Anemia, Chronic Kidney Disease, Chronic Renal Failure, Pure Red Cell Aplasia
Conditions
Keywords
Drug Therapy, pure red cell aplasia, PRCA, chronic kidney disease, CKD, chronic renal failure, CRF, anemia, erythropoietin, EPO, erythropoiesis stimulating agent, ESA, hemoglobin, Hb, Hgb, red blood cell, red blood cell production
Brief summary
The purpose of this study is to evaluate the ability of peginesatide (AF37702) to increase and maintain increased hemoglobin levels in participants with chronic kidney disease (CKD) (either not on dialysis, receiving regular hemodialysis or peritoneal dialysis, or following renal transplant) with confirmed antibody-mediated pure red cell aplasia (PRCA).
Detailed description
The drug being tested in this study was peginesatide. Peginesatide injection was tested to investigate the efficacy and safety in the treatment of anemia caused by antibody-mediated pure red cell aplasia in participants with chronic kidney disease. The study enrolled 22 patients. All the participants enrolled into the study received: • Peginesatide 0.5 mg/kg subcutaneous (SC) injection The participants received a starting dose of 0.05 mg/kg (every 4 weeks) followed by 0.1 mg/kg dose, based on the assessment of the dose response in the initial group of 5 participants. The frequency of each injection and the dose adjusted based on the participant's hemoglobin response and the ability to maintain a hemoglobin level in the range of 10.0-12.0 g/dL. This multi-center trial was conducted in Europe. The overall time to participate in this study was 10 years and 7 months approximately. Participants made multiple visits to the clinic until the projected end of treatment period, which was 31-Oct-2016.
Interventions
DRUGPeginesatide
Peginesatide injection
Sponsors
Takeda
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
* Participants who have confirmed antibody-mediated Pure red cell aplasia (PRCA) are potentially eligible for enrollment into this study. * Participants must be ≥ 18 years old at the time of consent. * Erythropoiesis stimulating agents (ESAs) must be discontinued for a minimum of 1 month prior to screening. * Participant requires periodic transfusions to maintain hemoglobin. * Hemoglobin \< 10 g/dL for at least 2 measurements or participant has received a transfusion within the past 4 weeks to achieve a hemoglobin \> 10 g/dL. * Confirmation that an anti-erythropoietin antibody sample was obtained for analysis by the central reference laboratory within 1 month prior to baseline. * Participants can either be participants with chronic kidney disease not yet requiring renal replacement therapy (participants not on dialysis), those on regular hemodialysis or peritoneal dialysis, or following a renal transplant. * Participants may or may not have previously been treated with immunosuppressive therapy. * Pre-menopausal females (with the exception of those who are surgically sterile) must have a negative pregnancy test at screening. * Written informed consent must be obtained.
Exclusion criteria
* Participants already successfully on another erythropoietic agent. * Abnormal bone marrow findings consistent with the diagnosis of myelodysplasia, a myeloproliferative disorder, hematologic malignancy or evidence of metastatic infiltration. * Poorly controlled hypertension. * Previous exposure to any investigational agent within 4 weeks prior to administration of study drug or planned receipt during the study period. * High likelihood of early withdrawal or interruption of the study. * Participants who refuse to give informed consent. * Women who are pregnant, lactating or not using a medically approved birth control. * Life expectancy \<12 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced Increase and Maintain Hemoglobin Levels (Two Consecutive Values) Greater Than or Equal to the Lower Limit of the Target Range in the Absence of Red Blood Cell Transfusion in the Previous 28 Days by Week 24 | Up to Week 24 | Percentage of participants who experienced increase and maintain hemoglobin levels (two consecutive values) greater than or equal to the lower limit (11 g/dL) in the absence of red blood cell transfusion in the previous 28 days by week 24 were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Red Blood Cells (RBCs) Transfusions During the 26 Weeks Pre-treatment Period (Prior to Enrollment) and During 13- and 26 Weeks Intervals During the Study | 26 weeks prior to enrollment up to end of study (up to 60 months) | — |
| Percentage of Participants With RBC Transfusions During the 26-week Pre-treatment Period and During 13- and 26-week Intervals During the Study | 26 weeks prior to enrollment up to end of study (up to 60 months) | — |
| Time to Initial Achievement of Hemoglobin (Hgb) Greater Than or Equal to the Lower Limit of the Target Range in the Absence of Red Blood Cell Transfusions in the Previous 28 Days | Up to 60 months | The time between first dose administered and the initial achievement of a Hgb increase ≥11 g/dL for two consecutive visits was calculated for each participant as the number of days between the first dose administration date and the earlier of (1) the study termination date \[i.e. censor date\] and (2) the first date of an Hgb increase ≥ 11 g/dL for two consecutive visits without whole blood or RBC transfusion during the previous 28 days. Time to initial Hgb increase ≥ 11 g/dL will be calculated for each participant as the minimum of censor date and increase date minus the first dose date plus 1. |
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Treatment Discontinuation | From signing of informed consent form up to Month 60 | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. |
Countries
France, Germany, United Kingdom
Participant flow
Recruitment details
Participants took part in the study at 5 investigative sites in Europe from 06-Apr-2006 to 31-Oct-2016.
Pre-assignment details
Participants with a diagnosis of chronic renal failure (CRF) with confirmed antibody-mediated pure red cell aplasia (PRCA) were enrolled to receive peginesatide subcutaneous injection up to 0.3 mg/kg, once every 4 weeks for up to 60 months.
