Extension Study of Etelcalcetide for Treatment of Secondary Hyperparathyroidism in Patients With Chronic Kidney Disease on Hemodialysis

A Multicenter Single-arm Extension Study to Describe the Long-term Safety of AMG 416 in the Treatment of Secondary Hyperparathyroidism in Subjects With Chronic Kidney Disease on Hemodialysis

This is a multicenter, single-arm, extension study to characterize the long-term safety and tolerability of etelcalcetide in the treatment of Secondary Hyperparathyroidism (SHPT) in adults with Chronic Kidney Disease (CKD) on hemodialysis.

Study Overview

• Status: Completed
• Conditions: Hyperparathyroidism, Secondary
• Intervention / Treatment: Drug: Etelcalcetide

Detailed Description

This is a multicenter, single-arm, extension study in which adults with secondary hyperparathyroidism currently receiving hemodialysis and previously treated in Amgen studies 20120231 (NCT01785875), 20120334 (NCT01576146), or 20120360 (NCT01896232) will continue to be treated with etelcalcetide until approximately 2.5 years after the first participant was enrolled.

• Study Type: Interventional
• Enrollment (Actual): 902
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Research Site
    • Westmead, New South Wales, Australia, 2145
      • Research Site
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Research Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Research Site
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Research Site
    • Prahan, Victoria, Australia, 3004
      • Research Site
• Austria
  • Feldkirch, Austria, 6807
    • Research Site
  • Graz, Austria, 8036
    • Research Site
  • Linz, Austria, 4020
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  • Wien, Austria, 1090
    • Research Site
  • Wien, Austria, 1220
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• Belgium
  • Aalst, Belgium, 9300
    • Research Site
  • Baudour, Belgium, 7331
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  • Bonheiden, Belgium, 2820
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  • Brussels, Belgium, 1200
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  • Bruxelles, Belgium, 1020
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  • Hasselt, Belgium, 3500
    • Research Site
  • Kortrijk, Belgium, 8500
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  • Leuven, Belgium, 3000
    • Research Site
  • Liege, Belgium, 4000
    • Research Site
  • Liège, Belgium, 4000
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  • Roeselare, Belgium, 8800
    • Research Site
  • Tournai, Belgium, 7500
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• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Research Site
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Research Site
  • Newfoundland and Labrador
    • St. Johns, Newfoundland and Labrador, Canada, A1B 3V6
      • Research Site
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • Research Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Research Site
    • Montreal, Quebec, Canada, H4J 1C5
      • Research Site
• Czechia
  • Hradec Kralove, Czechia, 500 05
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  • Novy Jicin, Czechia, 741 01
    • Research Site
  • Plzen, Czechia, 301 00
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  • Praha 4, Czechia, 140 21
    • Research Site
  • Praha 4 - Nusle, Czechia, 140 00
    • Research Site
  • Praha 6, Czechia, 169 00
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  • Slavkov u Brna, Czechia, 684 01
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  • Usti nad Orlici, Czechia, 562 18
    • Research Site
• Denmark
  • Fredericia, Denmark, 7000
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  • København, Denmark, 2100
    • Research Site
• France
  • Caen, France, 14000
    • Research Site
  • La Tronche cedex, France, 38701
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  • Lille Cedex, France, 59800
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  • Marseille, France, 13253
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  • Paris, France, 75014
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  • Paris, France, 75011
    • Research Site
  • Reims Cedex, France, 51092
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  • Saint Priest en Jarez, France, 42270
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  • Saint-Ouen, France, 93400
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• Germany
  • Aachen, Germany, 52074
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  • Berlin, Germany, 12053
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  • Hamburg, Germany, 22297
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  • Langenhagen, Germany, 30853
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  • Minden, Germany, 32429
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  • München, Germany, 81675
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  • Villingen-Schwenningen, Germany, 78052
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  • Wiesbaden, Germany, 65191
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  • Zwickau, Germany, 08060
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• Greece
  • Alexandroupoli, Greece, 68100
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  • Larissa, Greece, 41110
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  • Nikaia, Piraeus, Greece, 18454
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  • Patra, Greece, 26500
