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Withdrawn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
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
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
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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