<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/NCT04480086</url>
  </required_header>
  <id_info>
    <org_study_id>M20-248</org_study_id>
    <secondary_id>2020-001226-65</secondary_id>
    <nct_id>NCT04480086</nct_id>
  </id_info>
  <brief_title>Safety and Tolerability Study of Mivebresib Tablet Alone or in Combination With Ruxolitinib Tablet or Navitoclax Tablet in Adult Participants With Myelofibrosis</brief_title>
  <official_title>A Phase 1b Study of Mivebresib Alone or in Combination With Ruxolitinib or Navitoclax in Subjects With Myelofibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AbbVie</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AbbVie</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Myelofibrosis (MF) is a bone marrow illness that affects blood-forming tissues in the body.&#xD;
      MF disturbs the body's normal production of blood cells, causing extensive scarring in the&#xD;
      bone marrow. This leads to severe anemia, weakness, fatigue, and an enlarged spleen. The&#xD;
      purpose of this study is to see how safe and tolerable mivebresib is, when given alone, and&#xD;
      in combination with navitoclax or ruxolitinib, for adult participants with MF.&#xD;
&#xD;
      Mivebresib is an investigational drug being developed for the treatment of MF. The study has&#xD;
      4 segments - A, B, C, and D. In Segment A, the safe dosing regimen of mivebresib is&#xD;
      identified, and then given alone as monotherapy. In Segment B, C, and D, combination&#xD;
      therapies of mivebresib with either ruxolitinib or navitoclax are given. Adult participants&#xD;
      with a diagnosis of MF will be enrolled. Around 130 participants will be enrolled in 60 sites&#xD;
      worldwide.&#xD;
&#xD;
      In Segment A, participants will receive different doses and schedules of oral mivebresib&#xD;
      tablet to identify a safe dosing regimen. Additional participants will be enrolled at the&#xD;
      identified monotherapy dosing regimen. In Segment B, participants will receive oral&#xD;
      ruxolitinib and mivebresib will be given as &quot;add-on&quot; therapy. In Segment C, participants will&#xD;
      receive mivebresib and oral navitoclax. In Segment D, participants will receive mivebresib&#xD;
      and ruxolitinib. Participants will receive treatment until disease progression or the&#xD;
      participants are not able to tolerate the study drugs.&#xD;
&#xD;
      There may be higher treatment burden for participants in this trial compared to their&#xD;
      standard of care. Participants will attend regular visits during the study at a hospital or&#xD;
      clinic. The effect of treatment will be checked by medical assessments, blood and bone marrow&#xD;
      tests, checking for side effects, and completing questionnaires.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Strategic considerations&#xD;
  </why_stopped>
  <start_date type="Actual">March 17, 2021</start_date>
  <completion_date type="Actual">July 28, 2023</completion_date>
  <primary_completion_date type="Actual">July 28, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Adverse Events</measure>
    <time_frame>Up To Approximately 1 year from start of study</time_frame>
    <description>An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. The investigator assesses the relationship of each event to the use of study drug.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants who Achieve Spleen Volume Reduction of 35% or Greater (SVR35)</measure>
    <time_frame>Up To Week 24</time_frame>
    <description>Reduction in spleen volume is measured by magnetic resonance imaging (MRI).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of Mivebresib</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>Maximum observed plasma concentration (Cmax) of Mivebresib.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Cmax (Tmax) of Mivebresib</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>The amount of time taken to reach Cmax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under Concentration vs Time Curve (AUC) of Mivebresib</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>AUC of Mivebresib will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-Life (t1/2) of Mivebresib</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>Half-life of Mivebresib will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation Ratio of Mivebresib</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>Pharmacokinetic parameters will include accumulation ratio of Mivebresib.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Clearance (CL/F) of Mivebresib</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>CL/F of Mivebresib will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution (Vd/F) of Mivebresib</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>Vd/F of mivebresib will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With &gt;= 50% Reduction in Total Symptom Score (TSS)</measure>