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  • Thessaloniki, Greece, 54636
    • Research Site
• Hungary
  • Baja, Hungary, 6500
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  • Budapest, Hungary, 1106
    • Research Site
  • Esztergom, Hungary, 2500
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  • Gyor, Hungary, 9023
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  • Kaposvar, Hungary, 7400
    • Research Site
  • Kistarcsa, Hungary, 2143
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  • Miskolc, Hungary, 3526
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  • Pecs, Hungary, 7624
    • Research Site
  • Pecs, Hungary, 7633
    • Research Site
  • Szekesfehervar, Hungary, 8000
    • Research Site
  • Szigetvar, Hungary, 7900
    • Research Site
  • Zalaegerszeg, Hungary, 8900
    • Research Site
• Israel
  • Ashkelon, Israel, 78278
    • Research Site
  • Jerusalem, Israel, 91120
    • Research Site
  • Tel Aviv, Israel, 64239
    • Research Site
  • Tel Hashomer, Israel, 52621
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  • Zerifin, Israel, 70300
    • Research Site
• Italy
  • Ancona, Italy, 60126
    • Research Site
  • Firenze, Italy, 50139
    • Research Site
  • Genova, Italy, 16132
    • Research Site
  • Lecco, Italy, 23900
    • Research Site
  • Lucca, Italy, 55100
    • Research Site
  • Milano, Italy, 20122
    • Research Site
  • Pavia, Italy, 27100
    • Research Site
  • Pisa, Italy, 56126
    • Research Site
  • Pordenone, Italy, 33170
    • Research Site
  • Verona, Italy, 37126
    • Research Site
• Latvia
  • Riga, Latvia, 1001
    • Research Site
• Lithuania
  • Alytus, Lithuania, 63351
    • Research Site
  • Kaunas, Lithuania, 50009
    • Research Site
  • Kaunas, Lithuania, 50169
    • Research Site
  • Ukmerge, Lithuania, 20184
    • Research Site
• Netherlands
  • Rotterdam, Netherlands, 3079 DZ
    • Research Site
  • Venlo, Netherlands, 5912 BL
    • Research Site
• New Zealand
  • Hamilton, New Zealand, 3240
    • Research Site
• Poland
  • Gdansk, Poland, 80-952
    • Research Site
  • Golub-Dobrzyn, Poland, 87-400
    • Research Site
  • Katowice, Poland, 40-027
    • Research Site
  • Krakow, Poland, 31-501
    • Research Site
  • Lodz, Poland, 90-153
    • Research Site
  • Poznan, Poland, 60-355
    • Research Site
  • Poznan, Poland, 61-696
    • Research Site
  • Sieradz, Poland, 98-200
    • Research Site
  • Wadowice, Poland, 34-100
    • Research Site
  • Warszawa, Poland, 02-097
    • Research Site
  • Warszawa, Poland, 02-507
    • Research Site
  • Zabrze, Poland, 41-800
    • Research Site
  • Zamosc, Poland, 87-100
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  • Zyrardow, Poland, 96-300
    • Research Site
• Portugal
  • Almada, Portugal, 2800-455
    • Research Site
  • Aveiro, Portugal, 3800-266
    • Research Site
  • Forte da Casa, Portugal, 2625-437
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  • Guimarães, Portugal, 4810-273
    • Research Site
  • Lisboa, Portugal, 1750-130
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  • Santo Tirso, Portugal, 4780-383
    • Research Site
  • Setubal, Portugal, 2900-655
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  • Vila Franca de Xira, Portugal, 2600-076
    • Research Site
• Russian Federation
  • Mitishi, Russian Federation, 141009
    • Research Site
  • Moscow, Russian Federation, 129327
    • Research Site
  • Petrozavodsk, Russian Federation, 185019
    • Research Site
  • Saint Petersburg, Russian Federation, 191104
    • Research Site
  • Saint Petersburg, Russian Federation, 196247
    • Research Site
  • Saint Petersburg, Russian Federation, 197110
    • Research Site
  • Saint Petersburg, Russian Federation, 198510
    • Research Site
  • Saint-Petersburg, Russian Federation, 193318
    • Research Site
  • Saint-Petersburg, Russian Federation, 195067
    • Research Site
  • Saint-Petersburg, Russian Federation, 195257
    • Research Site
  • Yaroslavl, Russian Federation, 150062
    • Research Site
• Spain
  • Madrid, Spain, 28041
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Andalucía
    • Cordoba, Andalucía, Spain, 14004
      • Research Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Research Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08025
      • Research Site
    • Barcelona, Cataluña, Spain, 08036
      • Research Site
    • Barcelona, Cataluña, Spain, 08003
      • Research Site
    • Barcelona, Cataluña, Spain, 08035
      • Research Site
    • Lleida, Cataluña, Spain, 25198
      • Research Site
  • Comunidad Valenciana
    • Torrevieja, Comunidad Valenciana, Spain, 03186
      • Research Site
    • Valencia, Comunidad Valenciana, Spain, 46017
      • Research Site
  • Extremadura
    • Badajoz, Extremadura, Spain, 06080
      • Research Site
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Research Site
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Research Site
• Sweden
  • Karlstad, Sweden, 651 85
    • Research Site
  • Stockholm, Sweden, 118 67
    • Research Site
  • Stockholm, Sweden, 141 86
    • Research Site
  • Trollhättan, Sweden, 467 85
    • Research Site
  • Uppsala, Sweden, 751 85
    • Research Site
• Switzerland
  • Aarau, Switzerland, 5001
    • Research Site
  • Bern, Switzerland, 3010
    • Research Site
  • Geneva 14, Switzerland, 1211
    • Research Site
  • Lausanne, Switzerland, 1011
    • Research Site
  • Lausanne, Switzerland, 1003
    • Research Site
  • Locarno, Switzerland, 6600
    • Research Site
  • Zurich, Switzerland, 8091
    • Research Site
