Anemic Patients With IPSS Low- or Intermediate-1-Risk Myelodysplastic Syndromes MedDRA version: 13.1 Level: LLT Classification code 10002272 Term: Anemia System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Trade Name: EPREX
Product Name: EPOETIN ALFA
Product Code: EPO
Pharmaceutical Form: Solution for injection
INN or Proposed INN: EPOETIN ALFA
CAS Number: 113427-24-0
Concentration unit: IU/ml internati
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subject at least18 years of age; 2. Diagnosis of MDS according to WHO or FAB pathologic classification (confirmed via bone marrow aspirate); 3. Documentation of an IPSS score indicating Low- or Intermediate-1-risk disease; 4. Hemoglobin concentration at screening and baseline (before the first dose of study drug) of 10.0 g/dL or less; Note: assessment should be based on untransfused hemoglobin, ie, the subject did not receive an RBC transfusion within the previous week. 5. Screening serum erythropoietin concentration of less than 500 mU/mL; 6. RBC transfusion requirement of less than 4 RBC units over the last 8 weeks before randomization; 7. Screening Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2; 8. Adequate iron stores, defined as serum ferritin greater than 100 ng/mL, transferrin saturation greater than 20%, or both, measured within the 2-week screening period, or adequate iron stores as demonstrated by recent (within 12 weeks) bone marrow examination with iron stain; 9. Documentation of adequate vitamin B12 and folate levels (above the lower limit of the reference range for the laboratory performing the assay), measured at screening and baseline; 10. Female subjects with reproductive potential must be surgically sterile, abstinent, or practicing an effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, male partner sterilization) before entry and throughout the study and have a negative urine or serum beta-human chorionic gonadotropin (hCG) pregnancy test at screening (all female subjects with reproductive potential) and at Week 24 (female subjects with reproductive potential continuing in the treatment extension phase); 11. Willingness to adhere to the prohibitions and restrictions specified in this protocol; 12. Subjects (or their legally acceptable representatives) must sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. 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 48 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 111 ;Inclusion criteria: 1. Male or female subject at least18 years of age; 2. Diagnosis of MDS according to WHO or FAB pathologic classification (confirmed via bone marrow aspirate); 3. Documentation of an IPSS score indicating Low- or Intermediate-1-risk disease; 4. Hemoglobin concentration at screening and baseline (before the first dose of study drug) of 10.0 g/dL or less; Note: assessment should be based on untransfused hemoglobin, ie, the subject did not receive an RBC transfusion within the previous week. 5. Screening serum erythropoietin concentration of less than 500 mU/mL; 6. RBC transfusion requirement of less than 4 RBC units over the last 8 weeks before randomization; 7. Screening Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2; 8. Adequate iron stores, defined as serum ferritin greater than 100 ng/mL, transferrin saturation greater than 20%, or both, measured within the 2-week screening period, or adequate iron stores as demonstrated by recent (within 12 weeks) bone marrow examination with iron stain; 9. Documentation of adequate vitamin B12 and folate levels (above the lower limit of the reference range for the laboratory performing the assay), measured at screening and baseline; 10. Female subjects with reproductive potential must be surgically sterile, abstinent, or practicing an effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, male partner sterilization) before entry and throughout the study and have a negative urine or serum beta-human chorionic gonadotropin (hCG) pregnancy test at screening (all female subjects with reproductive potential) and at Week 24 (female subjects with reproductive potential continuing in the treatment extension phase); 11. Willingness to adhere to the prohibitions and restrictions specified in this protocol; 12. Subjects (or their legally acceptable representatives) must sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. 