xml: <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/NCT06009497</url>
    </required_header>
    <id_info>
      <org_study_id>Romiplostim-1</org_study_id>
      <nct_id>NCT06009497</nct_id>
    </id_info>
    <brief_title>Romiplostim in Combination With CsA vs. CsA in the Treatment of Newly Diagnosed NSAA</brief_title>
    <official_title>Romiplostim in Combination With Ciclosporin Versus Ciclosporin in the Treatment of Newly Diagnosed Non-severe Aplastic Anemia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Peking Union Medical College Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Peking Union Medical College Hospital</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>
        Aplastic anemia (AA) is a group of clinical syndromes caused by a significant decrease in&#xD;
        bone marrow hematopoietic tissue from different etiologies, resulting in hematopoietic&#xD;
        failure. Treatment options for patients with aplastic anemia are very limited. In a phase&#xD;
        II/III, multicenter, open-label study exploring the efficacy and safety of romiplostim, the&#xD;
        primary endpoint showed an overall response rate of 84% [95% CI 66-95%] at week 27. However,&#xD;
        there are no prospective clinical data exploring whether romiplostim combined with&#xD;
        ciclosporin (CsA) can further improve efficacy than ciclosporin monotherapy in newly&#xD;
        diagnosed NSAA. Therefore, we aimed to compare the efficacy and safety of romiplostim in&#xD;
        combination with CsA versus CsA monotherapy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Aplastic anemia (AA) is a group of clinical syndromes caused by a significant decrease in&#xD;
        bone marrow hematopoietic tissue from different etiologies, resulting in hematopoietic&#xD;
        failure. Treatment options for patients with aplastic anemia are very limited. By binding to&#xD;
        the thrombopoietin (TPO) receptor, thrombopoietin receptor agonists (TPO-RAs) can cause&#xD;
        conformational changes in the TPO receptor, activate the JAK2/STATS pathway, and increase&#xD;
        megakaryocyte progenitor cells proliferation and platelet production. At present, TPO-RAs&#xD;
        including eltrombopag, lusutrombopag, romiplostim, and avatrombopag have been approved by&#xD;
        FDA. In a phase II/III, multicenter, open-label study exploring the efficacy and safety of&#xD;
        romiplostim, 31 patients with refractory AA were enrolled. The primary endpoint for the&#xD;
        proportion of patients who achieved any hematological (platelet, neutrophil, and red blood&#xD;
        cell) response at week 27 was 84% [95% CI 66-95%]. At week 53, the three-line response rate&#xD;
        was 39% (95% CI 22-58%). However, there are no prospective clinical data exploring whether&#xD;
        romiplostim combined with ciclosporin (CsA) can further improve efficacy than ciclosporin&#xD;
        monotherapy in newly diagnosed NSAA. Since romiplostim and CsA have good safety, if it is&#xD;
        proved that the combination of the two drugs is superior to ciclosporin monotherapy, it can&#xD;
        quickly improve blood patterns in NSAA, avoid the use of more expensive ATG, and provide some&#xD;
        help to reduce the economic burden of AA patients.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">December 2025</completion_date>
    <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
    <phase>Phase 4</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>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>overall response rate (ORR)</measure>
      <time_frame>3, 6 months</time_frame>
      <description>Proportion of patients who achieved complete response and partial response.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>complete response rate (CRR)</measure>
      <time_frame>3, 6 months</time_frame>
      <description>Proportion of patients who achieved complete response.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>adverse event rate</measure>
      <time_frame>3, 6 months</time_frame>
      <description>All adverse events that occur or worsen during treatment, as well as those that occur later but are believed by the investigator to be related to the investigational drug, will be reported.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">44</enrollment>