Participants by arm
| Arm | Count |
|---|---|
| Peginesatide Peginesatide 0.05 mg/kg injection, subcutaneously followed by peginesatide 0.1 mg/kg injection, subcutaneously once every 4 weeks for up to 60 months.
Individual dose of peginesatide injection was modified based on hemoglobin levels. Dose adjustments were made in order to achieve and maintain hemoglobin in the target range of 10.0-12.0 g/dL. | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 8 |
| Overall Study | Death | 4 |
| Overall Study | Participants Withdrew Consent | 2 |
| Overall Study | Reason not Specified | 3 |
| Overall Study | Renal Transplant | 3 |
Baseline characteristics
| Characteristic | Peginesatide |
|---|---|
| Age, Continuous | 73.3 years STANDARD_DEVIATION 13.65 |
| Baseline Anti-erythropoietin (EPO) Antibody Titers | 94.1 U/mL STANDARD_DEVIATION 217.08 |
| Baseline Ferritin | 2332.0 ug/L STANDARD_DEVIATION 1695.02 |
| Baseline Hemoglobin (Hgb) | 96.5 g/L STANDARD_DEVIATION 16.11 |
| Baseline Transferrin Saturation | 79.2 % transferrin STANDARD_DEVIATION 21.87 |
| Body Mass Index (BMI) | 23.8 kg/m^2 STANDARD_DEVIATION 2.41 |
| Bone Marrow Evaluation Aplasia of Erythropoese | 1 Participants |
| Bone Marrow Evaluation EBP 0% normal values for other cell lineages | 1 Participants |
| Bone Marrow Evaluation Erythroblastopenia (EBP) | 1 Participants |
| Bone Marrow Evaluation Erythroid series absent | 1 Participants |
| Bone Marrow Evaluation Erythroid severe HYP no decrease in other lineages | 1 Participants |
| Bone Marrow Evaluation Erythropoietic hypoplasia | 1 Participants |
| Bone Marrow Evaluation Hpc BM with reduced EL consistent with dgn of pure | 1 Participants |
| Bone Marrow Evaluation HYP of erythropoiesis staining of iron in BM retic | 1 Participants |
| Bone Marrow Evaluation Normal | 1 Participants |
| Bone Marrow Evaluation PRCA | 8 Participants |
| Bone Marrow Evaluation PRCA / Bone Marrow Trephine | 1 Participants |
| Bone Marrow Evaluation Pure Red Cell Aplasia | 2 Participants |
| Bone Marrow Evaluation Red cell aplasia | 1 Participants |
| Bone Marrow Evaluation Red cell hypoplasia | 1 Participants |
| Height | 168.1 cm STANDARD_DEVIATION 9.66 |
| Race/Ethnicity, Customized Asian | 4 Participants |
| Race/Ethnicity, Customized Caucasian | 17 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Region of Enrollment France | 6 Participants |
| Region of Enrollment Germany | 8 Participants |
| Region of Enrollment United Kingdom | 8 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 17 Participants |
| Weight | 67.6 kg STANDARD_DEVIATION 12.31 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 22 |
| serious Total, serious adverse events | 17 / 22 |
Outcome results
Primary
Percentage of Participants Who Experienced Increase and Maintain Hemoglobin Levels (Two Consecutive Values) Greater Than or Equal to the Lower Limit of the Target Range in the Absence of Red Blood Cell Transfusion in the Previous 28 Days by Week 24
Percentage of participants who experienced increase and maintain hemoglobin levels (two consecutive values) greater than or equal to the lower limit (11 g/dL) in the absence of red blood cell transfusion in the previous 28 days by week 24 were reported.
Time frame: Up to Week 24
Population: Efficacy endpoint data was not collected due to low patient enrollment and the drug was withdrawn from the market.
Secondary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Treatment Discontinuation
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: From signing of informed consent form up to Month 60
Population: Safety analysis set included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Peginesatide | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Treatment Discontinuation | AEs Leading to Study Drug Discontinuation | 3 Participants |
| Peginesatide | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Treatment Discontinuation | AEs | 22 Participants |
| Peginesatide | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Treatment Discontinuation | SAEs | 17 Participants |
Secondary
Number of Red Blood Cells (RBCs) Transfusions During the 26 Weeks Pre-treatment Period (Prior to Enrollment) and During 13- and 26 Weeks Intervals During the Study
Time frame: 26 weeks prior to enrollment up to end of study (up to 60 months)
Population: Efficacy endpoint data was not collected due to low patient enrollment and the drug was withdrawn from the market.
Secondary
Percentage of Participants With RBC Transfusions During the 26-week Pre-treatment Period and During 13- and 26-week Intervals During the Study
Time frame: 26 weeks prior to enrollment up to end of study (up to 60 months)
Population: Efficacy endpoint data was not collected due to low patient enrollment and the drug was withdrawn from the market.
Secondary
Time to Initial Achievement of Hemoglobin (Hgb) Greater Than or Equal to the Lower Limit of the Target Range in the Absence of Red Blood Cell Transfusions in the Previous 28 Days
The time between first dose administered and the initial achievement of a Hgb increase ≥11 g/dL for two consecutive visits was calculated for each participant as the number of days between the first dose administration date and the earlier of (1) the study termination date \[i.e. censor date\] and (2) the first date of an Hgb increase ≥ 11 g/dL for two consecutive visits without whole blood or RBC transfusion during the previous 28 days. Time to initial Hgb increase ≥ 11 g/dL will be calculated for each participant as the minimum of censor date and increase date minus the first dose date plus 1.
Time frame: Up to 60 months
Population: Efficacy endpoint data was not collected due to low patient enrollment and the drug was withdrawn from the market.