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Efficacy of Romiplostim in Treatment of SAA in Adults Previously Untreated With or Refractory to Immunosuppressive Therapy

Primary Purpose

Severe Aplastic Anemia (SAA)

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Romiplostim
Antithymocyte Globulin
Cyclosporine A
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Aplastic Anemia (SAA) focused on measuring Severe Aplastic Anemia, SAA, Very Severe Aplastic Anemia, vSAA, Romiplostim

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥ 18 years at time of enrollment
  • Diagnosis of severe aplastic anemia (AA) or very severe AA confirmed by blood, bone marrow, and cytogenetic studies
  • An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 at screening
  • Arm 1 only: considered to require new treatment with anti-thymocyte globulin (ATG) and cyclosporine A (CsA)
  • Arm 2 only: refractory to at least one course of immunosuppressive therapy including horse or rabbit ATG; or ineligible for ATG treatment and refractory to CsA
  • Arm 2 only: thrombocytopenia defined as a platelet count of ≤ 30 x 10⁹/L

Exclusion Criteria:

  • Participants with Asian ethnicity
  • Diagnosed as having congenital AA (Fanconi anemia, congenital dyskeratosis, etc)
  • History of other malignancy within the past 5 years, with exceptions.
  • Aplastic anemia with hemolytic paroxysmal nocturnal hemoglobinuria (PNH) (hemolytic predominant is defined as lactate dehydrogenase (LDH) > 1.5 x the upper limit of site normal
  • Arm 1 only: Previously treated with ATG, CsA, or Alemtuzumab
  • Previously treated with PEGylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), recombinant human thrombopoietin protein (TPO), romiplostim and other TPO-receptor agonist (eltrombopag, etc)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Arm 1: Previously Untreated IST

    Arm 2: Refractory IST

    Arm Description

    Participants with SAA/vSAA that are previously untreated with IST.

    Participants with SAA/vSAA that are refractory to IST.

    Outcomes

    Primary Outcome Measures

    Arms 1 and 2: proportion of participants achieving any hematologic response at week 14
    Proportion of participants achieving any hematologic response at week 14 based on response criteria: Platelet response Erythroid response Red blood cell count Hemoglobin concentration Neutrophil response

    Secondary Outcome Measures

    Arm 1: number of participants who achieve a complete response (CR) or partial response (PR) at week 14
    Arms 1 and 2: number of participants who have a decrease in frequency of platelet and/or red blood cell (RBC) transfusions, or become platelet and/or RBC transfusion independent at week 14
    Arms 1 and 2: number of participants with serious adverse events
    Arms 1 and 2: number of participants with clinically significant changes in laboratory values
    Arms 1 and 2: change from baseline in Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) bleeding scale at week 14
    The Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto is as follows: 0: No bleeding Petecjoae or mucosal or retinal bleeding that did not require red-cell transfusion Melena, hematemesis, hematuria, or hemoptysis Any bleeding that required red-cell transfusion Retinal bleeding accompanied by visual impairment Nonfatal cerebral bleeding Fatal cerebral bleeding Fatal noncerebral bleeding
    Arms 1 and 2: serum romiplostim trough concentrations
    Arms 1 and 2: maximum serum concentration (Cmax) of romiplostim
    Arms 1 and 2: area under the curve (AUC) of romiplostim
    Arms 1 and 2: time to reach maximum concentration (tmax) of romiplostim
    Arms 1 and 2: half-life (t1/2) of romiplostim
    Arms 1 and 2: number of participant with anti-romiplostim antibodies
    Arms 1 and 2: number of participants with antibodies to thrombopoietin

    Full Information

    First Posted
    April 5, 2022
    Last Updated
    September 28, 2023
    Sponsor
    Amgen
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05323617
    Brief Title
    Efficacy of Romiplostim in Treatment of SAA in Adults Previously Untreated With or Refractory to Immunosuppressive Therapy
    Official Title
    Two Arm Bridging Study to Evaluate the Efficacy of Romiplostim in the Treatment of Adult Severe Aplastic Anemia Participants Who Are Either Previously Untreated With IST or Refractory to IST
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Operational
    Study Start Date
    August 31, 2023 (Anticipated)
    Primary Completion Date
    February 25, 2025 (Anticipated)
    Study Completion Date
    February 25, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Amgen

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Romiplostim has been used in clinical trials for the treatment of severe and very severe aplastic anemia (SAA/vSAA) in Asian participants who are either previously untreated with immunosuppressive therapy (IST) or refractory to IST. This study will evaluate the efficacy of romiplostim in the treatment of participants with SAA/vSAA. The primary objectives of this study are to: Arm 1: Evaluate the efficacy of romiplostim and IST in adult SAA/vSAA participants who are previously untreated with IST (1L) Arm 2: Evaluate the efficacy of romiplostim treatment in adult SAA/vSAA participants who are refractory to IST (2L+)

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Severe Aplastic Anemia (SAA)
    Keywords
    Severe Aplastic Anemia, SAA, Very Severe Aplastic Anemia, vSAA, Romiplostim