    <condition>Non Severe Aplastic Anemia</condition>
    <arm_group>
      <arm_group_label>Romiplostim+CsA</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Romiplostim 10 µg/kg, subcutaneous injection, once a week, for at least 3 months. Patients with platelet count ≥50×109/L can stop using, and continue to use with platelet count &lt; 50×109/L.&#xD;
  Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml. Ciclosporin should be used for at least 6 months to evaluate the efficacy. Effective patients will continue to use ciclosporin for at least 1.5 years, followed by a slow reduction.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>CsA</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml. Ciclosporin should be used for at least 6 months to evaluate the efficacy. Effective patients will continue to use ciclosporin for at least 1.5 years, followed by a slow reduction.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Romiplostim</intervention_name>
      <description>Romiplostim 10 µg/kg, subcutaneous injection, once a week.</description>
      <arm_group_label>Romiplostim+CsA</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Ciclosporin</intervention_name>
      <description>Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml.</description>
      <arm_group_label>CsA</arm_group_label>
      <arm_group_label>Romiplostim+CsA</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age ≥18 years old.&#xD;
  &#xD;
            2. Clearly diagnosed as untreated NSAA.&#xD;
  &#xD;
            3. At least one of the following conditions was met at the time of enrollment: hemoglobin&#xD;
               &lt;90 g/L. Platelet &lt;30×109/L, neutrophils &lt;1.0×109/L.&#xD;
  &#xD;
            4. Baseline liver and kidney function (ALT, AST, Cr) was less than 2 times the normal&#xD;
               value.&#xD;
  &#xD;
            5. No active infection; Not pregnant or breastfeeding.&#xD;
  &#xD;
            6. Agree to sign the consent form.&#xD;
  &#xD;
            7. The Eastern Cancer Collaboration Group (ECOG) score was 0-2.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Pancytopenia caused by other causes, such as myelodysplastic syndrome (MDS).&#xD;
  &#xD;
            2. There is cytogenetic evidence of clonal hematologic bone marrow diseases (MDS, AML).&#xD;
  &#xD;
            3. PNH clone ≥50%.&#xD;
  &#xD;
            4. Had received hematopoietic stem cell transplantation (HSCT) before enrollment.&#xD;
  &#xD;
            5. Immunosuppressive therapy such as ATG or cyclosporine use for more than 2 weeks.&#xD;
  &#xD;
            6. Infection or bleeding that is not controlled by standard treatment.&#xD;
  &#xD;
            7. Allergic to recombinant TPO or Hitrepopar.&#xD;
  &#xD;
            8. Active HIV, HCV, HBV infection or cirrhosis, or portal hypertension.&#xD;
  &#xD;
            9. Any concomitant malignancy or local basal cell carcinoma of the skin within 5 years.&#xD;
  &#xD;
           10. Previous history of thromboembolic events, heart attack or stroke (including&#xD;
               antiphospholipid antibody syndrome), and current use of anticoagulants.&#xD;
  &#xD;
           11. Women who are pregnant or nursing (lactation).&#xD;
  &#xD;
           12. Have participated in other clinical trials within 3 months&#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_contact>
      <last_name>Bing Han</last_name>
      <phone>13601059938</phone>
      <email>hanbing_li@sina.com.cn</email>
    </overall_contact>
    <location>
      <facility>
        <name>Peking union medical college hospital</name>
        <address>
          <city>Beijing</city>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <reference>
      <citation>Young NS. Aplastic anaemia. Lancet. 1995 Jul 22;346(8969):228-32. doi: 10.1016/s0140-6736(95)91273-8. No abstract available.</citation>
      <PMID>7616805</PMID>
    </reference>
    <reference>
      <citation>Young NS. Aplastic Anemia. N Engl J Med. 2018 Oct 25;379(17):1643-1656. doi: 10.1056/NEJMra1413485. No abstract available.</citation>
      <PMID>30354958</PMID>
    </reference>
    <reference>
      <citation>Bacigalupo A. How I treat acquired aplastic anemia. Blood. 2017 Mar 16;129(11):1428-1436. doi: 10.1182/blood-2016-08-693481. Epub 2017 Jan 17.</citation>
      <PMID>28096088</PMID>
    </reference>
    <reference>
