Anemia, Chronic Kidney Disease
Conditions
Keywords
Anemia associated with chronic kidney disease (CKD), Hemodialysis
Brief summary
This study will evaluate the efficacy and safety of intravenous MK2578, given as maintenance treatment for renal anemia in chronic kidney disease patients on dialysis who were previously receiving erythropoietin stimulating agents.
Detailed description
This study consists of a 12-week base study (MK2578-003-AM03) and an optional 40-week extension study (MK2578-003-EXT12). Participants who complete 12 weeks of treatment in the base study will enter the extension on the most recent dose administered in the base study or a newly adjusted dose, if adjustment is required to bring Hg levels within range. Participants' doses of MK2578 will be adjusted upward or downward during the extension study to maintain Hb in the range of 10-12 g/dL.
Interventions
DRUGMK2578 1 mcg for every 350 U of Epogen (epoetin alfa) received per week at Baseline
MK2578 was to be administered IV. Participants in Cohort 2 were to receive 1 mcg of MK2578 for every 350 U of Epogen (epoetin alfa) received per week at Baseline. Participants were to be randomized to QW or QM dosing schedules within each cohort.
DRUGMK2578 1mcg for every 600 Units (U) of Epogen® (epoetin alfa) received per week at Baseline
MK2578 was to be administered intravenously (IV). Participants in Cohort 1 were to receive 1 mcg of MK2578 for every 600 U of Epogen (epoetin alfa) received per week at Baseline. Participants were to be randomized to every week (QW) or once every 4 weeks (QM) dosing schedules within each cohort.
DRUGMK2578 1 mcg for every 200 U of Epogen (epoetin alfa) received per week at Baseline
MK2578 was to be administered IV. Participants in Cohort 3 were to receive 1 mcg of MK2578 for every 200 U of Epogen (epoetin alfa) received per week at Baseline. Participants were to be randomized to QW or QM dosing schedules within each cohort.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Base Study: * Patient is male or is a female who either cannot have children or who agrees to use appropriate contraceptive measures * Patient has been on hemodialysis for at least 6 months when informed consent is signed * Patient has received intravenous epoetin alfa or epoetin beta for a least 6 months when the informed consent is signed Extension Study: * Patient completed the base study through Week 12 * Patient tolerated MK2578 and demonstrated compliance with study procedures
Exclusion criteria
* Patient has a life expectancy of less than 6 months * Patient is scheduled for a kidney transplant within the next 6 months * Patient has had a blood transfusion within 12 weeks of screening * Patient has had major surgery within 12 weeks of screening or plans to have surgery * Patient has Human Immunodeficiency Virus (HIV) * Patient has history of blood dyscrasia, hematologic disorders or any other disease known to cause anemia * Patient has severe congestive heart failure (CHF) * Patient has a history of malignant cancer, except certain skin or cervical cancers * Patient has a history of grand mal seizures within the last 6 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Composite Events of Transfusion-Related Adverse Experiences | 12 weeks |
| Change From Baseline in Hemoglobin (Hg) Level at Week 4 | 4 weeks |
| Number of Participants With Composite Events of Death, Myocardial Infarction (MI), and Cerebrovascular Accident (CVA) | 12 weeks |
| Number of Participants With Confirmed, Treatment Emergent Antibodies to MK2578 | 12 weeks |
| Number of Participants With Composite Events of Infusion Reactions | 12 weeks |
| Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | 12 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Hg Level at Week 12 | 12 weeks |
Participant flow
Recruitment details
Participants were recruited from 46 centers (9 centers in Bulgaria, 27 in United States, 3 in Romania, 4 in Italy, and 3 in Poland).
Pre-assignment details
At randomization, participants received either MK2578 or matching placebo on Day 1 and crossed over to the alternate treatment at the next dialysis treatment on Day 3.
Participants by arm
| Arm | Count |
|---|---|
| MK2578 1mcg/600U QW MK2578 IV administered QW. | 16 |
| MK2578 1mcg/600U QM MK2578 IV administered QM. | 15 |
| MK2578 1mcg/350U QW MK2578 IV administered QW. | 4 |
| MK2578 1mcg/350U QM MK2578 IV administered QM. | 4 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study terminated by sponsor | 12 | 10 |
Baseline characteristics
| Characteristic | MK2578 1mcg/350U QM | Total | MK2578 1mcg/600U QW | MK2578 1mcg/600U QM | MK2578 1mcg/350U QW |
|---|---|---|---|---|---|
| Age, Continuous | 60.5 years STANDARD_DEVIATION 4.51 | 51.0 years STANDARD_DEVIATION 12.3 | 46.3 years STANDARD_DEVIATION 14.29 | 51.7 years STANDARD_DEVIATION 10.22 | 58.0 years STANDARD_DEVIATION 8.91 |
| Sex: Female, Male Female | 3 Participants | 24 Participants | 10 Participants | 8 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 15 Participants | 6 Participants | 7 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 20 | 7 / 19 |
| serious Total, serious adverse events | 1 / 20 | 2 / 19 |
Outcome results
Primary
Change From Baseline in Hemoglobin (Hg) Level at Week 4
Time frame: 4 weeks
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK2578 1mcg/600U QW | Change From Baseline in Hemoglobin (Hg) Level at Week 4 | -0.6 g/dL | Standard Deviation 0.8 |
| MK2578 1mcg/600U QM | Change From Baseline in Hemoglobin (Hg) Level at Week 4 | -0.7 g/dL | Standard Deviation 1 |
| MK2578 1mcg/350U QW | Change From Baseline in Hemoglobin (Hg) Level at Week 4 | -1.0 g/dL | — |
| MK2578 1mcg/350U QM | Change From Baseline in Hemoglobin (Hg) Level at Week 4 | -1.0 g/dL | — |
Primary
Number of Participants With Composite Events of Death, Myocardial Infarction (MI), and Cerebrovascular Accident (CVA)
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK2578 1mcg/600U QW | Number of Participants With Composite Events of Death, Myocardial Infarction (MI), and Cerebrovascular Accident (CVA) | 0 Participants |
| MK2578 1mcg/600U QM | Number of Participants With Composite Events of Death, Myocardial Infarction (MI), and Cerebrovascular Accident (CVA) | 1 Participants |