    <time_frame>Week 24</time_frame>
    <description>TSS is assessed using the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0. MFSAF v4.0 measures the burden of myelofibrosis-related symptoms. The symptoms are assessed on a 11-point numeric rating scale (NRS) anchored from 0 (absent) to 10 (worst imaginable).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Week 24</time_frame>
    <description>ORR is defined as the sum of rates of complete remission (CR) and partial remission (PR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of Navitoclax</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>Maximum Observed Plasma Concentration (Cmax) Of Navitoclax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Cmax (Tmax) of Navitoclax</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>The amount of time taken to reach Cmax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under Concentration vs Time Curve (AUC) of Navitoclax</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>AUC of Navitoclax will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>Maximum Observed Plasma Concentration (Cmax) Of Ruxolitinib.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Cmax (Tmax) of Ruxolitinib</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>The amount of time taken to reach Cmax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under Concentration vs Time Curve (AUC) of Ruxolitinib</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>AUC of Ruxolitinib will be calculated.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Myelofibrosis (MF)</condition>
  <arm_group>
    <arm_group_label>Segment A: Mivebresib Dose Identification and Optimization</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who have been previously treated with Janus Kinase inhibitor(s) (JAKi) and stopped such therapy, will receive different dosing regimens and schedules of mivebresib to identify the safe dosing regimen and schedule.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Segment A: Mivebresib Monotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive the identified safe dosing regimen of mivebresib as monotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Segment B: Ruxolitinib + Mivebresib &quot;Add-on&quot; Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants whose disease (myelofibrosis) is inadequately controlled by ongoing ruxolitinib therapy will receive ruxolitinib and mivebresib as &quot;add-on&quot; therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Segment C: Mivebresib + Navitoclax</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who have previously been exposed to JAKi, and stopped such therapy, will receive mivebresib and navitoclax.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Segment D: Mivebresib + Ruxolitinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who have never received JAKi will receive mivebresib and ruxolitinib.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mivebresib</intervention_name>
    <description>Tablet: Oral</description>
    <arm_group_label>Segment A: Mivebresib Dose Identification and Optimization</arm_group_label>
    <arm_group_label>Segment A: Mivebresib Monotherapy</arm_group_label>
    <arm_group_label>Segment B: Ruxolitinib + Mivebresib &quot;Add-on&quot; Therapy</arm_group_label>
    <arm_group_label>Segment C: Mivebresib + Navitoclax</arm_group_label>
    <arm_group_label>Segment D: Mivebresib + Ruxolitinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Navitoclax</intervention_name>
    <description>Tablet; Oral</description>
    <arm_group_label>Segment C: Mivebresib + Navitoclax</arm_group_label>
    <other_name>ABT-263</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ruxolitinib</intervention_name>
    <description>Tablet; Oral</description>
    <arm_group_label>Segment B: Ruxolitinib + Mivebresib &quot;Add-on&quot; Therapy</arm_group_label>
    <arm_group_label>Segment D: Mivebresib + Ruxolitinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Laboratory values indicative of adequate bone marrow, renal, and hepatic function&#xD;
             meeting protocol criteria&#xD;
&#xD;
          -  Completion of the Myelofibrosis System Assessment Form (MFSAF) on at least 4 out of&#xD;
             the 7 days prior to Day 1 with at least 2 symptoms with a score &gt;=3 or a total score&#xD;
             of &gt;=10.&#xD;
&#xD;
          -  Documented diagnosis of intermediate or high-risk primary myelofibrosis (PMF),&#xD;
             post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocytopenia&#xD;
             myelofibrosis (PET-MF) as defined by World Health Organization (WHO).&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.&#xD;
&#xD;
          -  Intermediate - 2, or High-Risk disease as defined by the Dynamic International&#xD;
             Prognostic Scoring System (For Segment A only, Intermediate - 1 with palpable&#xD;