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 48 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 111 ;Inclusion criteria: 1. Male or female subject at least18 years of age; 2. Diagnosis of MDS according to WHO or FAB pathologic classification (confirmed via bone marrow aspirate); 3. Documentation of an IPSS score indicating Low- or Intermediate-1-risk disease; 4. Hemoglobin concentration at screening and baseline (before the first dose of study drug) of 10.0 g/dL or less; Note: assessment should be based on untransfused hemoglobin, ie, the subject did not receive an RBC transfusion within the previous week. 5. Screening serum erythropoietin concentration of less than 500 mU/mL; 6. RBC transfusion requirement of less than 4 RBC units over the last 8 weeks before randomization; 7. Screening Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2; 8. Adequate iron stores, defined as serum ferritin greater than 100 ng/mL, transferrin saturation greater than 20%, or both, measured within the 2-week screening period, or adequate iron stores as demonstrated by recent (within 12 weeks) bone marrow examination with iron stain; 9. Documentation of adequate vitamin B12 and folate levels (above the lower limit of the reference range for the laboratory performing the assay), measured at screening and baseline; 10. Female subjects with reproductive potential must be surgically sterile, abstinent, or practicing an effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, male partner sterilization) before entry and throughout the study and have a negative urine or serum beta-human chorionic gonadotropin (hCG) pregnancy test at screening (all female subjects with reproductive potential) and at Week 24 (female subjects with reproductive potential continuing in the treatment extension phase); 11. Willingness to adhere to the prohibitions and restrictions specified in this protocol; 12. Subjects (or their legally acceptable representatives) must sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. 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 48 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 111
Exclusion criteria
Exclusion criteria: 1. Anemia attributed to factors other than MDS (including hemolysis, chronic renal failure, hepatitis, gastrointestinal bleeding); 2. Secondary MDS (ie, MDS arising after chemotherapy, immunotherapy or radiation therapy/exposure); 3. Active malignancy within the past year, except basal cell or carcinoma in situ of the cervix or breast; 4. Prior therapy with epoetin alfa or any other approved or experimental ESA (eg, epoetin beta, darbepoetin) for more than 8 weeks before randomization; 5. Prior use of approved or experimental agents for the treatment of MDS; 6. History (within 6 months) of DVT (including proximal and distal), pulmonary embolism, or other venous thrombosis; Note: prior superficial thrombophlebitis is not an exclusion criterion. 7. Clinically significant, uncontrolled disease or dysfunction of the pulmonary, cardiovascular, endocrine, neurologic, gastrointestinal, or genitourinary systems not attributable to MDS; 8. Uncontrolled hypertension (defined as a systolic pressure of 160 mmHg or higher, or a diastolic pressure of 110 mmHg or higher, or both); 9. Less than 2 weeks since prior androgens or corticosteroids for the treatment of MDS; 10. Prior (within the previous 2 weeks) treatment with G-CSF or granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of neutropenia; Note: in case of neutropenic fever, use of these agents is not an exclusion criterion. 11. Known history of human immunodeficiency virus (HIV) seropositivity; 12. History (within 6 months) of cerebrovascular accident (including ischemic, embolic, and hemorrhagic cerebrovascular accident), transient ischemic attack, acute coronary syndrome (including myocardial ischemia, unstable angina, Q-wave myocardial infarction, non-Q-wave myocardial infarction), or other arterial thrombosis; 13. Known history of inherited conditions that predispose the subject to thrombosis (eg, AT3 deficiency, Factor V Leiden); 14. New-onset seizures (within 3 months before randomization) or poorly controlled seizures; 15. Pregnancy or breastfeeding; 16. Known hypersensitivity to mammalian cell-derived products or to human albumin; 17. Use of experimental agents or devices for any reason within 4 weeks before randomization; 18. Major infection requiring hospitalization and antibiotic use within 2 weeks before randomization; 19. Major surgery within 4 weeks before randomization or planned major surgery during the study period; 20. Planned stem cell harvest of bone marrow or high-dose chemotherapy with stem cell transplantation during the study period; 21. Previous bone marrow or stem cell transplantation; 22. History of PRCA and/or antibody against erythropoietin; 23. Employee of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center and family members of the employees or the investigator. ;Exclusion criteria: 1. Anemia attributed to factors