      <citation>Yang C, Zhang X. Incidence survey of aplastic anemia in China. Chin Med Sci J. 1991 Dec;6(4):203-7.</citation>
      <PMID>1813058</PMID>
    </reference>
    <reference>
      <citation>Tichelli A, de Latour RP, Passweg J, Knol-Bout C, Socie G, Marsh J, Schrezenmeier H, Hochsmann B, Bacigalupo A, Samarasinghe S, Rovo A, Kulasekararaj A, Roth A, Eikema DJ, Bosman P, Bader P, Risitano A, Dufour C; SAA Working Party of the EBMT. Long-term outcome of a randomized controlled study in patients with newly diagnosed severe aplastic anemia treated with antithymocyte globulin and cyclosporine, with or without granulocyte colony-stimulating factor: a Severe Aplastic Anemia Working Party Trial from the European Group of Blood and Marrow Transplantation. Haematologica. 2020 May;105(5):1223-1231. doi: 10.3324/haematol.2019.222562. Epub 2019 Oct 3.</citation>
      <PMID>31582549</PMID>
    </reference>
    <reference>
      <citation>Kuter DJ. The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol. 2013 Jul;98(1):10-23. doi: 10.1007/s12185-013-1382-0. Epub 2013 Jul 3.</citation>
      <PMID>23821332</PMID>
    </reference>
    <reference>
      <citation>Jing FM, Zhang XL, Meng FL, Liu XM, Shi Y, Qin P, Wang L, Zhou H, Hou Y, Song Q, Peng J, Hou M. Anti-c-Mpl antibodies in immune thrombocytopenia suppress thrombopoiesis and decrease response to rhTPO. Thromb Res. 2018 Oct;170:200-206. doi: 10.1016/j.thromres.2018.08.021. Epub 2018 Aug 30.</citation>
      <PMID>30199786</PMID>
    </reference>
    <reference>
      <citation>Ghanima W, Cooper N, Rodeghiero F, Godeau B, Bussel JB. Thrombopoietin receptor agonists: ten years later. Haematologica. 2019 Jun;104(6):1112-1123. doi: 10.3324/haematol.2018.212845. Epub 2019 May 9.</citation>
      <PMID>31073079</PMID>
    </reference>
    <reference>
      <citation>Jang JH, Tomiyama Y, Miyazaki K, Nagafuji K, Usuki K, Uoshima N, Fujisaki T, Kosugi H, Matsumura I, Sasaki K, Kizaki M, Sawa M, Hidaka M, Kobayashi N, Ichikawa S, Yonemura Y, Enokitani K, Matsuda A, Ozawa K, Mitani K, Lee JW, Nakao S. Efficacy and safety of romiplostim in refractory aplastic anaemia: a Phase II/III, multicentre, open-label study. Br J Haematol. 2021 Jan;192(1):190-199. doi: 10.1111/bjh.17190. Epub 2020 Nov 5. Erratum In: Br J Haematol. 2021 May;193(3):682.</citation>
      <PMID>33152120</PMID>
    </reference>
    <reference>
      <citation>Ruan J, Zuo W, Chen M, Yang C, Han B. Eltrombopag is effective in patients with relapse/refractory aplastic anemia-report from a single center in China. Ann Hematol. 2020 Dec;99(12):2755-2761. doi: 10.1007/s00277-020-04266-1. Epub 2020 Sep 17. Erratum In: Ann Hematol. 2020 Nov 2;:</citation>
      <PMID>32944791</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 18, 2023</study_first_submitted>
    <study_first_submitted_qc>August 18, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 24, 2023</study_first_posted>
    <last_update_submitted>August 18, 2023</last_update_submitted>
    <last_update_submitted_qc>August 18, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Peking Union Medical College Hospital</investigator_affiliation>
      <investigator_full_name>Bing Han</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Anemia</mesh_term>
      <mesh_term>Anemia, Aplastic</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cyclosporine</mesh_term>
      <mesh_term>Cyclosporins</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06009497
  org study id: Romiplostim-1
  nct id: NCT06009497
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Aplastic anemia (AA) is a group of clinical syndromes caused by a significant decrease in
        bone marrow hematopoietic tissue from different etiologies, resulting in hematopoietic
        failure. Treatment options for patients with aplastic anemia are very limited. In a phase
        II/III, multicenter, open-label study exploring the efficacy and safety of romiplostim, the
        primary endpoint showed an overall response rate of 84% [95% CI 66-95%] at week 27. However,
        there are no prospective clinical data exploring whether romiplostim combined with
        ciclosporin (CsA) can further improve efficacy than ciclosporin monotherapy in newly
        diagnosed NSAA. Therefore, we aimed to compare the efficacy and safety of romiplostim in
        combination with CsA versus CsA monotherapy.