             splenomegaly &gt;=5 centimeters [cm] below costal margin are also eligible).&#xD;
&#xD;
          -  Splenomegaly defined as spleen palpation measurement &gt;= 5 centimeters (cm) below&#xD;
             costal margin or spleen volume &gt;= 450 cubic cms as assessed by Magnetic Resonance&#xD;
             Imaging (MRI) or Computed Tomography (CT) scan (for Segments A and c, baseline spleen&#xD;
             assessment must be obtained &gt; 7 days after discontinuation of most recent&#xD;
             Myelofibrosis (MF) therapy. If possible, this assessment should occur within 10 days&#xD;
             of Cycle 1 Day 1).&#xD;
&#xD;
        Segment-Specific Prior Therapy Criteria:&#xD;
&#xD;
          -  Segment A:&#xD;
&#xD;
             --Prior exposure to one or more Janus Kinase Inhibitors (JAKi), the most recent of&#xD;
             which was discontinued &gt; 28 days prior to Cycle 1 Day 1.&#xD;
&#xD;
          -  Segment B:&#xD;
&#xD;
               -  Currently receiving ruxolitinib; AND&#xD;
&#xD;
               -  Willingness to reduce dose (if on a higher dose); and on a stable dose for 14&#xD;
                  days or longer prior to Cycle 1 Day 1; AND&#xD;
&#xD;
               -  At least one of the following criteria (a, b, or c):&#xD;
&#xD;
                    1. &gt;= 24 weeks duration of current ruxolitinib course, with evidence of disease&#xD;
                       that is resistant, refractory, or has lost response to ruxolitinib&#xD;
                       monotherapy;&#xD;
&#xD;
                    2. &lt; 24 weeks duration of current ruxolitinib course with documented disease&#xD;
                       progression as defined by any of the following:&#xD;
&#xD;
                         -  Appearance of new splenomegaly that is palpable to at least 5&#xD;
                            centimeters (cm) below the left costal margin (LCM), in participants&#xD;
                            with no evidence of splenomegaly prior to the initiation of&#xD;
                            ruxolitinib.&#xD;
&#xD;
                              -  100% increase in the palpable distance below the LCM, in&#xD;
                                 participants with measurable spleen distance 5 - 10 cm prior to&#xD;
                                 the initiation of ruxolitinib.&#xD;
&#xD;
                              -  50% increase in the palpable distance below the LCM, in&#xD;
                                 participants with measurable spleen &gt; 10 cm prior to the&#xD;
                                 initiation of ruxolitinib.&#xD;
&#xD;
                         -  A spleen volume increase &gt;= 25% (as assessed by MRI or CT) in&#xD;
                            participants with a spleen volume assessment available prior to the&#xD;
                            initiation of ruxolitinib.&#xD;
&#xD;
                    3. Prior treatment with ruxolitinib for &gt;= 28 days complicated by any of the&#xD;
                       following:&#xD;
&#xD;
                         -  Development of red blood cell transfusion requirement (at least 2&#xD;
                            units/month for 2 months).&#xD;
&#xD;
                         -  Grade &gt;= 3 adverse events of neutropenia and/or anemia while on&#xD;
                            ruxolitinib treatment, with improvement or resolution upon dose&#xD;
                            reduction.&#xD;
&#xD;
          -  Segment C:&#xD;
&#xD;
               -  Prior exposure to one or more JAKi (the most recent of which was discontinued &gt;&#xD;
                  28 days prior to Cycle 1 Day 1), and are intolerant, resistant, refractory or&#xD;
                  lost response to teh JAKi.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Segment-Specific Prior Therapy Criteria:&#xD;
&#xD;
          -  Segment A:&#xD;
&#xD;
             --Prior exposure to one or more Bromodomain and Extra Terminal (BET) inhibitors.&#xD;
&#xD;
          -  Segment B:&#xD;
&#xD;
             --Prior exposure to one or more BET inhibitors.&#xD;
&#xD;
          -  Segment C:&#xD;
&#xD;
             --Prior exposure to one or more BET inhibitors and/or any B-Cell Lymphoma 2 (BCL2)&#xD;
             and/or B-Cell Lymphoma XL (BCLXL) inhibitor, including navitoclax.&#xD;
&#xD;
          -  Segment D:&#xD;
&#xD;
               -  Prior exposure to JAKi and/or any BET inhibitor.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>ABBVIE INC.</last_name>
    <role>Study Director</role>
    <affiliation>AbbVie</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stony Brook University Hospital /ID# 222653</name>
      <address>
        <city>Stony Brook</city>
        <state>New York</state>
        <zip>11794-8183</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC Health - Cincinnati /ID# 224079</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267-2800</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thompson Cancer Survival Ctr /ID# 225802</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37916</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas MD Anderson Cancer Center /ID# 221652</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inje University Busan Paik Hospital /ID# 224043</name>
      <address>
        <city>Busan</city>
        <zip>47392</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wits Clinical Research , Wits Health Consortium (PTY) Ltd /ID# 222669</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <zip>2193</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alberts Cellular Therapy /ID# 222667</name>
      <address>
        <city>Pretoria</city>
        <state>Gauteng</state>
        <zip>0044</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
    <country>South Africa</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Brazil</country>
    <country>Bulgaria</country>
    <country>Chile</country>
    <country>Netherlands</country>
    <country>New Zealand</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
  </removed_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>August 25, 2023</last_update_submitted>
  <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>mivebresib</keyword>
  <keyword>Navitoclax</keyword>
  <keyword>Ruxolitinib</keyword>
  <keyword>ABT-263</keyword>
  <keyword>Cancer</keyword>
  <keyword>Myelofibrosis</keyword>
  <keyword>MF</keyword>
  <keyword>ABBV-075</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Primary Myelofibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Navitoclax</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04480086
org study id: M20-248
secondary id: 2020-001226-65
nct id: NCT04480086
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Myelofibrosis (MF) is a bone marrow illness that affects blood-forming tissues in the body.
      MF disturbs the body's normal production of blood cells, causing extensive scarring in the
      bone marrow. This leads to severe anemia, weakness, fatigue, and an enlarged spleen. The
      purpose of this study is to see how safe and tolerable mivebresib is, when given alone, and
      in combination with navitoclax or ruxolitinib, for adult participants with MF.

      Mivebresib is an investigational drug being developed for the treatment of MF. The study has
      4 segments - A, B, C, and D. In Segment A, the safe dosing regimen of mivebresib is
      identified, and then given alone as monotherapy. In Segment B, C, and D, combination
      therapies of mivebresib with either ruxolitinib or navitoclax are given. Adult participants
      with a diagnosis of MF will be enrolled. Around 130 participants will be enrolled in 60 sites
      worldwide.

      In Segment A, participants will receive different doses and schedules of oral mivebresib
      tablet to identify a safe dosing regimen. Additional participants will be enrolled at the
      identified monotherapy dosing regimen. In Segment B, participants will receive oral
      ruxolitinib and mivebresib will be given as "add-on" therapy. In Segment C, participants will
      receive mivebresib and oral navitoclax. In Segment D, participants will receive mivebresib
      and ruxolitinib. Participants will receive treatment until disease progression or the
      participants are not able to tolerate the study drugs.

      There may be higher treatment burden for participants in this trial compared to their
      standard of care. Participants will attend regular visits during the study at a hospital or
      clinic. The effect of treatment will be checked by medical assessments, blood and bone marrow
      tests, checking for side effects, and completing questionnaires.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Adverse Events
time frame: Up To Approximately 1 year from start of study
description: An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. The investigator assesses the relationship of each event to the use of study drug.
measure: Percentage of Participants who Achieve Spleen Volume Reduction of 35% or Greater (SVR35)
time frame: Up To Week 24
description: Reduction in spleen volume is measured by magnetic resonance imaging (MRI).
measure: Maximum Observed Plasma Concentration (Cmax) of Mivebresib
time frame: Up To Week 12
description: Maximum observed plasma concentration (Cmax) of Mivebresib.
measure: Time to Cmax (Tmax) of Mivebresib
time frame: Up To Week 12
description: The amount of time taken to reach Cmax.
measure: Area Under Concentration vs Time Curve (AUC) of Mivebresib
time frame: Up To Week 12
description: AUC of Mivebresib will be calculated.
measure: Half-Life (t1/2) of Mivebresib
time frame: Up To Week 12
description: Half-life of Mivebresib will be calculated.
measure: Accumulation Ratio of Mivebresib
time frame: Up To Week 12
description: Pharmacokinetic parameters will include accumulation ratio of Mivebresib.
