Myelodysplastic Syndromes
Conditions
Brief summary
This is a Phase IV, prospective, multi-center, open-label study to assess the effectiveness and safety profile of epoetin beta (Recormon®) for treatment of symptomatic anemia in adult participants associated with low/intermediate-1-risk MDS. After screening, eligible participants will be treated with epoetin beta as recommended in the approved label and international guidelines for the use of epoetin in MDS participants and the dosage will be adjusted on the basis of erythroid response.
Interventions
DRUGEpoetin beta
Epoetin beta 30,000 or 60,000 IU per week SC injection
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult participants with low or intermediate-1 risk MDS * No previous treatment with hematopoietic growth factors within 3 months prior to screening * Symptomatic anemia (hemoglobin \<10 g/dL) as determined by investigator * Serum erythropoietin \<500 milliunits/milliliter (mU/mL) within 14 days prior to the first dose of study treatment * Require no red blood cell transfusion or dependent on \<4 units within 8 weeks prior to screening * Clinically stable for at least 1 month prior to entry into the study * For female participants of childbearing potential and male participants with partners of childbearing potential, agreement (by participants and/or partner) to use highly effective form(s) of contraception
Exclusion criteria
* Contraindications and/or known hypersensitivity to the active substance and/or any of the excipients of epoetin beta treatment * Poorly controlled hypertension as assessed by the investigator * History of Acute Myeloid Leukemia (AML) or high risk for AML * Administration of another investigational drug within 1 month before screening or planned during the study period * Previously documented evidence of Pure Red Cell Aplasia (PRCA)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Achieving Erythroid Response at Week 12 as Assessed by International Working Group (IWG) 2006 Response Criteria | Week 12 | Erythroid response at Week 12 according to IWG 2006 criteria was defined as a hemoglobin (Hb) increase of \>/= 1.5 grams/deciliter (g/dL), and a reduction of units of red blood cell (RBC) transfusions by at least 4 transfusions/8 weeks compared with the pre-treatment transfusion number in the previous 8 weeks. Only RBC transfusions given for an Hb of \</= 9.0 g/dL pre-treatment were counted in the RBC transfusion response evaluation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Platelet Response (in Participants With Pre-Treatment Platelets <100*10^9 Per Liter) at Week 12 as Assessed by IWG 2006 Response Criteria | Week 12 | Platelet response according to IWG 2006 criteria was defined as an absolute increase of \>/= 30x10\^9/L for participants starting with \>20x10\^9/L platelets. |
| Percentage of Participants With Neutrophil Response (in Participants With Pre-Treatment Neutrophil <1.0*10^9 Per Liter) at Week 12 as Assessed by IWG 2006 Response Criteria | Week 12 | Neutrophil response according to IWG 2006 criteria was defined as at least 100% increase and an absolute increase of \>0.5x10\^9/L. |
| Percentage of Participants With Adverse Events | From signing of informed consent up to 4 weeks after last dose (up to 18 weeks) | — |
Countries
Thailand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Epoetin Beta Participants received epoetin beta at an initial dose of 30,000 International Units (IU) per week administered subcutaneously (SC). Initial response was evaluated at Week 4 and the subsequent dose was based on response: for hemoglobin levels \>/= 12 grams per deciliter (g/dL), epoetin beta was discontinued until levels were \</= 10 g/dL; for hemoglobin levels \<12 g/dL and that increased less than 1 g/dL, 60,000 IU of epoetin beta were administered until Week 12; and for hemoglobin levels \<12 g/dL and that increased \>/= 1 g/dL, 30,000 IU of epoetin beta were administered until Week 12. | 99 |
| Total | 99 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 4 |
| Overall Study | Physician Decision | 4 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Epoetin Beta |
|---|---|
| Age, Continuous | 72.9 Years STANDARD_DEVIATION 10.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 99 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 99 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 69 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 99 |
| other Total, other adverse events | 48 / 99 |
| serious Total, serious adverse events | 21 / 99 |
Outcome results
Primary
Proportion of Participants Achieving Erythroid Response at Week 12 as Assessed by International Working Group (IWG) 2006 Response Criteria
Erythroid response at Week 12 according to IWG 2006 criteria was defined as a hemoglobin (Hb) increase of \>/= 1.5 grams/deciliter (g/dL), and a reduction of units of red blood cell (RBC) transfusions by at least 4 transfusions/8 weeks compared with the pre-treatment transfusion number in the previous 8 weeks. Only RBC transfusions given for an Hb of \</= 9.0 g/dL pre-treatment were counted in the RBC transfusion response evaluation.
Time frame: Week 12
Population: Efficacy analysis was performed on the intent-to-treat (ITT) population, defined as all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Epoetin Beta | Proportion of Participants Achieving Erythroid Response at Week 12 as Assessed by International Working Group (IWG) 2006 Response Criteria | 60 Participants |
Secondary
Percentage of Participants With Adverse Events
Time frame: From signing of informed consent up to 4 weeks after last dose (up to 18 weeks)
Population: The safety population included all participants that received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoetin Beta | Percentage of Participants With Adverse Events | 48.48 Percentage of Participants |
Secondary
Percentage of Participants With Neutrophil Response (in Participants With Pre-Treatment Neutrophil <1.0*10^9 Per Liter) at Week 12 as Assessed by IWG 2006 Response Criteria
Neutrophil response according to IWG 2006 criteria was defined as at least 100% increase and an absolute increase of \>0.5x10\^9/L.
Time frame: Week 12
Population: Efficacy analysis was performed on the intent-to-treat (ITT) population, defined as all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoetin Beta | Percentage of Participants With Neutrophil Response (in Participants With Pre-Treatment Neutrophil <1.0*10^9 Per Liter) at Week 12 as Assessed by IWG 2006 Response Criteria | 33.3 Percentage of Participants |
Secondary
Percentage of Participants With Platelet Response (in Participants With Pre-Treatment Platelets <100*10^9 Per Liter) at Week 12 as Assessed by IWG 2006 Response Criteria
Platelet response according to IWG 2006 criteria was defined as an absolute increase of \>/= 30x10\^9/L for participants starting with \>20x10\^9/L platelets.
Time frame: Week 12
Population: Efficacy analysis was performed on the intent-to-treat (ITT) population, defined as all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoetin Beta | Percentage of Participants With Platelet Response (in Participants With Pre-Treatment Platelets <100*10^9 Per Liter) at Week 12 as Assessed by IWG 2006 Response Criteria | 16 Percentage of Participants |