other than MDS (including hemolysis, chronic renal failure, hepatitis, gastrointestinal bleeding); 2. Secondary MDS (ie, MDS arising after chemotherapy, immunotherapy or radiation therapy/exposure); 3. Active malignancy within the past year, except basal cell or carcinoma in situ of the cervix or breast; 4. Prior therapy with epoetin alfa or any other approved or experimental ESA (eg, epoetin beta, darbepoetin) for more than 8 weeks before randomization; 5. Prior use of approved or experimental agents for the treatment of MDS; 6. History (within 6 months) of DVT (including proximal and distal), pulmonary embolism, or other venous thrombosis; Note: prior superficial thrombophlebitis is not an exclusion criterion. 7. Clinically significant, uncontrolled disease or dysfunction of the pulmonary, cardiovascular, endocrine, neurologic, gastrointestinal, or genitourinary systems not attributable to MDS; 8. Uncontrolled hypertension (defined as a systolic pressure of 160 mmHg or higher, or a diastolic pressure of 110 mmHg or higher, or both); 9. Less than 2 weeks since prior androgens or corticosteroids for the treatment of MDS; 10. Prior (within the previous 2 weeks) treatment with G-CSF or granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of neutropenia; Note: in case of neutropenic fever, use of these agents is not an exclusion criterion. 11. Known history of human immunodeficiency virus (HIV) seropositivity; 12. History (within 6 months) of cerebrovascular accident (including ischemic, embolic, and hemorrhagic cerebrovascular accident), transient ischemic attack, acute coronary syndrome (including myocardial ischemia, unstable angina, Q-wave myocardial infarction, non-Q-wave myocardial infarction), or other arterial thrombosis; 13. Known history of inherited conditions that predispose the subject to thrombosis (eg, AT3 deficiency, Factor V Leiden); 14. New-onset seizures (within 3 months before randomization) or poorly controlled seizures; 15. Pregnancy or breastfeeding; 16. Known hypersensitivity to mammalian cell-derived products or to human albumin; 17. Use of experimental agents or devices for any reason within 4 weeks before randomization; 18. Major infection requiring hospitalization and antibiotic use within 2 weeks before randomization; 19. Major surgery within 4 weeks before randomization or planned major surgery during the study period; 20. Planned stem cell harvest of bone marrow or high-dose chemotherapy with stem cell transplantation during the study period; 21. Previous bone marrow or stem cell transplantation; 22. History of PRCA and/or antibody against erythropoietin; 23. Employee of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center and family members of the employees or the investigator. ;Exclusion criteria: 1. Anemia attributed to factors other than MDS (including hemolysis, chronic renal failure, hepatitis, gastrointestinal bleeding); 2. Secondary MDS (ie, MDS arising after chemotherapy, immunotherapy or radiation therapy/exposure); 3. Active malignancy within the past year, except basal cell or carcinoma in situ of the cervix or breast; 4. Prior therapy with epoetin alfa or any other approved or experimental ESA (eg, epoetin beta, darbepoetin) for more than 8 weeks before randomization; 5. Prior use of approved or experimental agents for the treatment of MDS; 6. History (within 6 months) of DVT (including proximal and distal), pulmonary embolism, or other venous thrombosis; Note: prior superficial thrombophlebitis is not an exclusion criterion. 7. Clinically significant, uncontrolled disease or dysfunction of the pulmonary, cardiovascular, endocrine, neurologic, gastrointestinal, or genitourinary systems not attributable to MDS; 8. Uncontrolled hypertension (defined as a systolic pressure of 160 mmHg or higher, or a diastolic pressure of 110 mmHg or higher, or both); 9. Less than 2 weeks since prior androgens or corticosteroids for the treatment of MDS; 10. Prior (within the previous 2 weeks) treatment with G-CSF or granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of neutropenia; Note: in case of neutropenic fever, use of these agents is not an exclusion criterion. 