Study to Compare Safety and Efficacy of HX575 Epoetin Alfa and US-licensed Epoetin Alfa (ACCESS)

Randomized, Double-blind, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of HX575 Epoetin Alfa vs. US Licensed Epoetin Alfa (Epogen®/Procrit®) in the Treatment of Anemia Associated With Chronic Kidney Disease

The purpose of this study is to show biosimilarity of HX575 epoetin alfa with the US licensed reference product Epogen®/Procrit® when applied subcutaneously. This study is intended to generate data supporting that the efficacy and safety under treatment with HX575 and Epogen®/Procrit® are comparable.

Study Overview

• Status: Completed
• Conditions: Anemia; Chronic Kidney Disease (CKD)
• Intervention / Treatment: Drug: HX575 epoetin alfa; Drug: US-licensed epoetin alfa

Detailed Description

This is a randomized, double-blind, parallel-group, multicenter study to evaluate the efficacy and safety of HX575 epoetin alfa vs. US-licensed epoetin alfa (Epogen®/Procrit®) in the treatment of anemia associated with chronic kidney disease (CKD).

• Study Type: Interventional
• Enrollment (Actual): 435
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85284
      • Southwestern Kidney Institute
  • California
    • Azusa, California, United States, 91702
      • North America Research Institute
    • Bakersfield, California, United States, 93308
      • Pegasus Dialysis, LLC
    • Bakersfield, California, United States, 93309
      • Central Nephrology Medical Group
    • Chula Vista, California, United States, 91910
      • California Institute of Renal Research
    • Granada Hills, California, United States, 91344
      • Renal Consultants Medical Group
    • Inglewood, California, United States, 90301
      • Angel Kidney Care of Inglewood Dialysis Center
    • La Mesa, California, United States, 91942
      • California Institute of Renal Research
    • Laguna Hills, California, United States, 92653
      • Alliance Research Centers
    • Los Angeles, California, United States, 90022
      • Academic Medical Research Institute
    • Los Angeles, California, United States, 90048
      • Tower Nephrology Medical Group
    • Los Angeles, California, United States, 90025
      • Ronald Reagan Medical Center, Department of Pharmaceutical Services, Drug Information Center
    • Los Angeles, California, United States, 90057
      • St Vincent Dialysis Center
    • Lynwood, California, United States, 90262
      • Kidney Research Center
    • Northridge, California, United States, 91324
      • Valley Renal Medical Group
    • Ontario, California, United States, 91762
      • Ontario Dialysis, Inc.
    • Riverside, California, United States, 92505
      • Apex Research of Riverside
    • Sacramento, California, United States, 95825
      • Capital Nephrology Medical Group
    • San Diego, California, United States, 92111
      • California Institute of Renal Research
    • San Diego, California, United States, 92154
      • La Jolla Clinical Research, Inc.
    • San Dimas, California, United States, 91773
      • North America Research Institute
    • Whittier, California, United States, 90603
      • American Institute of Research
  • Florida
    • Coral Springs, Florida, United States, 33071
      • South Florida Nephrology
    • Hollywood, Florida, United States, 33020
      • Pines Clinical Research Inc.
    • Tampa, Florida, United States, 33614
      • Genesis Clinical Research Corporation
  • Georgia
    • Statesboro, Georgia, United States, 30458
      • Atekha Nephrology Clinic LLC
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Four Rivers Clinical Research, Incorporated
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Northwest Louisana Nephrology
  • Maryland
    • Germantown, Maryland, United States, 20874
      • Germantown Dialysis
  • Missouri
    • Farmington, Missouri, United States, 63640
      • Fresenius Management Services, Inc.
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Creighton University
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Kidney Specialists of Southern Nevada
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • Seacoast Kidney and Hypertension Specialist, PLLC
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Renal Medicine Associates
  • New York
    • Fresh Meadows, New York, United States, 11365
      • New York Hospital Queens
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Metrolina Nephrology Associates, PA
    • Rocky Mount, North Carolina, United States, 27804
      • Boice-Willis Clinic, PA
    • Wilmington, North Carolina, United States, 28401
      • Southeastern Dialysis Center
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Northeast Clinical Research Centers, Inc.
    • Philadelphia, Pennsylvania, United States, 19118
      • Delaware Valley Nephrology and Hypertension Associates, PC
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • SC Nephrology & Hypertension Center, Inc.
    • Orangeburg, South Carolina, United States, 29118
      • Palmetto Nephrology Pa
  • Tennessee
    • Knoxville, Tennessee, United States, 37923
      • Knoxville Kidney Center PLLC
  • Texas
    • Austin, Texas, United States, 78756
      • Research Management, Inc.
    • Edinburg, Texas, United States, 78539
      • Gamma Clinical Research Institute
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • Houston, Texas, United States, 77030
      • Nephrology, P.A.
    • San Antonio, Texas, United States, 78215-2035
      • Renal Associates, PA
  • Utah
    • Saint George, Utah, United States, 84770
      • Southern Utah Kidney and Hypertension Center
  • Virginia
    • Alexandria, Virginia, United States, 22304
      • Mendez Center for Clinical Research, LLC
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Hospitals and Clinic

