<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/NCT04477850</url>
  </required_header>
  <id_info>
    <org_study_id>ACE-536-MDS-004</org_study_id>
    <secondary_id>U1111-1251-9249</secondary_id>
    <nct_id>NCT04477850</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Efficacy, Drug Levels and Safety of Luspatercept (ACE-536) for the Treatment of Anemia Due to IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes in Chinese and Japanese Participants With Ring Sideroblasts Who Require Red Blood Cell Transfusions</brief_title>
  <official_title>A Phase 2, Multicenter, Single-Arm Bridging Study to Evaluate the Efficacy, Pharmacokinetics, and Safety of Luspatercept (ACE-536) for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Myelodysplastic Syndromes(MDS) in Chinese and Japanese Subjects With Ring Sideroblasts Who Require Red Blood Cell Transfusions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Celgene</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Celgene</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy and safety of luspatercept (ACE-536)&#xD;
      for the treatment of anemia due to Revised International Prognostic Scoring System (IPSS-R)&#xD;
      very low, low, or intermediate risk myelodysplastic syndromes (MDS) in Chinese and Japanese&#xD;
      participants with ring sideroblasts who require Red Blood Cells (RBC) transfusions.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 30, 2020</start_date>
  <completion_date type="Anticipated">February 23, 2026</completion_date>
  <primary_completion_date type="Anticipated">August 26, 2023</primary_completion_date>
  <phase>Phase 2</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>Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 weeks</measure>
    <time_frame>Week 1 through Week 24</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>RBC-TI ≥ 12 weeks</measure>
    <time_frame>Week 1 through Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in Red Blood Cell (RBC) units transfused over 16 weeks compared to baseline</measure>
    <time_frame>Week 9 through Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified hematologic improvement - erythroid (mHI-E) per International Working Group (IWG)</measure>
    <time_frame>Week 1 through Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean hemoglobin increase ≥ 1.0 g/dL</measure>
    <time_frame>Week 1 through Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of RBC-TI</measure>
    <time_frame>Week 1 through Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean decrease in serum ferritin compared to baseline</measure>
    <time_frame>Week 9 through Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean decrease in iron chelation therapy (ICT) use compared to baseline</measure>
    <time_frame>Week 9 through Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to RBC-TI</measure>
    <time_frame>Week 1 through Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression to acute myeloid leukemia (AML)</measure>
    <time_frame>Cycle1 Day1 (each cycle is 21 days) through at least 3 years post first dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Cycle1 Day1 (each cycle is 21 days) through at least 3 years post first dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of type of adverse events (AEs)</measure>
    <time_frame>Screening through 42 days post last dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of frequency of AEs</measure>
    <time_frame>Screening through 42 days post last dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of severity of AEs</measure>
    <time_frame>Screening through 42 days post last dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of seriousness of AEs</measure>
    <time_frame>Screening through 42 days post last dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of relationship of AEs to study treatment</measure>
    <time_frame>Screening through 42 days post last dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics - Area under the curve (AUC)</measure>
    <time_frame>Cycle1 Day1 (each cycle is 21 days) through 1-year post first dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics - Maximum plasma concentration of the drug (Cmax)</measure>
    <time_frame>Cycle1 Day1 (each cycle is 21 days) through 1-year post first dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of Anti-drug antibodies (ADA)</measure>
    <time_frame>Cycle1 Day1 (each cycle is 21 days) through 1-year post first dose</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Myelodysplastic Syndromes</condition>
  <arm_group>
    <arm_group_label>Luspatercept Administration</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Luspatercept</intervention_name>
    <description>Specified dose on specified days</description>
    <arm_group_label>Luspatercept Administration</arm_group_label>
    <other_name>ACE-536</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Refractory or intolerant to, or ineligible for, prior Erythropoiesis stimulating agent&#xD;
             (ESA) treatment as defined by any one of the following: Refractory to prior ESA&#xD;
             treatment, Intolerant to prior ESA treatment, or ESA ineligible.&#xD;
&#xD;
          -  previously treated with an ESA or granulocyte colony-stimulating factor,&#xD;
             granulocyte-macrophage colony-stimulating factor, both agents must have been&#xD;
             discontinued ≥ 4 weeks prior to date of luspatercept treatment&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior therapy with disease modifying agents for underlying MDS disease&#xD;
&#xD;
          -  Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies,&#xD;
             or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding&#xD;
&#xD;
          -  Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) or&#xD;
             alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) ≥ 3.0 x upper&#xD;
             limit of normal (ULN)&#xD;
&#xD;
        Other protocol-defined inclusion/exclusion criteria apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bristol-Myers Squibb</last_name>
    <role>Study Director</role>
    <affiliation>Bristol-Myers Squibb</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Local Institution - 100</name>
      <address>
        <city>Beijing</city>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 107</name>
      <address>
        <city>Chengdu, Sichuan</city>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 105</name>
      <address>
        <city>Guangzhou</city>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 103</name>
      <address>
        <city>Guangzhou</city>
        <zip>510080</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 109</name>
      <address>
        <city>Guangzhou</city>
        <zip>510515</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 102</name>
      <address>
        <city>Hangzhou City</city>
        <zip>310006</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 112</name>
      <address>
        <city>Nanchang</city>
        <zip>330006</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 108</name>
      <address>
        <city>Nanjing</city>
