Head-to-Head Study of Etelcalcetide (AMG 416) and Cinacalcet

A Multicenter, Multiple-dose, Two-arm, Active-controlled, Double-blind, Double-dummy Study to Compare the Therapeutic Efficacy and Safety of Oral Doses of Cinacalcet HCl With Intravenous Doses of AMG 416 in Hemodialysis Subjects With Secondary Hyperparathyroidism

The purpose of this study is to demonstrate that treatment with etelcalcetide (AMG 416) is not inferior to treatment with cinacalcet for lowering serum parathyroid hormone (PTH) levels by > 30% from baseline among patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT) who require management with hemodialysis.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; Secondary Hyperparathyroidism
• Intervention / Treatment: Drug: Cinacalcet; Drug: Intravenous Placebo; Drug: Etelcalcetide; Drug: Oral Placebo

• Study Type: Interventional
• Enrollment (Actual): 683
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Feldkirch, Austria, 6807
    • Research Site
  • Linz, Austria, 4010
    • Research Site
  • Wien, Austria, 1220
    • Research Site
• Belgium
  • Genk, Belgium, 3600
    • Research Site
  • Hasselt, Belgium, 3500
    • Research Site
  • Kortrijk, Belgium, 8500
    • Research Site
  • Roeselare, Belgium, 8800
    • Research Site
• 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
• Czechia
  • Novy Jicin, Czechia, 741 01
    • Research Site
  • Praha 4 - Nusle, Czechia, 140 00
    • Research Site
  • Praha 6, Czechia, 169 00
    • Research Site
  • Slavkov u Brna, Czechia, 684 01
    • Research Site
  • Trinec, Czechia, 739 61
    • Research Site
  • Usti nad Orlici, Czechia, 562 18
    • Research Site
• Denmark
  • Aalborg, Denmark, 9000
    • Research Site
  • Fredericia, Denmark, 7000
    • Research Site
  • Kobenhavn, Denmark, 2100
    • Research Site
  • Odense, Denmark, 5000
    • Research Site
  • Roskilde, Denmark, 4000
    • Research Site
• Estonia
  • Tallinn, Estonia, 10617
    • Research Site
  • Tallinn, Estonia, 13419
    • Research Site
  • Tartu, Estonia, 51014
    • Research Site
• France
  • Boulogne sur Mer, France, 62200
    • Research Site
  • Lille Cedex, France, 59800
    • Research Site
  • Nouilly, France, 57645
    • Research Site
  • Paris, France, 75014
    • Research Site
  • Paris, France, 75011
    • Research Site
  • Saint Ouen, France, 93400
    • Research Site
  • Saint Priest en Jarez, France, 42270
    • Research Site
  • Saint-Ouen, France, 93400
    • Research Site
  • Sainte Foy les Lyon, France, 66046
    • Research Site
• Germany
  • Aachen, Germany, 52074
    • Research Site
  • Coburg, Germany, 96450
    • Research Site
  • Hamburg, Germany, 22297
    • Research Site
  • Hannover, Germany, 30625
    • Research Site
  • Magdeburg, Germany, 39120
    • Research Site
  • Mettmann, Germany, 40822
    • Research Site
  • Minden, Germany, 32429
    • Research Site
  • München, Germany, 81675
    • Research Site
  • Wiesbaden, Germany, 65191
    • Research Site
  • Zwickau, Germany, 08060
    • Research Site
• Greece
  • Alexandroupoli, Greece, 68100
    • Research Site
  • Athens, Greece, 11528
    • Research Site
  • Ioannina, Greece, 45500
    • Research Site
  • Larissa, Greece, 41110
    • Research Site
  • Nikaia, Piraeus, Greece, 18454
    • Research Site
  • Patra, Greece, 26500
    • Research Site
  • Thessaloniki, Greece, 54636
    • Research Site
• Hungary
  • Budapest, Hungary, 1115
    • Research Site
  • Gyor, Hungary, 9023
    • Research Site
  • Kaposvar, Hungary, 7400
    • Research Site
  • Kistarcsa, Hungary, 2143
    • Research Site
  • 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
• Italy
  • Cagliari, Italy, 09134
    • 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
  • San Giovanni Rotondo FG, Italy, 71013
    • Research Site
• Latvia
  • Riga, Latvia, 1001
    • Research Site
  • Riga, Latvia, 1038
    • Research Site
  • Valmiera, Latvia, 4201
    • Research Site
• Lithuania
  • Alytus, Lithuania, 63351
    • Research Site
  • Kaunas, Lithuania, 50009
    • Research Site
  • Kaunas, Lithuania, 50169
    • Research Site
  • Kedainiai, Lithuania, 57164
    • Research Site
  • Klaipeda, Lithuania, LT-93220
    • Research Site
  • Siauliai, Lithuania, 76299
    • Research Site
  • Ukmerge, Lithuania, 20184
    • Research Site
• New Zealand
  • Hamilton, New Zealand, 3240
    • Research Site
  • Papatoetoe, Auckland, New Zealand, 2025
    • Research Site
  • Takapuna, Auckland City, New Zealand, 0622
    • Research Site
• Poland
  • Gdansk, Poland, 80-104
    • Research Site
  • Katowice, Poland, 40-027
    • 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
  • Warsawa, Poland, 01-211
    • Research Site
  • Warszawa, Poland, 02-507
    • Research Site
  • Zabrze, Poland, 41-800
    • Research Site
  • Zyrardow, Poland, 96-300
    • Research Site
• Portugal
  • Almada, Portugal, 2800-455
    • Research Site
  • Aveiro, Portugal, 3800-266
    • Research Site
  • Estoril, Portugal, 2765-294
    • Research Site
  • Forte Da Casa, Portugal, 2625-437
    • Research Site
  • Guimarães, Portugal, 4810-273