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Arm 1: Previously Untreated IST
    Arm Type
    Experimental
    Arm Description
    Participants with SAA/vSAA that are previously untreated with IST.
    Arm Title
    Arm 2: Refractory IST
    Arm Type
    Experimental
    Arm Description
    Participants with SAA/vSAA that are refractory to IST.
    Intervention Type
    Drug
    Intervention Name(s)
    Romiplostim
    Other Intervention Name(s)
    Nplate®
    Intervention Description
    Administered as a subcutaneous injection.
    Intervention Type
    Drug
    Intervention Name(s)
    Antithymocyte Globulin
    Intervention Description
    Horse or rabbit antithymocyte globulin administered as an intravenous infusion.
    Intervention Type
    Drug
    Intervention Name(s)
    Cyclosporine A
    Intervention Description
    Administered orally.
    Primary Outcome Measure Information:
    Title
    Arms 1 and 2: proportion of participants achieving any hematologic response at week 14
    Description
    Proportion of participants achieving any hematologic response at week 14 based on response criteria: Platelet response Erythroid response Red blood cell count Hemoglobin concentration Neutrophil response
    Time Frame
    Week 14
    Secondary Outcome Measure Information:
    Title
    Arm 1: number of participants who achieve a complete response (CR) or partial response (PR) at week 14
    Time Frame
    Week 14
    Title
    Arms 1 and 2: number of participants who have a decrease in frequency of platelet and/or red blood cell (RBC) transfusions, or become platelet and/or RBC transfusion independent at week 14
    Time Frame
    Week 14
    Title
    Arms 1 and 2: number of participants with serious adverse events
    Time Frame
    24 Weeks
    Title
    Arms 1 and 2: number of participants with clinically significant changes in laboratory values
    Time Frame
    24 Weeks
    Title
    Arms 1 and 2: change from baseline in Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) bleeding scale at week 14
    Description
    The Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto is as follows: 0: No bleeding Petecjoae or mucosal or retinal bleeding that did not require red-cell transfusion Melena, hematemesis, hematuria, or hemoptysis Any bleeding that required red-cell transfusion Retinal bleeding accompanied by visual impairment Nonfatal cerebral bleeding Fatal cerebral bleeding Fatal noncerebral bleeding
    Time Frame
    Baseline and Week 14
    Title
    Arms 1 and 2: serum romiplostim trough concentrations
    Time Frame
    Prior to romiplostim administration on Weeks 1, 2, 4, 5, 9, 13, and 24
    Title
    Arms 1 and 2: maximum serum concentration (Cmax) of romiplostim
    Time Frame
    Weeks 1, 2, 4, 5, 9, 13, and 24
    Title
    Arms 1 and 2: area under the curve (AUC) of romiplostim
    Time Frame
    Weeks 1, 2, 4, 5, 9, 13, and 24
    Title
    Arms 1 and 2: time to reach maximum concentration (tmax) of romiplostim
    Time Frame
    Weeks 1, 2, 4, 5, 9, 13, and 24
    Title
    Arms 1 and 2: half-life (t1/2) of romiplostim
    Time Frame
    Weeks 1, 2, 4, 5, 9, 13, and 24
    Title
    Arms 1 and 2: number of participant with anti-romiplostim antibodies
    Time Frame
    Prior to romiplostim administration on Weeks 1 and 13
    Title
    Arms 1 and 2: number of participants with antibodies to thrombopoietin
    Time Frame
    Prior to romiplostim administration on Weeks 1 and 13

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age ≥ 18 years at time of enrollment Diagnosis of SAA/vSAA confirmed by blood, bone marrow, and cytogenetic studies An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 at screening Arm 1 only: participant requires initial treatment for SAA/vSAA, no matched related donor is available for allogenic hematopoietic cell transplantation (HCT) and will begin IST with antithymocyte globulin and CsA Arm 2 only: refractory to at least one course of immunosuppressive therapy including horse or rabbit ATG; or ineligible for ATG treatment and refractory to CsA Exclusion Criteria: Diagnosed as having congenital aplastic anemia (AA) (Fanconi anemia, congenital dyskeratosis, etc) History of other malignancy within the past 5 years, with exceptions. Aplastic anemia with hemolytic paroxysmal nocturnal hemoglobinuria (PNH) (hemolytic predominant is defined as lactate dehydrogenase (LDH) > 1.5 x the upper limit of site normal Arm 1 only: Previously treated with ATG, CsA, or Alemtuzumab Previously treated with PEGylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), recombinant human thrombopoietin protein (TPO), romiplostim and other TPO-receptor agonist (eltrombopag, etc) Patients who are eligible for allogenic HCT and have an available matched related donor
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    MD
    Organizational Affiliation
    Amgen
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
    IPD Sharing Time Frame
    Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
    IPD Sharing Access Criteria
    Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
    IPD Sharing URL
    http://www.amgen.com/datasharing
    Links:
    URL
    http://www.amgentrials.com
    Description
    AmgenTrials clinical trials website

    Learn more about this trial

    Efficacy of Romiplostim in Treatment of SAA in Adults Previously Untreated With or Refractory to Immunosuppressive Therapy

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