Evaluation of Two Epoetin Alfa Dosing Strategies in Subjects With Chronic Kidney Disease Receiving Hemodialysis

Study Overview
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Brief Summary
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The purpose of this study is to compare two different dosing methods of epoetin alfa and their effectiveness in maintaining hemoglobin levels between 10.0 to 11.0 g/dL in in patients with chronic kidney disease (CKD) receiving hemodialysis.

Official Title
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A Randomized, Multicenter, Double-blind Study Evaluating Two Epoetin Alfa Dosing Strategies in Subjects With Chronic Kidney Disease Receiving Hemodialysis

Conditions
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Anemia, Renal Insufficiency, Chronic, Renal Dialysis, Erythrocyte Transfusion

Intervention / Treatment
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* Drug: Epoetin alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained prior to initiation of any study-specific activities/procedures Age 18 or older Prescribed hemodialysis three times a week (TIW) for ≥ 12 weeks prior to randomization Prescribed IV administration of epoetin alfa TIW for ≥ 12 weeks prior to randomization Prescribed ≥ 3000 Units/week (ie, ≥ 1000 Units/administration) and < 90,000 Units/week (ie, < 30,000 Units/administration) of epoetin alfa during the 4 weeks prior to randomization Received ≥ 4 doses of epoetin alfa during the 2 weeks prior to randomization Hemoglobin concentration ≤ 11.0 g/dL, per the most recent local laboratory value obtained during the 2 weeks prior to randomization Hemoglobin concentration ≤ 11.0 g/dL, at the screening visit, using the hemoglobin point of care device provided by Amgen Iron replete, defined as a transferrin saturation (TSAT) ≥ 20% and a ferritin ≥ 100 ng/mL, per the most recent local laboratory value obtained during the 4 weeks prior to randomization Exclusion Criteria: Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s) prior to randomization Other investigational procedures while participating in this study are excluded Systemic hematologic disease (eg, sickle cell anemia, myelodysplastic syndrome, hematologic malignancy) Current or prior malignancy within 5 years of randomization, with the exception of non-melanoma skin cancers, cervical or breast ductal carcinoma in situ Treatment for any malignancy (eg, radiation, chemotherapy, hormone therapy or biologics) within 5 years of randomization, with the exception of locally excised non-melanoma skin cancers, cervical or breast ductal carcinoma in situ Subject is currently pregnant or planning to become pregnant during treatment and for 30 days after the end of treatment Subject is currently breast feeding or planning on breast feeding during treatment and for 30 days after the end of treatment Females of reproductive potential who are not willing to use an acceptable method of effective contraception during treatment and for at least 30 days after the end of treatment Currently receiving IV antibiotics Currently receiving systemic immunosuppressive therapy known to cause anemia, including treatment for active hepatitis (eg, azathioprine, mycophenolate mofetil, ≥ 10 mg prednisone [or equivalent]/day, interferon) Known human immunodeficiency virus (HIV) positive Known neutralizing anti-erythropoietic protein antibodies Known sensitivity to epoetin alfa Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, planned vacations where away from dialysis unit for more than 2 weeks) to the best of the subject and investigator's knowledge History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion Previously entered this study Occurrence of any of the following within 8 weeks prior to randomization: Seizure Clinically relevant active bleeding (eg, gastrointestinal bleed) RBC transfusion Any hospitalization or observational stay > 24 hours Uncontrolled hypertension, per the investigator within the 4 weeks prior to randomization Expected or scheduled solid organ transplant(eg, kidney) within 40 weeks after randomization Expected or scheduled to change dialysis modality (eg, peritoneal dialysis, home hemodialysis) within 40 weeks after randomization

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epoetin alfa Alternative Titration<br>Participants received epoetin alfa administered intravenously three times a week during hemodialysis for up to 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose changes may have occurred every 2 weeks according to the alternative dosing algorithm, where smaller, frequent dose adjustments were permitted based on six hemoglobin categories. | Drug: Epoetin alfa<br>* Administered intravenously (IV) three times a week (TIW) by appropriately trained healthcare professionals during hemodialysis.<br>* Other names: Epogen;|
| Active Comparator: Epoetin alfa USPI Titration<br>Participants received epoetin alfa administered intravenously three times a week during hemodialysis for 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose decreases were permitted every 2 weeks and beginning at week 5 dose increases could only occur ≥ 4 weeks from the last dose increase, according to the United States package insert (USPI) dosing algorithm which includes four categories of hemoglobin levels. | Drug: Epoetin alfa<br>* Administered intravenously (IV) three times a week (TIW) by appropriately trained healthcare professionals during hemodialysis.<br>* Other names: Epogen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Hemoglobin Measurements Within 10 to 11 g/dL During the Evaluation Period | Hemoglobin was measured every 2 weeks during the evaluation period. The percentage of these measurements that were within the range of 10-11 g/dL was calculated for each participant. | The evaluation period (weeks 13-37) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin Concentration at Each Visit |  | Baseline (screening visit) and weeks 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37 | 
| Percentage of Participants With Transfusion Events Overall and During Each Study Period | The percentage of participants who received red blood cell (RBC) transfusions during the study and during each study period. | Overall Study: Study week 1 to week 41; Titration Period: Study week 1 to week 12; Evaluation Period: Study week 13 to week 37; Safety Follow-up Period: Study week 38 to week 41 | 
| Hemoglobin Rate of Change at Each Visit | Hemoglobin rate of change (ROC) was calculated for each visit using the following formula: ROC = (current visit hemoglobin value - previous visit hemoglobin value) / number of days between each visit * 14. A positive value indicates a rate of rise and a negative value indicates a rate of decline. | Baseline (screening visit) and weeks 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37 | 
| Hemoglobin Intra-subject Variability | Intra-subject variability was defined for each participant as the standard deviation (SD) of all of the hemoglobin concentrations during the evaluation period for the participant. The mean intra-subject SD for all participants is the sum of the intra-subject SDs divided by the total number of participants evaluated. | The evaluation period (weeks 13 to 37) | 
| Percentage of Participants With Hemoglobin Excursions at Each Visit | An excursion is identified as an event when a hemoglobin concentration fell below or exceeded the pre-specified thresholds of: - < 9.0 g/dL, or - > 11.0 g/dL, or - > 12.0 g/dL. The percentage of participants with any excursions and excursions in each subcategory at each time point and overall during the study are reported. | Baseline (screening visit) and weeks 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37 | 
| Weekly Epoetin Alfa Dose at Each Visit |  | Weeks 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35 | 
| Number of RBC Units Transfused Overall and During Each Study Period | The number of red blood cell (RBC) units transfused during the study and during each study period. | Overall Study: Study week 1 to week 41; Titration Period: Study week 1 to week 12; Evaluation Period: Study week 13 to week 37; Safety Follow-up Period: Study week 38 to week 41 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anemia, Chronic Kidney Disease, Hemodialysis, Red Blood Cell Transfusion