• Turkey
  • Ankara, Turkey, 06230
    • Research Site
  • Ankara, Turkey, 06810
    • Research Site
  • Istanbul, Turkey, 34371
    • Research Site
  • Istanbul, Turkey, 34890
    • Research Site
  • Izmir, Turkey, 35100
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Research Site
  • California
    • Alhambra, California, United States, 91801
      • Research Site
    • Azusa, California, United States, 91702
      • Research Site
    • Bakersfield, California, United States, 93308
      • Research Site
    • Cudahy, California, United States, 90201
      • Research Site
    • Granada Hills, California, United States, 91344
      • Research Site
    • Los Angeles, California, United States, 90022
      • Research Site
    • Los Angeles, California, United States, 90048
      • Research Site
    • Northridge, California, United States, 91324
      • Research Site
    • Riverside, California, United States, 92501
      • Research Site
    • Simi Valley, California, United States, 93065
      • Research Site
    • Vacaville, California, United States, 95687
      • Research Site
    • Whittier, California, United States, 90603
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
    • Westminster, Colorado, United States, 80031
      • Research Site
  • Connecticut
    • Stamford, Connecticut, United States, 06902
      • Research Site
  • Florida
    • Miami, Florida, United States, 33150
      • Research Site
    • Ocala, Florida, United States, 34471
      • Research Site
    • Pembroke Pines, Florida, United States, 33028
      • Research Site
    • Tampa, Florida, United States, 33614
      • Research Site
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Research Site
    • Dublin, Georgia, United States, 31021
      • Research Site
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Research Site
  • Illinois
    • Highland Park, Illinois, United States, 60035
      • Research Site
  • Indiana
    • Merrillville, Indiana, United States, 46410
      • Research Site
    • Michigan City, Indiana, United States, 46360
      • Research Site
  • Kansas
    • Wichita, Kansas, United States, 67214-2998
      • Research Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Research Site
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48236
      • Research Site
    • Pontiac, Michigan, United States, 48341
      • Research Site
  • Mississippi
    • Brookhaven, Mississippi, United States, 39601
      • Research Site
    • Columbus, Mississippi, United States, 39705
      • Research Site
    • Gulfport, Mississippi, United States, 39501
      • Research Site
    • Tupelo, Mississippi, United States, 38801
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Research Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Research Site
    • Reno, Nevada, United States, 89511
      • Research Site
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Research Site
    • Voorhees, New Jersey, United States, 08043
      • Research Site
  • New York
    • Brooklyn, New York, United States, 11235
      • Research Site
    • College Point, New York, United States, 11356
      • Research Site
    • Great Neck, New York, United States, 11021
      • Research Site
    • Mineola, New York, United States, 11501
      • Research Site
    • Rosedale, New York, United States, 11422
      • Research Site
    • The Bronx, New York, United States, 10461
      • Research Site
    • Yonkers, New York, United States, 10704
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27704
      • Research Site
    • New Bern, North Carolina, United States, 28562
      • Research Site
    • Wilmington, North Carolina, United States, 28401
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Research Site
    • Columbus, Ohio, United States, 43215
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Research Site
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19106
      • Research Site
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Research Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37408
      • Research Site
    • Knoxville, Tennessee, United States, 37923
      • Research Site
  • Texas
    • Arlington, Texas, United States, 76015
      • Research Site
    • Edinburg, Texas, United States, 78539
      • Research Site
    • Houston, Texas, United States, 77030
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22033
      • Research Site
    • Hampton, Virginia, United States, 23666
      • Research Site
    • Mechanicsville, Virginia, United States, 23116
      • Research Site
  • West Virginia
    • Bluefield, West Virginia, United States, 24701
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 110 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject has provided informed consent prior to initiation of any study-specific activities/procedures
• Subject has completed treatment in Study 20120231 (also known as KAI-4169-008) or Study 20120360, or has participated in Study 20120334 (also known as KAI-4169-005-01)
• Female subjects who are: post-menopausal (post-menopausal is defined as no menses for the previous 1 year and over the age of 50 years), surgically sterilized, have a medical condition that prevents pregnancy, remain abstinent, or are willing to use an acceptable method of effective contraception during the study and for 3 months after the last dose. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 2 weeks prior to the first dose of AMG 416 in the current study
• Subject must be receiving hemodialysis 3 or 4 times weekly for at least 3 months