  Aplastic anemia (AA) is a group of clinical syndromes caused by a significant decrease in
        bone marrow hematopoietic tissue from different etiologies, resulting in hematopoietic
        failure. Treatment options for patients with aplastic anemia are very limited. By binding to
        the thrombopoietin (TPO) receptor, thrombopoietin receptor agonists (TPO-RAs) can cause
        conformational changes in the TPO receptor, activate the JAK2/STATS pathway, and increase
        megakaryocyte progenitor cells proliferation and platelet production. At present, TPO-RAs
        including eltrombopag, lusutrombopag, romiplostim, and avatrombopag have been approved by
        FDA. In a phase II/III, multicenter, open-label study exploring the efficacy and safety of
        romiplostim, 31 patients with refractory AA were enrolled. The primary endpoint for the
        proportion of patients who achieved any hematological (platelet, neutrophil, and red blood
        cell) response at week 27 was 84% [95% CI 66-95%]. At week 53, the three-line response rate
        was 39% (95% CI 22-58%). However, there are no prospective clinical data exploring whether
        romiplostim combined with ciclosporin (CsA) can further improve efficacy than ciclosporin
        monotherapy in newly diagnosed NSAA. Since romiplostim and CsA have good safety, if it is
        proved that the combination of the two drugs is superior to ciclosporin monotherapy, it can
        quickly improve blood patterns in NSAA, avoid the use of more expensive ATG, and provide some
        help to reduce the economic burden of AA patients.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: overall response rate (ORR)
  time frame: 3, 6 months
  description: Proportion of patients who achieved complete response and partial response.
  measure: complete response rate (CRR)
  time frame: 3, 6 months
  description: Proportion of patients who achieved complete response.
  measure: adverse event rate
  time frame: 3, 6 months
  description: All adverse events that occur or worsen during treatment, as well as those that occur later but are believed by the investigator to be related to the investigational drug, will be reported.
  arm group label: Romiplostim+CsA
  arm group type: Experimental
  description: Romiplostim 10 µg/kg, subcutaneous injection, once a week, for at least 3 months. Patients with platelet count ≥50×109/L can stop using, and continue to use with platelet count < 50×109/L.
  Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml. Ciclosporin should be used for at least 6 months to evaluate the efficacy. Effective patients will continue to use ciclosporin for at least 1.5 years, followed by a slow reduction.
  arm group label: CsA
  arm group type: Experimental
  description: Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml. Ciclosporin should be used for at least 6 months to evaluate the efficacy. Effective patients will continue to use ciclosporin for at least 1.5 years, followed by a slow reduction.
  intervention type: Drug
  intervention name: Romiplostim
  description: Romiplostim 10 µg/kg, subcutaneous injection, once a week.
  arm group label: Romiplostim+CsA
  intervention type: Drug
  intervention name: Ciclosporin
  description: Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml.
  arm group label: CsA
  arm group label: Romiplostim+CsA
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Bing Han
  phone: 13601059938
  email: hanbing_li@sina.com.cn
  facility: 
  country: China
  citation: Young NS. Aplastic anaemia. Lancet. 1995 Jul 22;346(8969):228-32. doi: 10.1016/s0140-6736(95)91273-8. No abstract available.
