Anemia, Chronic Kidney Disease
Conditions
Keywords
Anemia
Brief summary
This study will define an effective starting dose for subcutaneous administration of MK2578 to correct anemia in erythropoiesis-stimulating agent (ESA)-naive patients with chronic kidney disease (CKD) who are not on dialysis while evaluating its safety.
Interventions
DRUGMK2578
MK2578 1.0 mcg/kg/month
DRUGComparator: darbepoetin alfa
darbepoetin alfa
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Patient is male or is a female who either cannot have children or who agrees to use appropriate contraceptive measures * Patient has chronic kidney disease
Exclusion criteria
* Patient is morbidly obese * Patient has used another erythropoiesis (red blood cell formation) stimulating agent within 12 weeks of screening * Patient will require dialysis during the study or is planning to have 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 the past 12 weeks or plans to have surgery * Patient has Human Immunodeficiency Virus (HIV) * Patient has a history of diseases other than CKD known to cause anemia * Patient has severe congestive heart failure * Patient has history of malignant cancer, except certain skin or cervical cancers * Patient has a history of grand mal seizures within the last 6 months * Patient is pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of of Participants With Composite Events of Injection Site Reactions | 16 Weeks |
| Change From Baseline in Hemoglobin Level at Week 4 | 4 weeks |
| Number of Participants With Composite Events of Death, Myocardial Infarction and Cerebrovascular Accident, Serious Events of Unstable Angina, Transient Ischemic Attack, Arrythmia and Congestive Heart Failure, Peripheral Thrombo-embolic Events | 16 Weeks |
| Number of Participants With Composite Events of Transfusion-related Adverse Experiences | 16 Weeks |
| Number of Participants With Confirmed, Treatment Emergent Antibodies to MK2578 | 16 Weeks |
| Number of Participants With Hypertension, Seizure, and Pure Red Cell Aplasia | 16 Weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin Level | Weeks 1-3, 5-10, and Week 12 | — |
| Number of Participants Who Were Responders | Each week up to 12 weeks | Responder was defined as a participant achieving (pre-transfusion) an increase from baseline hemoglobin of greater than or equal to 1 g/dL and a hemoglobin concentration of greater than or equal to 11 g/dL. |
| Hemoglobin Concentration After Treatment With MK2578 | Weeks 1-10 and Week 12 | — |
Participant flow
Pre-assignment details
Participants in Cohorts 1 and 2 were to receive 1.0 mcg/kg/month and 2.0 mcg/kg/month, respectively, of MK2578. Participants in Cohort 3 were to be randomized to MK2578 3.6 mcg/kg/month or to weekly doses of darbepoetin alfa 0.45 mcg/kg/week. Cohort 1 was the only cohort initiated.
Participants by arm
| Arm | Count |
|---|---|
| MK2578 MK2578 1.0 mcg/kg given subcutaneously (SC) every month. | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study terminated by sponsor | 6 |
Baseline characteristics
| Characteristic | MK2578 |
|---|---|
| Age, Continuous | 60.9 years STANDARD_DEVIATION 5.01 |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Change From Baseline in Hemoglobin Level at Week 4
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MK2578 | Change From Baseline in Hemoglobin Level at Week 4 | Baseline Hemoglobin | 9.3 g/dL | Standard Deviation 0.4 |
| MK2578 | Change From Baseline in Hemoglobin Level at Week 4 | Change from Baseline in Hemoglobin at Week 4 | 0.5 g/dL | Standard Deviation 0.4 |
Primary
Number of of Participants With Composite Events of Injection Site Reactions
Time frame: 16 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK2578 | Number of of Participants With Composite Events of Injection Site Reactions | 1 Participants |
Primary
Number of Participants With Composite Events of Death, Myocardial Infarction and Cerebrovascular Accident, Serious Events of Unstable Angina, Transient Ischemic Attack, Arrythmia and Congestive Heart Failure, Peripheral Thrombo-embolic Events
Time frame: 16 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK2578 | Number of Participants With Composite Events of Death, Myocardial Infarction and Cerebrovascular Accident, Serious Events of Unstable Angina, Transient Ischemic Attack, Arrythmia and Congestive Heart Failure, Peripheral Thrombo-embolic Events | 0 Participants |