measure: Apparent Clearance (CL/F) of Mivebresib
time frame: Up To Week 12
description: CL/F of Mivebresib will be calculated.
measure: Apparent Volume of Distribution (Vd/F) of Mivebresib
time frame: Up To Week 12
description: Vd/F of mivebresib will be calculated.
measure: Percentage of Participants With >= 50% Reduction in Total Symptom Score (TSS)
time frame: Week 24
description: TSS is assessed using the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0. MFSAF v4.0 measures the burden of myelofibrosis-related symptoms. The symptoms are assessed on a 11-point numeric rating scale (NRS) anchored from 0 (absent) to 10 (worst imaginable).
measure: Objective Response Rate (ORR)
time frame: Week 24
description: ORR is defined as the sum of rates of complete remission (CR) and partial remission (PR).
measure: Maximum Observed Plasma Concentration (Cmax) of Navitoclax
time frame: Up To Week 12
description: Maximum Observed Plasma Concentration (Cmax) Of Navitoclax.
measure: Time to Cmax (Tmax) of Navitoclax
time frame: Up To Week 12
description: The amount of time taken to reach Cmax.
measure: Area Under Concentration vs Time Curve (AUC) of Navitoclax
time frame: Up To Week 12
description: AUC of Navitoclax will be calculated.
measure: Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib
time frame: Up To Week 12
description: Maximum Observed Plasma Concentration (Cmax) Of Ruxolitinib.
measure: Time to Cmax (Tmax) of Ruxolitinib
time frame: Up To Week 12
description: The amount of time taken to reach Cmax.
measure: Area Under Concentration vs Time Curve (AUC) of Ruxolitinib
time frame: Up To Week 12
description: AUC of Ruxolitinib will be calculated.
arm group label: Segment A: Mivebresib Dose Identification and Optimization
arm group type: Experimental
description: Participants who have been previously treated with Janus Kinase inhibitor(s) (JAKi) and stopped such therapy, will receive different dosing regimens and schedules of mivebresib to identify the safe dosing regimen and schedule.
arm group label: Segment A: Mivebresib Monotherapy
arm group type: Experimental
description: Participants will receive the identified safe dosing regimen of mivebresib as monotherapy.
arm group label: Segment B: Ruxolitinib + Mivebresib "Add-on" Therapy
arm group type: Experimental
description: Participants whose disease (myelofibrosis) is inadequately controlled by ongoing ruxolitinib therapy will receive ruxolitinib and mivebresib as "add-on" therapy.
arm group label: Segment C: Mivebresib + Navitoclax
arm group type: Experimental
description: Participants who have previously been exposed to JAKi, and stopped such therapy, will receive mivebresib and navitoclax.
arm group label: Segment D: Mivebresib + Ruxolitinib
arm group type: Experimental
description: Participants who have never received JAKi will receive mivebresib and ruxolitinib.
intervention type: Drug
intervention name: Mivebresib
description: Tablet: Oral
arm group label: Segment A: Mivebresib Dose Identification and Optimization
arm group label: Segment A: Mivebresib Monotherapy
arm group label: Segment B: Ruxolitinib + Mivebresib "Add-on" Therapy
arm group label: Segment C: Mivebresib + Navitoclax
arm group label: Segment D: Mivebresib + Ruxolitinib
intervention type: Drug
intervention name: Navitoclax
description: Tablet; Oral
arm group label: Segment C: Mivebresib + Navitoclax
other name: ABT-263
intervention type: Drug
intervention name: Ruxolitinib
description: Tablet; Oral
arm group label: Segment B: Ruxolitinib + Mivebresib "Add-on" Therapy
arm group label: Segment D: Mivebresib + Ruxolitinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: ABBVIE INC.
role: Study Director
affiliation: AbbVie
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Korea, Republic of
country: South Africa
country: United States
country: Argentina
country: Australia
country: Brazil
country: Bulgaria
country: Chile
country: Netherlands
country: New Zealand
country: Turkey
country: United Kingdom
responsible party type: Sponsor
mesh term: Primary Myelofibrosis
mesh term: Navitoclax
sharing ipd: No