  PMID: 7616805
  citation: Young NS. Aplastic Anemia. N Engl J Med. 2018 Oct 25;379(17):1643-1656. doi: 10.1056/NEJMra1413485. No abstract available.
  PMID: 30354958
  citation: Bacigalupo A. How I treat acquired aplastic anemia. Blood. 2017 Mar 16;129(11):1428-1436. doi: 10.1182/blood-2016-08-693481. Epub 2017 Jan 17.
  PMID: 28096088
  citation: Yang C, Zhang X. Incidence survey of aplastic anemia in China. Chin Med Sci J. 1991 Dec;6(4):203-7.
  PMID: 1813058
  citation: Tichelli A, de Latour RP, Passweg J, Knol-Bout C, Socie G, Marsh J, Schrezenmeier H, Hochsmann B, Bacigalupo A, Samarasinghe S, Rovo A, Kulasekararaj A, Roth A, Eikema DJ, Bosman P, Bader P, Risitano A, Dufour C; SAA Working Party of the EBMT. Long-term outcome of a randomized controlled study in patients with newly diagnosed severe aplastic anemia treated with antithymocyte globulin and cyclosporine, with or without granulocyte colony-stimulating factor: a Severe Aplastic Anemia Working Party Trial from the European Group of Blood and Marrow Transplantation. Haematologica. 2020 May;105(5):1223-1231. doi: 10.3324/haematol.2019.222562. Epub 2019 Oct 3.
  PMID: 31582549
  citation: Kuter DJ. The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol. 2013 Jul;98(1):10-23. doi: 10.1007/s12185-013-1382-0. Epub 2013 Jul 3.
  PMID: 23821332
  citation: Jing FM, Zhang XL, Meng FL, Liu XM, Shi Y, Qin P, Wang L, Zhou H, Hou Y, Song Q, Peng J, Hou M. Anti-c-Mpl antibodies in immune thrombocytopenia suppress thrombopoiesis and decrease response to rhTPO. Thromb Res. 2018 Oct;170:200-206. doi: 10.1016/j.thromres.2018.08.021. Epub 2018 Aug 30.
  PMID: 30199786
  citation: Ghanima W, Cooper N, Rodeghiero F, Godeau B, Bussel JB. Thrombopoietin receptor agonists: ten years later. Haematologica. 2019 Jun;104(6):1112-1123. doi: 10.3324/haematol.2018.212845. Epub 2019 May 9.
  PMID: 31073079
  citation: Jang JH, Tomiyama Y, Miyazaki K, Nagafuji K, Usuki K, Uoshima N, Fujisaki T, Kosugi H, Matsumura I, Sasaki K, Kizaki M, Sawa M, Hidaka M, Kobayashi N, Ichikawa S, Yonemura Y, Enokitani K, Matsuda A, Ozawa K, Mitani K, Lee JW, Nakao S. Efficacy and safety of romiplostim in refractory aplastic anaemia: a Phase II/III, multicentre, open-label study. Br J Haematol. 2021 Jan;192(1):190-199. doi: 10.1111/bjh.17190. Epub 2020 Nov 5. Erratum In: Br J Haematol. 2021 May;193(3):682.
  PMID: 33152120
  citation: Ruan J, Zuo W, Chen M, Yang C, Han B. Eltrombopag is effective in patients with relapse/refractory aplastic anemia-report from a single center in China. Ann Hematol. 2020 Dec;99(12):2755-2761. doi: 10.1007/s00277-020-04266-1. Epub 2020 Sep 17. Erratum In: Ann Hematol. 2020 Nov 2;:
  PMID: 32944791
  responsible party type: Principal Investigator
  investigator affiliation: Peking Union Medical College Hospital
  investigator full name: Bing Han
  investigator title: Professor
  mesh term: Anemia
  mesh term: Anemia, Aplastic
  mesh term: Cyclosporine
  mesh term: Cyclosporins
  sharing ipd: No