Aplastic anemia (AA) MedDRA version: 20.0 Level: PT Classification code 10002967 Term: Aplastic anaemia System Organ Class: 10005329 - Blood and lymphatic system disorders MedDRA version: 20.1 Level: LLT Classification code 10002968 Term: Aplastic anaemia, unspecified System Organ Class: 10005329 - Blood and lymphatic system disorders MedDRA version: 23.0 Level: LLT Classification code 10083893 Term: Acquired aplastic anaemia System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
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Sponsors
Amgen, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject has provided informed consent prior to initiation of any study specific activities/procedures or subject’s legally authorized representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the investigator may compromise the ability of the subject to give written informed consent. 2. Age more than or equal to 18 years at time of enrollment 3. Diagnosis of severe AA or very severe AA confirmed by blood, bone marrow, and cytogenetic studies 4. An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 at screening 5. Arm 1 only: considered to require new treatment with antithymocyte globulin and CsA 6. Arm 2 only: refractory to at least 1 course of IST including horse or rabbit antithymocyte globulin; or ineligible for antithymocyte globulin treatment and refractory to CsA 7. Arm 2 only: thrombocytopenia defined as a platelet count of less than equal to 30 x 10?/L Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: Disease-Related: 1. Diagnosed as having congenital AA (Fanconi anemia, congenital dyskeratosis, etc,) Other Medical Conditions: 2. History of other malignancy within the past 5 years, with the exceptions detailed in protocol 3. Aplastic anemia with hemolytic paroxysmal nocturnal hemoglobinuria (hemolytic predominant is defined as lactate dehydrogenase [LDH] > 1.5 x the upper limit of site normal) 4. Diagnosed as having acute myeloblastic leukemia (AML) or chronic myelomonocytic leukemia 5. Concurrent thrombocytopenia of other etiologies (eg, MDS, ITP, cirrhosis) 6. Current or past history of arterial or venous thrombus within 1 year prior to consent 7. Concurrent active infection not adequately responding to appropriate therapy 8. Current or past history of hypersensitivity to recombinant Escherichia coli-derived proteins 9. Having grade 2 or higher bone marrow reticulin 10. Positive for anti-human immunodeficiency virus (HIV) antibody at screening 11. Receiving prophylactic or therapeutic treatment for hepatitis type B at screening examination (excluding prophylactic treatment for initiation of antithymocyte globulin treatment), or meeting any of the following items and having active hepatitis type B infection at screening: • Positive for hepatitis B surface antigen (HBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B). • Negative HBsAg and positive for hepatitis B core antibody: hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B. If any of the hepatitis B virus tests has an indeterminate result, confirmatory testing will be performed by an alternative method that is locally accepted. 12. Positive hepatitis C virus antibody (HCVAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C. Prior/Concomitant Therapy: 13. Arm 1 only: Previously treated with antithymocyte globulin, CsA, or Alemtuzumab 14. Previously treated with PEGylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), recombinant human TPO, romiplostim and other TPO-receptor agonist (eltrombopag, etc,) 15. Planned HSCT during the study 16. Systemic treatment with any of the following medication for the treatment of AA within 4 weeks before day 1, however, excluding their use as premedication: • anabolic steroids • corticosteroids Prior/Concurrent Clinical Study Experience: 17. Currently receiving treatment in another investigational device or drug study, or less than 16 weeks (or 5-fold of the half-life [whichever is longer]) since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded. Diagnostic Assessments: 18. Having blast cells > 2% in bone marrow at screening; 19. Any of the following laboratory abnormalities at screening: • Total bilirubin (TBL): = 1.5 times the upper limit of site normal • ALT: = 3.0 times the upper limit of site normal • Aspartate aminotransferase (AST): = 3.0 times the upper limit of site normal • Creatinine: > 2.0 mg/dL • Other abnormal laboratory values that are considered by the investigator to affect the completion of the study or evaluations 20. History of chromosome aberrations discovered in bone marrow cells within 12 weeks prior to day 1. If the sponsor’s medical expert judged not to be problematic participation in this
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Arm 1: evaluate the efficacy of romiplostim and immunosuppressive therapy (IST) in adult non Asian severe aplastic anemia (SAA) subjects who are previously untreated with IST (1L) •Arm 2: evaluate the efficacy of romiplostim treatment in adult non Asian SAA subjects who are refractory to IST (2L+) ;Secondary Objective: •Arm 1: Describe efficacy for adult non-Asian SAA subjects who are previously untreated with IST (1L) to achieve a complete response (CR) or partial response (PR) following treatment with romiplostim and IST •Describe efficacy for non-Asian adult SAA subjects treated on the 2 study arms (1L/2L+) for decreasing the frequency of platelet and/or red blood cell (RBC) transfusions, or becoming platelet and/or RBC transfusion independent •Assess overall safety of romiplostim treatment for non-Asian subjects treated on the 2 study arms (1L/2L+) •Evaluate the bleeding status from baseline to week 14 in adult non-Asian SAA subjects in the 2 study arms (1L/2L+) •Evaluate the pharmacokinetics (PK) of romiplostim when it is administered subcutaneously (SC) in adult non-Asian SAA subjects in the 2 study arms (1L/2L+) •Evaluate the immunogenicity of romiplostim when it is administered SC in adult non-Asian SAA subjects in the 2 study arms (1L/2L+) ;Primary end point(s): week 14;Timepoint(s) of evaluation of this end point: week 14 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): week 14;Timepoint(s) of evaluation of this end point: week 14 | — |
Countries
Brazil, France, United Kingdom, United States
Contacts
Public ContactMedical Information
Amgen SAS
Outcome results
None listed