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

• ClinicalTrials.gov Identifier: NCT02253654
• Recruitment Status: Completed
• First Posted: October 1, 2014
• Results First Posted: May 12, 2017
• Last Update Posted: May 19, 2017
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Renal Insufficiency, Chronic; Anemia; Renal Dialysis; Erythrocyte Transfusion	Drug: Epoetin alfa	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 216 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Multicenter, Double-blind Study Evaluating Two Epoetin Alfa Dosing Strategies in Subjects With Chronic Kidney Disease Receiving Hemodialysis
• Actual Study Start Date: April 1, 2015
• Actual Primary Completion Date: April 27, 2016
• Actual Study Completion Date: May 25, 2016

Arms and Interventions

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 Name: 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 Name: Epogen

Outcome Measures

Primary Outcome Measures :

1. Percentage of Hemoglobin Measurements Within 10 to 11 g/dL During the Evaluation Period [ Time Frame: The evaluation period (weeks 13-37) ]
   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.

Secondary Outcome Measures :

1. Hemoglobin Concentration at Each Visit [ Time Frame: Baseline (screening visit) and weeks 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37 ]
2. Percentage of Participants With Transfusion Events Overall and During Each Study Period [ Time Frame: 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 ]
   The percentage of participants who received red blood cell (RBC) transfusions during the study and during each study period.
3. Hemoglobin Rate of Change at Each Visit [ Time Frame: 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 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.
4. Hemoglobin Intra-subject Variability [ Time Frame: The evaluation period (weeks 13 to 37) ]
   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.
5. Percentage of Participants With Hemoglobin Excursions at Each Visit [ Time Frame: Baseline (screening visit) and weeks 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37 ]
   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.
6. Weekly Epoetin Alfa Dose at Each Visit [ Time Frame: Weeks 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35 ]
7. Number of RBC Units Transfused Overall and During Each Study Period [ Time Frame: 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 ]
   The number of red blood cell (RBC) units transfused during the study and during each study period.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Research Site

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

United States, Florida

Research Site

Miami Gardens, Florida, United States, 33169

Research Site

Miami, Florida, United States, 33150

Research Site

Pembroke Pines, Florida, United States, 33025

United States, Georgia

Research Site

Macon, Georgia, United States, 31217

Research Site

Statesboro, Georgia, United States, 30458

United States, Indiana

Research Site

Merrillville, Indiana, United States, 46410

Research Site

Michigan City, Indiana, United States, 46360

United States, Michigan

Research Site

Detroit, Michigan, United States, 48202

Research Site

Pontiac, Michigan, United States, 48341

Research Site

Roseville, Michigan, United States, 48066

United States, Missouri

Research Site

Kansas City, Missouri, United States, 64111

United States, Nebraska

Research Site

Lincoln, Nebraska, United States, 68510

United States, New York

Research Site

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

United States, North Carolina

Research Site

Carrboro, North Carolina, United States, 27510

Research Site

Wilmington, North Carolina, United States, 28401

United States, Pennsylvania

Research Site

Meadville, Pennsylvania, United States, 16335

Research Site

Philadelphia, Pennsylvania, United States, 19106

United States, Texas

Research Site

Houston, Texas, United States, 77004

Research Site

Houston, Texas, United States, 77070

Research Site

San Antonio, Texas, United States, 78229

United States, Vermont

Research Site

Burlington, Vermont, United States, 05401

United States, Virginia

Research Site

Hampton, Virginia, United States, 23666

Research Site

Norfolk, Virginia, United States, 23502

Puerto Rico

Research Site

Toa Baja, Puerto Rico, 00949

Sponsors and Collaborators

Amgen

Investigators

• Study Director: MD; Amgen

More Information

Additional Information:

AmgenTrials clinical trials website 

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02253654
• Other Study ID Numbers: 20110208
• First Posted: October 1, 2014
• Results First Posted: May 12, 2017
• Last Update Posted: May 19, 2017
• Last Verified: May 2017

Keywords provided by Amgen:

Chronic Kidney Disease; Anemia; Hemodialysis; Red Blood Cell Transfusion

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Urologic Diseases; Epoetin Alfa; Hematinics