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:

• Patients with end stage renal disease (stage CKD 5d), receiving stable subcutaneous maintenance therapy with Epogen® or Procrit® at least once per week
• Mean hemoglobin level between 9.0 - 11.5 g/dL during the screening period
• Adequate iron substitution

Exclusion Criteria:

• Contraindications for Erythropoiesis Stimulating Agent (ESA) therapy
• History of Pure Red Cell Aplasia (PRCA), or anti-erythropoietin (EPO) antibodies
• Known Human Immunodeficiency Virus (HIV) or Hepatitis B infection
• Hepatitis C infection on an active treatment
• Symptomatic congestive heart failure (New York Heart Association [NYHA] class III and IV)
• Unstable angina pectoris, or cardiac infarction during the last 6 months prior to randomization
• Percutaneous coronary intervention, or coronary artery bypass grafting during the last 6 months prior to randomization
• History of malignancy of any organ system
• Systemic lupus erythematous
• Immunocompromized patients

Other In-/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HX575 epoetin alfa; HX575, recombinant human epoetin alfa	Drug: HX575 epoetin alfa; Solution for subcutaneous injection. The drug is administered subcutaneously at least once per week over 52 weeks. The dose will be individually titrated to maintain hemoglobin levels between 10 to 11 g/dL.; Other Names: Binocrit® (Europe); Epoetin alfa HEXAL® (Europe); Abseamed® (Europe)
Active Comparator: US-licensed epoetin alfa; US-licensed recombinant human epoetin alfa	Drug: US-licensed epoetin alfa; Solution for subcutaneous injection.; Other Names: Epogen®; Procrit®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Absolute Change in Hemoglobin Levels Between the Screening/Baseline Period (Week -4 to Day 1) and the Evaluation Period (Week 21-28)	Response to epoetin alfa in anemic patients with chronic renal failure is manifested by increased hematocrit, hemoglobin, reduced transfusion requirements and increase in quality of life. Hemoglobin (laboratory haematology parameter) is the primary endpoint of the study .	Week -4 to Day1 and Week 21-28
Change in Mean Hb Level Between Baseline (Week -4 to Day1) and Evaluation Period (Week 21-28)	Response to epoetin alfa in anemic patients with chronic renal failure is manifested by increased hematocrit, hemoglobin, reduced transfusion requirements and increase in quality of life. Hemoglobin (laboratory haematology parameter) is the primary endpoint of the study .	Week -4 to Day1 and Week 21-28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Weekly Dose During Evaluation Period (Week 21-28)	Mean weekly study drug dose during evaluation period (Week 21-28)	Week 21-28
Incidence of Antibody Formation Against Epoetin	Number of patients with positive antidrug antibody (ADA) finding at any time during their treatment period. Count includes 2 patients (1 in each arm) that already had a positive ADA Baseline finding. ADA testing performed by by Radio-Immuno-Precipitation assay. No patient developed neutralizing antibodies.	52 weeks

Collaborators and Investigators

• Sponsor: Sandoz
• Investigators: Study Director: Sandoz Biopharmaceutical Clinical Development, Sandoz Biopharmaceuticals

Publications and helpful links

General Publications

• Weir MR, Pergola PE, Agarwal R, Fink JC, Kopyt NP, Singh AK, Kumar J, Schmitt S, Schaffar G, Rudy A, McKay JP, Kanceva R. A Comparison of the Safety and Efficacy of HX575 (Epoetin Alfa Proposed Biosimilar) with Epoetin Alfa in Patients with End-Stage Renal Disease. Am J Nephrol. 2017;46(5):364-370. doi: 10.1159/000481736. Epub 2017 Oct 30.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: September 21, 2012
• First Submitted That Met QC Criteria: September 25, 2012
• First Posted (Estimate): September 26, 2012

Study Record Updates

• Last Update Posted (Actual): July 2, 2017
• Last Update Submitted That Met QC Criteria: June 1, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: erythropoietin alfa; CKD 5d
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Anemia; Hematinics; Epoetin Alfa
• Other Study ID Numbers: HX575-307

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED