Anemia, Chronic Kidney Disease, Chronic Renal Failure
Conditions
Keywords
anemia, chronic kidney disease, CKD, chronic renal failure, CRF, dialysis, erythropoietin, EPO, erythropoiesis stimulating agent, ESA, Hematide™, hemodialysis, hemoglobin, Hb, Hgb, Omontys, peginesatide, red blood cell, red blood cell production
Brief summary
The purpose of this study was to evaluate the long term safety and tolerability of peginesatide for the maintenance of hemoglobin in participants with chronic kidney disease (CKD) who had received at least 24 weeks of peginesatide treatment in an earlier study.
Detailed description
Anemia associated with chronic kidney disease is due to several factors, primarily the inability of the diseased kidneys to produce adequate amounts of endogenous erythropoietin. Ancillary factors include the shortened lifespan of red blood cells, iron and other nutritional deficiencies, infection, and inflammation. The presence and severity of anemia are related to the duration and extent of kidney failure. Anemia is associated with increased mortality, increased likelihood of hospitalization, reduced cognitive function, and increased left ventricular hypertrophy and heart failure. Erythropoiesis stimulating agents (ESAs) have been established as a treatment for anemia in subjects with chronic kidney disease, and have improved the management of anemia over alternatives such as transfusion. Peginesatide is a parenteral formulation developed for the treatment of anemia associated with chronic kidney disease. Peginesatide binds to and activates the human erythropoietin receptor, and stimulates erythropoiesis in human red cell precursors in a manner similar to other known erythropoiesis-stimulating agents. Study participants had received at least 24 weeks of peginesatide dosing in a previous Affymax-sponsored study and were to receive doses of peginesatide for up to 54 months. However, the Sponsor ended the study early.
Interventions
DRUGpeginesatide
Participants received the same initial peginesatide dose via the same route, intravenously or subcutaneously, as was administered at the end of the previous peginesatide treatment study in which the participant was enrolled. The median first dose at study start was 0.044 milligram per kilogram (mg/kg) with an interquartile range of 0.028 to 0.076 mg/kg. Each participant was to receive peginesatide as an injection administered once every 4 weeks for approximately 54 months in this trial.
Sponsors
Affymax
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant is informed of the investigational nature of this study and has given written, informed consent in accordance with institutional, local, and national guidelines. * Males or females ≥ 18 years of age. * Premenopausal females (with the exception of those who are surgically sterile) must have a negative pregnancy test at screening; those who are sexually active must practice a highly effective method of birth control for at least 4 weeks prior to study drug administration, and must be willing to continue contraception until at least 4 weeks after the last dose of study drug. * Participant who has received at least 24 weeks of peginesatide dosing in a previous Affymax-sponsored study. * One hemoglobin value of ≥ 10.0 grams per deciliter (g/dL) in the 4 weeks prior to study drug administration.
Exclusion criteria
* Known intolerance to peginesatide or pegylated products. * History of antibodies to any erythropoiesis stimulating agent (ESA) or history of pure red cell aplasia (PRCA). * High likelihood of early withdrawal or interruption of the study (e.g., participant suffers from any clinically significant medical disease or condition that may, in the Investigator's opinion, interfere with safety, assessment, or follow-up of the participant) * Anticipated life expectancy \< 18 months * Receipt of any ESA other than peginesatide at any time after participant enrollment in the previous Affymax-sponsored study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of Participants With Mean Hemoglobin in the Target Range of 10.0-12.0 Grams Per Deciliter (g/dL) After Final Dosing Guideline Change | Up to 54 months |
Countries
Bulgaria, Poland, Romania, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Maintenance Switch in Dialysis Participants Participants were from a prior Affymax peginesatide treatment study conducted in participants who were on dialysis and had been on Epoetin at study entry, and who were switched to peginesatide (NCT00434330). The median first dose at study start was 0.044 milligram per kilogram (mg/kg) with an interquartile range of 0.028 to 0.076 mg/kg. This group is categorized as Maintenance Switch in Dialysis Participants regardless of dialysis status at the start of or during this study. | 51 |
| Treatment Initiation in Non-Dialysis Participants Participants were from a prior Affymax peginesatide treatment study conducted in participants who were not on dialysis and not on erythropoiesis stimulating agents (ESAs), and who received peginesatide (NCT00228436). The median first dose at study start was 0.024 mg/kg with an interquartile range of 0.017 to 0.035 mg/kg. This group is categorized as Initiation of Treatment in Non-Dialysis Participants regardless of dialysis status at the start of or during this study. | 63 |
| Pooled AF37702 Inj. | 114 |
| Total | 228 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 9 |
| Overall Study | PI Decision | 0 | 2 |
| Overall Study | Relocation | 1 | 0 |
| Overall Study | Renal transplant | 1 | 1 |
| Overall Study | Site closed by sponsor | 3 | 0 |
| Overall Study | Sponsor Decision to Terminate Study | 35 | 30 |
| Overall Study | Withdrawal by Subject | 7 | 6 |
Baseline characteristics
| Characteristic | Maintenance Switch in Dialysis Participants | Treatment Initiation in Non-Dialysis Participants | Pooled AF37702 Inj. |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 41 Participants | 50 Participants |
| Age, Categorical Between 18 and 65 years | 42 Participants | 22 Participants | 64 Participants |
| Age Continuous | 53.2 years STANDARD_DEVIATION 11.92 | 66.4 years STANDARD_DEVIATION 13.48 | 60.5 years STANDARD_DEVIATION 14.36 |
| Sex: Female, Male Female | 19 Participants | 34 Participants | 53 Participants |
| Sex: Female, Male Male | 32 Participants | 29 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 46 / 51 | 55 / 63 |
| serious Total, serious adverse events | 10 / 51 | 31 / 63 |
Outcome results
Primary
Proportion of Participants With Mean Hemoglobin in the Target Range of 10.0-12.0 Grams Per Deciliter (g/dL) After Final Dosing Guideline Change
Time frame: Up to 54 months
Population: Full Analysis - Number of participants with hemoglobin assessed after dosing guideline change
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maintenance Switch in Dialysis Participants | Proportion of Participants With Mean Hemoglobin in the Target Range of 10.0-12.0 Grams Per Deciliter (g/dL) After Final Dosing Guideline Change | 0.786 percentage of participants |
| Treatment Initiation in Non-Dialysis Participants | Proportion of Participants With Mean Hemoglobin in the Target Range of 10.0-12.0 Grams Per Deciliter (g/dL) After Final Dosing Guideline Change | 0.875 percentage of participants |