| MK2578 1mcg/350U QW | Number of Participants With Composite Events of Death, Myocardial Infarction (MI), and Cerebrovascular Accident (CVA) | 0 Participants |
| MK2578 1mcg/350U QM | Number of Participants With Composite Events of Death, Myocardial Infarction (MI), and Cerebrovascular Accident (CVA) | 0 Participants |
Primary
Number of Participants With Composite Events of Infusion Reactions
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK2578 1mcg/600U QW | Number of Participants With Composite Events of Infusion Reactions | 0 Participants |
| MK2578 1mcg/600U QM | Number of Participants With Composite Events of Infusion Reactions | 0 Participants |
| MK2578 1mcg/350U QW | Number of Participants With Composite Events of Infusion Reactions | 0 Participants |
| MK2578 1mcg/350U QM | Number of Participants With Composite Events of Infusion Reactions | 0 Participants |
Primary
Number of Participants With Composite Events of Transfusion-Related Adverse Experiences
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK2578 1mcg/600U QW | Number of Participants With Composite Events of Transfusion-Related Adverse Experiences | 0 Participants |
| MK2578 1mcg/600U QM | Number of Participants With Composite Events of Transfusion-Related Adverse Experiences | 0 Participants |
| MK2578 1mcg/350U QW | Number of Participants With Composite Events of Transfusion-Related Adverse Experiences | 0 Participants |
| MK2578 1mcg/350U QM | Number of Participants With Composite Events of Transfusion-Related Adverse Experiences | 0 Participants |
Primary
Number of Participants With Confirmed, Treatment Emergent Antibodies to MK2578
Time frame: 12 weeks
Population: Immunogenicity assays for antibodies to MK2578 were not performed due to early study termination.
Primary
Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia
Time frame: 12 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MK2578 1mcg/600U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Pure red cell aplasia | 0 Participants |
| MK2578 1mcg/600U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | CHF | 0 Participants |
| MK2578 1mcg/600U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Vascular access thrombosis | 0 Participants |
| MK2578 1mcg/600U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Peripheral vascular thromboses | 0 Participants |
| MK2578 1mcg/600U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | MI | 0 Participants |
| MK2578 1mcg/600U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Death | 0 Participants |
| MK2578 1mcg/600U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Seizure | 0 Participants |
| MK2578 1mcg/600U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Hypertension | 1 Participants |
| MK2578 1mcg/600U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | CVA | 0 Participants |
| MK2578 1mcg/600U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Hypertension | 1 Participants |
| MK2578 1mcg/600U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Death | 0 Participants |
| MK2578 1mcg/600U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | MI | 1 Participants |
| MK2578 1mcg/600U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | CVA | 0 Participants |
| MK2578 1mcg/600U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Peripheral vascular thromboses | 0 Participants |
| MK2578 1mcg/600U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Vascular access thrombosis | 0 Participants |
| MK2578 1mcg/600U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | CHF | 0 Participants |
| MK2578 1mcg/600U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Seizure | 0 Participants |
| MK2578 1mcg/600U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Pure red cell aplasia | 0 Participants |
| MK2578 1mcg/350U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Death | 0 Participants |
| MK2578 1mcg/350U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | CVA | 0 Participants |
| MK2578 1mcg/350U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Pure red cell aplasia | 0 Participants |
| MK2578 1mcg/350U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | CHF | 0 Participants |
| MK2578 1mcg/350U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Hypertension | 0 Participants |
| MK2578 1mcg/350U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | MI | 0 Participants |
| MK2578 1mcg/350U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Seizure | 0 Participants |
| MK2578 1mcg/350U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Peripheral vascular thromboses | 0 Participants |
| MK2578 1mcg/350U QW | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Vascular access thrombosis | 1 Participants |
| MK2578 1mcg/350U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | CVA | 0 Participants |
| MK2578 1mcg/350U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Vascular access thrombosis | 0 Participants |
| MK2578 1mcg/350U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Pure red cell aplasia | 0 Participants |
| MK2578 1mcg/350U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Peripheral vascular thromboses | 0 Participants |
| MK2578 1mcg/350U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Seizure | 0 Participants |
| MK2578 1mcg/350U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | CHF | 0 Participants |
| MK2578 1mcg/350U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | MI | 0 Participants |
| MK2578 1mcg/350U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Death | 0 Participants |
| MK2578 1mcg/350U QM | Number of Participants With Events of Death, MI, CVA, Peripheral Vascular Thromboses, Vascular Access Thrombosis, Congestive Heart Failure (CHF), Hypertension, Seizure, or Pure Red Cell Aplasia | Hypertension | 0 Participants |
Secondary
Change From Baseline in Hg Level at Week 12
Time frame: 12 weeks
Population: Full analysis set; due to study termination participants in the MK2578 1mcg/350U QW and MK2578 1mcg/350U QM were not analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK2578 1mcg/600U QW | Change From Baseline in Hg Level at Week 12 | -0.1 g/dL | Standard Deviation 1.4 |
| MK2578 1mcg/600U QM | Change From Baseline in Hg Level at Week 12 | -0.5 g/dL | Standard Deviation 1.4 |