        <zip>210029</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 114</name>
      <address>
        <city>Shanghai</city>
        <zip>0</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 101</name>
      <address>
        <city>Shanghai</city>
        <zip>200233</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 104</name>
      <address>
        <city>Suzhu</city>
        <zip>215006</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 106</name>
      <address>
        <city>Tianjin</city>
        <zip>300020</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 111</name>
      <address>
        <city>Wenzhou</city>
        <zip>325000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 110</name>
      <address>
        <city>Wuhan</city>
        <zip>430022</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 209</name>
      <address>
        <city>Matsuyama</city>
        <state>Ehime</state>
        <zip>790-8524</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 203</name>
      <address>
        <city>Nagasaki-shi</city>
        <state>Nagasaki</state>
        <zip>852-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 210</name>
      <address>
        <city>Osakasayama</city>
        <state>Osaka</state>
        <zip>5898511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 206</name>
      <address>
        <city>Kamogawa</city>
        <zip>296-8602</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 201</name>
      <address>
        <city>Mibu-Machi</city>
        <zip>321-0293</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 208</name>
      <address>
        <city>Ogaki</city>
        <zip>503-8502</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 205</name>
      <address>
        <city>Osaka</city>
        <zip>545-8585</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 204</name>
      <address>
        <city>Sagamihara</city>
        <zip>252-0375</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 207</name>
      <address>
        <city>Sendai</city>
        <zip>980-8574</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 202</name>
      <address>
        <city>Shinagawa-ku, Tokyo</city>
        <zip>141-8625</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
    <country>Japan</country>
  </location_countries>
  <link>
    <url>https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html</url>
    <description>BMS Clinical Trial Information</description>
  </link>
  <link>
    <url>https://www.bmsstudyconnect.com/s/US/English/USenHome</url>
    <description>BMS Clinical Trial Patient Recruiting</description>
  </link>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>May 1, 2023</last_update_submitted>
  <last_update_submitted_qc>May 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Myelodysplastic Syndromes</keyword>
  <keyword>MDS</keyword>
  <keyword>ACE-536</keyword>
  <keyword>Anemia</keyword>
  <keyword>Luspatercept</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Anemia</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Luspatercept</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Information relating to our policy on data sharing and the process for requesting data can be found at the following link:&#xD;
https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>See Plan Description</ipd_time_frame>
    <ipd_access_criteria>See Plan Description</ipd_access_criteria>
    <ipd_url>https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/</ipd_url>
  </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/NCT04477850
org study id: ACE-536-MDS-004
secondary id: U1111-1251-9249
nct id: NCT04477850
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the efficacy and safety of luspatercept (ACE-536)
      for the treatment of anemia due to Revised International Prognostic Scoring System (IPSS-R)
      very low, low, or intermediate risk myelodysplastic syndromes (MDS) in Chinese and Japanese
      participants with ring sideroblasts who require Red Blood Cells (RBC) transfusions.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 weeks
time frame: Week 1 through Week 24
measure: RBC-TI ≥ 12 weeks
time frame: Week 1 through Week 24
measure: Reduction in Red Blood Cell (RBC) units transfused over 16 weeks compared to baseline
time frame: Week 9 through Week 24
measure: Modified hematologic improvement - erythroid (mHI-E) per International Working Group (IWG)
time frame: Week 1 through Week 24
measure: Mean hemoglobin increase ≥ 1.0 g/dL
time frame: Week 1 through Week 24
measure: Duration of RBC-TI
time frame: Week 1 through Week 24
measure: Mean decrease in serum ferritin compared to baseline
time frame: Week 9 through Week 24
measure: Mean decrease in iron chelation therapy (ICT) use compared to baseline
time frame: Week 9 through Week 24
measure: Time to RBC-TI
time frame: Week 1 through Week 24
measure: Progression to acute myeloid leukemia (AML)
time frame: Cycle1 Day1 (each cycle is 21 days) through at least 3 years post first dose
measure: Overall survival (OS)
time frame: Cycle1 Day1 (each cycle is 21 days) through at least 3 years post first dose
measure: Incidence of type of adverse events (AEs)
time frame: Screening through 42 days post last dose
measure: Incidence of frequency of AEs
time frame: Screening through 42 days post last dose
measure: Incidence of severity of AEs
time frame: Screening through 42 days post last dose
measure: Incidence of seriousness of AEs
time frame: Screening through 42 days post last dose
measure: Incidence of relationship of AEs to study treatment
time frame: Screening through 42 days post last dose
measure: Pharmacokinetics - Area under the curve (AUC)
time frame: Cycle1 Day1 (each cycle is 21 days) through 1-year post first dose
measure: Pharmacokinetics - Maximum plasma concentration of the drug (Cmax)
time frame: Cycle1 Day1 (each cycle is 21 days) through 1-year post first dose
measure: Frequency of Anti-drug antibodies (ADA)
time frame: Cycle1 Day1 (each cycle is 21 days) through 1-year post first dose
arm group label: Luspatercept Administration
arm group type: Experimental
intervention type: Drug
intervention name: Luspatercept
description: Specified dose on specified days
arm group label: Luspatercept Administration
other name: ACE-536
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Bristol-Myers Squibb
role: Study Director
affiliation: Bristol-Myers Squibb
facility: 
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country: China
country: Japan
url: https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
description: BMS Clinical Trial Information
url: https://www.bmsstudyconnect.com/s/US/English/USenHome
description: BMS Clinical Trial Patient Recruiting
responsible party type: Sponsor
mesh term: Preleukemia
mesh term: Anemia
mesh term: Myelodysplastic Syndromes
mesh term: Syndrome
mesh term: Luspatercept
sharing ipd: Yes
ipd description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link:
https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: See Plan Description
ipd access criteria: See Plan Description
ipd url: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/