    • Research Site
  • Lisboa, Portugal, 1750-130
    • Research Site
  • Santo Tirso, Portugal, 4780-383
    • Research Site
  • Setubal, Portugal, 2900-655
    • Research Site
  • Vila Franca de Xira, Portugal, 2600-076
    • Research Site
• Russian Federation
  • Mitishi, Russian Federation, 141009
    • Research Site
  • Moscow, Russian Federation, 129327
    • Research Site
  • Moscow, Russian Federation, 123182
    • Research Site
  • Petrozavodsk, Russian Federation, 185019
    • Research Site
  • Saint Petersburg, Russian Federation, 191104
    • 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
  • Yaroslavl, Russian Federation, 150062
    • Research Site
• Spain
  • Madrid, Spain, 28040
    • Research Site
  • Madrid, Spain, 28007
    • Research Site
  • Andalucía
    • Cordoba, Andalucía, Spain, 14004
      • Research Site
    • Puerto Real, Andalucía, Spain, 11510
      • Research Site
  • Cataluña
    • Badalona, Cataluña, Spain, 08916
      • 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
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Research Site
  • País Vasco
    • Galdakao, País Vasco, Spain, 48960
      • Research Site
• Sweden
  • Malmö, Sweden, 205 02
    • Research Site
  • Stockholm, Sweden, 118 67
    • Research Site
  • Trollhättan, Sweden, 467 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
  • Ankara, Turkey, 06500
    • Research Site
  • Istanbul, Turkey, 34371
    • Research Site
  • Istanbul, Turkey, 34890
    • Research Site
  • Izmir, Turkey, 35100
    • Research Site
  • Izmir, Turkey, 35360
    • Research Site
  • Izmir, Turkey, 35340
    • Research Site
• United States
  • California
    • Azusa, California, United States, 91702
      • Research Site
    • Bakersfield, California, United States, 93309
      • Research Site
    • Bakersfield, California, United States, 93306
      • Research Site
    • Chula Vista, California, United States, 91910
      • Research Site
    • Covina, California, United States, 91723
      • Research Site
    • Granada Hills, California, United States, 91344
      • Research Site
    • La Mesa, California, United States, 91942
      • Research Site
    • La Puente, California, United States, 91744
      • Research Site
    • Los Angeles, California, United States, 90022
      • Research Site
    • San Diego, California, United States, 92123
      • Research Site
    • San Gabriel, California, United States, 91776
      • Research Site
    • Whittier, California, United States, 90603
      • Research Site
  • Colorado
    • Arvada, Colorado, United States, 80002
      • Research Site
    • Aurora, Colorado, United States, 80045
      • Research Site
    • Longmont, Colorado, United States, 80501
      • Research Site
    • Westminster, Colorado, United States, 80031
      • Research Site
  • Connecticut
    • Orange, Connecticut, United States, 06477
      • Research Site
  • Florida
    • Pembroke Pines, Florida, United States, 33028
      • Research Site
    • Pinecrest, Florida, United States, 33156
      • Research Site
    • Tampa, Florida, United States, 33614
      • Research Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Research Site
    • Lafayette, Louisiana, United States, 70501
      • Research Site
  • Michigan
    • Southgate, Michigan, United States, 48195
      • Research Site
  • Mississippi
    • Columbus, Mississippi, United States, 39705
      • Research Site
    • Gulfport, Mississippi, United States, 39501
      • Research Site
  • New Jersey
    • Sewell, New Jersey, United States, 08080
      • Research Site
  • New York
    • Bronx, New York, United States, 10461
      • Research Site
    • Great Neck, New York, United States, 11021
      • Research Site
    • Mineola, New York, United States, 11501
      • Research Site
    • Ridgewood, New York, United States, 11385
      • Research Site
    • Rosedale, New York, United States, 11422
      • Research Site
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45206
      • Research Site
    • Columbus, Ohio, United States, 43215
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19106
      • Research Site
  • Texas
    • 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
    • Portsmouth, Virginia, United States, 23704
      • Research Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53713
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Eligible subjects must be receiving adequate thrice weekly maintenance hemodialysis with a dialysate calcium concentration ≥ 2.5 mEq/L for at least 3 months prior to screening laboratory assessments
• Subjects must have SHPT as defined by one central laboratory screening predialysis serum PTH value > 500 pg/mL, measured on separate days within 2 weeks prior to randomization
• Subjects must have one serum cCa value ≥ 8.3 mg/dL obtained before dialysis within 2 weeks of the date of randomization
• Subjects receiving calcium supplements must have no more than a maximum dose change of 50% within 2 weeks before screening laboratory assessments are obtained, and the dose must remain unchanged through randomization

