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

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency, Chronic; Anemia; Renal Dialysis; Erythrocyte Transfusion
• Intervention / Treatment: Drug: Epoetin alfa

• Study Type: Interventional
• Enrollment (Actual): 216
• Phase: Phase 4

Contacts and Locations

Study Locations

• Puerto Rico
  • Toa Baja, Puerto Rico, 00949
    • Research Site
• United States
  • California
    • Cerritos, California, United States, 90703
      • Research Site
    • Glendale, California, United States, 91204
      • Research Site
    • Los Angeles, California, United States, 90022
      • Research Site
    • Los Angeles, California, United States, 90057
      • Research Site
    • Montebello, California, United States, 90640
      • Research Site
    • Riverside, California, United States, 92501
      • Research Site
    • San Diego, California, United States, 92115
      • Research Site
    • Simi Valley, California, United States, 93065
      • Research Site
    • Vacaville, California, United States, 95687
      • Research Site
    • Whittier, California, United States, 90606
      • Research Site
  • Florida
    • Miami, Florida, United States, 33150
      • Research Site
    • Miami Gardens, Florida, United States, 33169
      • Research Site
    • Pembroke Pines, Florida, United States, 33025
      • Research Site
  • Georgia
    • Macon, Georgia, United States, 31217
      • Research Site
    • Statesboro, Georgia, United States, 30458
      • Research Site
  • Indiana
    • Merrillville, Indiana, United States, 46410
      • Research Site
    • Michigan City, Indiana, United States, 46360
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Research Site
    • Pontiac, Michigan, United States, 48341
      • Research Site
    • Roseville, Michigan, United States, 48066
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Research Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Research Site
  • New York
    • Astoria, New York, United States, 11102
      • Research Site
    • Brooklyn, New York, United States, 11235
      • Research Site
    • Rosedale, New York, United States, 11422
      • Research Site
    • The Bronx, New York, United States, 10461
      • Research Site
  • North Carolina
    • Carrboro, North Carolina, United States, 27510
      • Research Site
    • Wilmington, North Carolina, United States, 28401
      • Research Site
  • Pennsylvania
    • Meadville, Pennsylvania, United States, 16335
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19106
      • Research Site
  • Texas
    • Houston, Texas, United States, 77070
      • Research Site
    • Houston, Texas, United States, 77004
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Research Site
  • Virginia
    • Hampton, Virginia, United States, 23666
      • Research Site
    • Norfolk, Virginia, United States, 23502
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Epoetin alfa Alternative Titration; 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; Administered intravenously (IV) three times a week (TIW) by appropriately trained healthcare professionals during hemodialysis.; Other Names: Epogen
Active Comparator: Epoetin alfa USPI Titration; 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; Administered intravenously (IV) three times a week (TIW) by appropriately trained healthcare professionals during hemodialysis.; Other Names: Epogen

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): April 27, 2016
• Study Completion (Actual): May 25, 2016

Study Registration Dates

• First Submitted: September 11, 2014
• First Submitted That Met QC Criteria: September 29, 2014
• First Posted (Estimate): October 1, 2014

Study Record Updates

• Last Update Posted (Actual): May 19, 2017
• Last Update Submitted That Met QC Criteria: May 18, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Anemia; Chronic Kidney Disease; Hemodialysis; Red Blood Cell Transfusion
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Hematinics; Epoetin Alfa
• Other Study ID Numbers: 20110208