Exclusion Criteria:

• Currently receiving treatment in another investigational device or drug study (other than in one of the designated parent studies)
• Subject has known sensitivity to any of the products or components to be administered during dosing
• Subject has been prescribed cinacalcet by the primary nephrologist between the conclusion of the parent study and the start of dosing with AMG 416 in the current study
• Subject is receiving dialysis prescription dialysate calcium concentration < 2.25 mEq/L
• Subject is pregnant or nursing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Etelcalcetide; Participants received etelcalcetide three times a week (TIW) by bolus injection at the end of hemodialysis. The minimum etelcalcetide dose in this study was 2.5 mg and the maximum dose was 15 mg. Etelcalcetide dose was titrated to maintain parathyroid hormone levels within 2x to 9x the upper limit of normal based on the reference range of the assay used at the individual study center.

Drug: Etelcalcetide; Etelcalcetide was supplied as a sterile, preservative-free, ready-to-administer aqueous solution.; Other Names: KAI-4169; AMG 416; Parasabiv

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	A serious adverse event is an AE that met at least 1 of the following criteria: fatal; life threatening; required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. The relationship of each AE to study treatment was assessed by the investigator. The following AE grading scale was used: Mild: Transient or mild discomfort; no limitation in activity; no medical intervention/therapy required Moderate: Mild to moderate limitation in activity-some assistance may be needed; no or minimal medical intervention/therapy required Severe: Marked limitation in activity, some assistance usually required; medical intervention/therapy required, hospitalization possible Life-threatening: Extreme limitation in activity, significant assistance required, significant medical intervention/therapy required, hospitalization probable.	From the date of first dose of etelcalcetide (in the current study) and up to 30 days after the last dose; median duration of treatment was 563 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Parathyroid Hormone Levels Between Two to Nine-times the Upper Limit of Normal	The percentage of participants who maintained plasma parathyroid hormone (PTH) levels within the Kidney Disease Improving Global Outcomes (KDIGO) recommended range of not less than 2x the upper limit of normal (ULN) and not greater than 9x the ULN at months 6, 12, and 18, with the ULN based on the reference range of the assay used at the individual clinical site.	Months 6, 12, and 18
Percentage of Participants With Serum Phosphorus ≤ the ULN	Percentage of participants with serum phosphorus less than or equal to the upper limit of normal for the assay used.	Months 6, 12, and 18
Percentage of Participants With Serum Corrected Calcium < 7.5 mg/dL	The percentage of participants with serum corrected calcium (cCa) reported for cumulative time intervals from day 1 through months 6, 12, and 18, using the participant's lowest recorded corrected calcium value during the time interval. If serum albumin was less than 4.0 g/dL, serum calcium was corrected according to the following formula: cCa (mg/dL) = total calcium (mg/dL) + (4 - albumin [g/dL])*0.8. If serum albumin was > 4.0 g/dL no correction was made.	From day 1 to months 6, 12, and 18
Number of Participants With Shifts From Baseline Grade 0 or 1 to Postbaseline Grade 3 or 4 for Laboratory Parameters	The Common Terminology Criteria for Adverse Events (CTCAE) grades for laboratory parameter values were defined based on the upper/lower limit of normal from the local laboratories contracted by the study centers.	Baseline to end of treatment; median duration of treatment was 563 days.
Number of Participants Who Developed Positive Binding Anti-Etelcalcetide Antibodies	The number of participants who were binding antibody positive post-baseline with a negative or no result at baseline (where baseline for participants previously treated with etelcalcetide is Day 1 of the first study in which they were exposed to etelcalcetide and for participants previously treated with cinacalcet is the ending time point for study 20120360).	Baseline and every 6 months (up to 24 months)

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2014
• Primary Completion (Actual): November 4, 2016
• Study Completion (Actual): June 26, 2017

Study Registration Dates

• First Submitted: March 3, 2014
• First Submitted That Met QC Criteria: March 31, 2014
• First Posted (Estimate): April 2, 2014

Study Record Updates

• Last Update Posted (Actual): November 17, 2017
• Last Update Submitted That Met QC Criteria: October 18, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Secondary Hyperparathyroidism (SHPT), chrominc kidney disease (CKD), hemodialysis
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Parathyroid Diseases; Neoplastic Processes; Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism; Neoplasm Metastasis; Hyperparathyroidism, Secondary
• Other Study ID Numbers: 20130213; 2013-004136-30 (EudraCT Number); KAI-4169 (Other Identifier: KAI Pharmaceuticals (wholly owned subsidiary of Amgen Inc.))

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No