketed drug (or medical device)&#xD;
&#xD;
         16. Use of concomitant medications (eg, crizanlizumab) that confound the ability to&#xD;
             interpret data from the study&#xD;
&#xD;
         17. Medical, psychological, or behavioral condition that, in the opinion of the&#xD;
             Investigator, would confound or interfere with evaluation of safety and/or efficacy of&#xD;
             the study drug, prevent compliance with the study protocol; preclude informed consent;&#xD;
             or, render the participant unable/unlikely to comply with the study procedures&#xD;
&#xD;
         18. Use of herbal medications (e.g., St. John's Wort), sensitive cytochrome P450 (CYP) 3A4&#xD;
             substrates with a narrow therapeutic index, strong CYP3A4 inhibitors, fluconazole, or&#xD;
             moderate or strong CYP3A4 inducers&#xD;
&#xD;
         19. Symptomatic coronavirus disease of 2019 (COVID-19) infection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pfizer CT.gov Call Center</last_name>
    <role>Study Director</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UConn Health</name>
      <address>
        <city>Farmington</city>
        <state>Connecticut</state>
        <zip>06030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Healthcare of Atlanta</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Michigan</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Children's Hospital at Montefiore</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10476</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke Department of Pediatrics</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University Wexner Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Medical Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas Health Science Center at Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VCU Health</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://pmiform.com/clinical-trial-info-request?StudyID=GBT440-039</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>March 25, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 22, 2020</study_first_posted>
  <last_update_submitted>July 18, 2023</last_update_submitted>
  <last_update_submitted_qc>July 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2023</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>Anemia, Sickle Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>September 15, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04400487
org study id: GBT440-039
secondary id: C5341024
nct id: NCT04400487
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a study to evaluate the effect of voxelotor on daily physical activity and sleep
      quality, as measured by a wrist-worn device in participants with sickle cell disease (SCD)
      and chronic moderate anemia.
All participants will receive Voxelotor as treatment. There will be approximately 13 sites in
      the US.

      Participant safety and tolerability will be monitored during the study using standard
      measures, including physical examinations, vital signs (including temperature, blood
      pressure, pulse rate, respiratory rate and peripheral oxygen saturation [SpO2]), clinical
      laboratory tests, and adverse event (AE) monitoring.

      Screening Period (up to 4 weeks in duration): During this period, participants will sign the
      informed consent form (ICF), after which they will complete the screening assessments as
      detailed in the Schedule of Assessments (SOA).

      Run-in Period (2 weeks in duration): During this period, participants will enter a 2-week
      run-in period (Day -14 to Day -1) during which baseline actigraphy measures of physical
      activity and sleep quality, overnight pulse oximetry assessments of oxygen saturation, and
      Patient-Reported Outcome (PRO) assessments will be collected before initiating treatment with
      voxelotor.

      Treatment Period (24 weeks in duration): After completion of the 14-day Run-in Period,
      participants will enter the open label treatment period and receive voxelotor 1500 mg once
      daily for 24 weeks. Repeat actigraphy assessments of physical activity and sleep quality, and
      overnight pulse oximetry will be performed during the treatment period (Weeks 10 to 12 and
      Weeks 22 to 24). PRO and Clinical Global Impression (CGI) assessments will be completed at
      scheduled study visits. The open-label treatment period is considered the continuous 24 weeks
      of voxelotor treatment from date of first dose (Day 1).

      Follow-up Period (4 weeks in duration): Immediately following the 24-week treatment period,
      participants will enter a 4-week Follow-up Period.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in total daily physical activity
time frame: Baseline, Week 10-12, Week 22-24
description: Change in total daily physical activity (expressed in counts per minute)
measure: Change in total nocturnal sleep time
time frame: Baseline, Week 10-12, Week 22-24
description: Change in total nocturnal sleep time (TST)
measure: Change in wake time after sleep onset
time frame: Baseline, Week 10-12, Week 22-24
description: Change in wake time after sleep onset (WASO)
measure: Change in sleep efficiency
time frame: Baseline, Week 10-12, Week 22-24
description: Change in sleep efficiency (SE) measured as total sleep time/time in bed
measure: Change in mean nocturnal hemoglobin oxygen saturation percentage
time frame: Baseline, Week 10-12, Week 22-24
description: Change in mean overnight SpO2 percentage as measured by pulse oximetry SpO2 percent
measure: Proportion of participants with a >1 g/dL increase in Hb
time frame: Baseline, Week 10-12, Week 22-24
description: Proportion of participants with a >1 g/dL increase in Hb
measure: Change in median number of overnight SpO2 dips > 3% per hour
time frame: Baseline, Week 10-12, Week 22-24
description: Change in median number of overnight SpO2 dips > 3% per hour as measured by pulse oximetry SpO2 percent
arm group label: Voxelotor
arm group type: Experimental
description: Participants will receive voxelotor at 1500 mg
intervention type: Drug
intervention name: Voxelotor
description: 500 mg Tablet, Oral, With or Without Food
arm group label: Voxelotor
other name: GBT440
other name: Oxbryta
criteria: 
gender: All
minimum age: 12 Years
maximum age: 55 Years
healthy volunteers: No
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://pmiform.com/clinical-trial-info-request?StudyID=GBT440-039
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: Anemia, Sickle Cell
sharing ipd: No
submitted: September 15, 2023