Primary
Number of Participants With Composite Events of Transfusion-related Adverse Experiences
Time frame: 16 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK2578 | 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: 16 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK2578 | Number of Participants With Confirmed, Treatment Emergent Antibodies to MK2578 | NA Participants |
Primary
Number of Participants With Hypertension, Seizure, and Pure Red Cell Aplasia
Time frame: 16 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MK2578 | Number of Participants With Hypertension, Seizure, and Pure Red Cell Aplasia | Hypertension | 1 Participants |
| MK2578 | Number of Participants With Hypertension, Seizure, and Pure Red Cell Aplasia | Seizure | 0 Participants |
| MK2578 | Number of Participants With Hypertension, Seizure, and Pure Red Cell Aplasia | Pure red cell aplasia | 0 Participants |
Secondary
Change From Baseline in Hemoglobin Level
Time frame: Weeks 1-3, 5-10, and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MK2578 | Change From Baseline in Hemoglobin Level | Change from Baseline in Hemoglobin at Week 1 (n=6) | -0.1 g/dL | Standard Deviation 0.6 |
| MK2578 | Change From Baseline in Hemoglobin Level | Change from Baseline in Hemoglobin at Week 2 (n=5) | 0.5 g/dL | Standard Deviation 0.4 |
| MK2578 | Change From Baseline in Hemoglobin Level | Change from Baseline in Hemoglobin at Week 3 (n=5) | 0.6 g/dL | Standard Deviation 0.7 |
| MK2578 | Change From Baseline in Hemoglobin Level | Change from Baseline in Hemoglobin at Week 5 (n=5) | 0.9 g/dL | Standard Deviation 0.4 |
| MK2578 | Change From Baseline in Hemoglobin Level | Change from Baseline in Hemoglobin at Week 6 (n=4) | 1.0 g/dL | Standard Deviation 0.6 |
| MK2578 | Change From Baseline in Hemoglobin Level | Change from Baseline in Hemoglobin at Week 7 (n=3) | 1.3 g/dL | Standard Deviation 0.7 |
| MK2578 | Change From Baseline in Hemoglobin Level | Change from Baseline in Hemoglobin at Week 8 (n=4) | 1.6 g/dL | Standard Deviation 0.4 |
| MK2578 | Change From Baseline in Hemoglobin Level | Change from Baseline in Hemoglobin at Week 9 (n=2) | 1.5 g/dL | Standard Deviation 0.1 |
| MK2578 | Change From Baseline in Hemoglobin Level | Change from Baseline in Hemoglobin at Week 10(n=1) | 1.6 g/dL | — |
| MK2578 | Change From Baseline in Hemoglobin Level | Change from Baseline in Hemoglobin at Week 12(n=1) | 2.1 g/dL | — |
Secondary
Hemoglobin Concentration After Treatment With MK2578
Time frame: Weeks 1-10 and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MK2578 | Hemoglobin Concentration After Treatment With MK2578 | Week 1 (n=6) | 9.2 g/dL | Standard Deviation 0.8 |
| MK2578 | Hemoglobin Concentration After Treatment With MK2578 | Week 2 (n=5) | 9.8 g/dL | Standard Deviation 0.6 |
| MK2578 | Hemoglobin Concentration After Treatment With MK2578 | Week 3 (n=5) | 9.9 g/dL | Standard Deviation 0.7 |
| MK2578 | Hemoglobin Concentration After Treatment With MK2578 | Week 4 (n=7) | 9.8 g/dL | Standard Deviation 0.6 |
| MK2578 | Hemoglobin Concentration After Treatment With MK2578 | Week 5 (n=5) | 10.3 g/dL | Standard Deviation 0.7 |
| MK2578 | Hemoglobin Concentration After Treatment With MK2578 | Week 6 (n=4) | 10.4 g/dL | Standard Deviation 0.8 |
| MK2578 | Hemoglobin Concentration After Treatment With MK2578 | Week 7 (n=3) | 10.8 g/dL | Standard Deviation 0.9 |
| MK2578 | Hemoglobin Concentration After Treatment With MK2578 | Week 8 (n=4) | 11.1 g/dL | Standard Deviation 0.7 |
| MK2578 | Hemoglobin Concentration After Treatment With MK2578 | Week 9 (n=2) | 10.9 g/dL | Standard Deviation 0.4 |
| MK2578 | Hemoglobin Concentration After Treatment With MK2578 | Week 10 (n=1) | 10.6 g/dL | — |
| MK2578 | Hemoglobin Concentration After Treatment With MK2578 | Week 12 (n=1) | 11.1 g/dL | — |
Secondary
Number of Participants Who Were Responders
Responder was defined as a participant achieving (pre-transfusion) an increase from baseline hemoglobin of greater than or equal to 1 g/dL and a hemoglobin concentration of greater than or equal to 11 g/dL.
Time frame: Each week up to 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK2578 | Number of Participants Who Were Responders | 4 Participants |