11. Known history of human immunodeficiency virus (HIV) seropositivity; 12. History (within 6 months) of cerebrovascular accident (including ischemic, embolic, and hemorrhagic cerebrovascular accident), transient ischemic attack, acute coronary syndrome (including myocardial ischemia, unstable angina, Q-wave myocardial infarction, non-Q-wave myocardial infarction), or other arterial thrombosis; 13. Known history of inherited conditions that predispose the subject to thrombosis (eg, AT3 deficiency, Factor V Leiden); 14. New-onset seizures (within 3 months before randomization) or poorly controlled seizures; 15. Pregnancy or breastfeeding; 16. Known hypersensitivity to mammalian cell-derived products or to human albumin; 17. Use of experimental agents or devices for any reason within 4 weeks before randomization; 18. Major infection requiring hospitalization and antibiotic use within 2 weeks before randomization; 19. Major surgery within 4 weeks before randomization or planned major surgery during the study period; 20. Planned stem cell harvest of bone marrow or high-dose chemotherapy with stem cell transplantation during the study period; 21. Previous bone marrow or stem cell transplantation; 22. History of PRCA and/or antibody against erythropoietin; 23. Employee of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center and family members of the employees or the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that epoetin alfa treatment is better at improving anemia outcome (as evaluated by Erythroid response – International Working Group [IWG] 2006) in subjects with International Prognostic Scoring Systems (IPSS) Low- or Intermediate-1-risk myelodysplastic syndromes (MDS), compared with placebo, through Week 24.;Secondary Objective: The secondary objectives include: - For responders at Week 24, observe the duration of the response through Week 48. - To assess the proportion of responders at Week 24 maintaining response through Week 48 (as measured by Erythroid response – IWG 2006). - To compare time to first RBC transfusion, transfusion-free intervals, and number of RBC units transfused. - To measure and compare changes in patient-reported outcome (PRO)/quality of life from baseline via the Functional Assessment of Cancer Therapy - Anemia/Fatigue (FACT-An) and EuroQol 5-dimension (EQ-5D) questionnaires. - To collect medical resource utilization data that may be used in future economic modeling (the construction and reporting of the economic model will be conducted separately from this study). Overall safety will also be assessed.;Primary end point(s): The primary efficacy endpoint is the proportion of subjects at Week 24 with improved anemia outcome, defined as Erythroid response according to the IWG 2006 criteria.;Timepoint(s) of evaluation of this end point: week 24;Main Objective: To demonstrate that epoetin alfa treatment is better at improving anemia outcome (as evaluated by Erythroid response – International Working Group [IWG] 2006) in subjects with International Prognostic Scoring Systems (IPSS) Low- or Intermediate-1-risk myelodysplastic syndromes (MDS), compared with placebo, through Week 24.;Secondary Objective: The secondary objectives include: - For responders at Week 24, observe the duration of the response through Week 48. - To assess the proportion of responders at Week 24 maintaining response through Week 48 (as measured b | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints are: - For responders at Week 24, the duration of the response through Week 48. - The proportion of responders at Week 24 maintaining response through Week 48 (as measured by Erythroid response – IWG 2006). -Time to first RBC transfusion, transfusion-free intervals, and number of RBC units transfused. - Change from baseline in PRO/quality of life (as assessed with the FACT-An and EQ-5D).;Timepoint(s) of evaluation of this end point: week 48;Secondary end point(s): The secondary efficacy endpoints are: - For responders at Week 24, the duration of the response through Week 48. - The proportion of responders at Week 24 maintaining response through Week 48 (as measured by Erythroid response – IWG 2006). -Time to first RBC transfusion, transfusion-free intervals, and number of RBC units transfused. - Change from baseline in PRO/quality of life (as assessed with the FACT-An and EQ-5D).;Timepoint(s) of evaluation of this end point: week 48;Secondary end point(s): The secondary efficacy endpoints are: - For responders at Week 24, the duration of the response through Week 48. - The proportion of responders at Week 24 maintaining response through Week 48 (as measured by Erythroid response – IWG 2006). -Time to first RBC transfusion, transfusion-free intervals, and number of RBC units transfused. - Change from baseline in PRO/quality of life (as assessed with the FACT-An and EQ-5D).;Timepoint(s) of evaluation of this end point: week 48 | — |
Countries
Bulgaria, France, Germany, Greece, Italy, Russian Federation, Spain
Contacts
Public ContactClinical Registry Group;Clinical Registry Group;Clinical Registry Group ;;
Janssen-Cilag International NV;Janssen-Cilag International NV;Janssen-Cilag International NV
Outcome results
None listed