Exclusion Criteria:

• Eligible subjects cannot have received cinacalcet during the 3 months preceding the first screening laboratory assessment
• Other criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cinacalcet; Participants were randomized to receive oral cinacalcet once daily and placebo intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 30 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining corrected calcium (cCa) ≥ 8.3 mg/dL.	Drug: Cinacalcet; Cinacalcet was administered orally once a day. The starting dose was 30 mg daily, titrated up to 180 mg daily based on serum PTH and corrected calcium levels.; Other Names: Sensipar®, Mimpara®; Drug: Intravenous Placebo; Administered intravenously (IV) three times per week.
Experimental: Etelcalcetide; Participants were randomized to receive etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW, and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.	Drug: Etelcalcetide; Administered intravenously three times per week. The starting dose was 5 mg, titrated up to 15 mg based on serum PTH and corrected calcium levels.; Other Names: AMG 416; Drug: Oral Placebo; Administered orally once a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With > 30% Reduction From Baseline in Mean Parathyroid Hormone During the Efficacy Assessment Phase - Non-inferiority Analysis	Baseline and the efficacy assessment phase (EAP; defined as Weeks 20 to 27, inclusive).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With > 50% Reduction From Baseline in Mean PTH During the Efficacy Assessment Phase		Baseline and the efficacy assessment phase (Weeks 20 to 27, inclusive).
Percentage of Participants With > 30% Reduction From Baseline in Mean PTH During the Efficacy Assessment Phase		Baseline and the efficacy assessment phase (Week 20 to Week 27)
Mean Number of Days of Vomiting or Nausea Per Week in the First 8 Weeks	Participants completed the Nausea/Vomiting Symptom Assessment (NVSA) questionnaire daily. This questionnaire asked participants to indicate the severity of nausea on a scale from 0 (no nausea) to 10 (as severe as can be imagined) and if they had vomited in the past 24 hours. A day of vomiting or nausea was defined as those where the severity of nausea score was > 0 or where the episodes of vomiting score was > 0.	First 8 weeks
Percent Change From Baseline in Mean Corrected Calcium During the Efficacy Assessment Phase		Baseline and the efficacy assessment phase (weeks 20 - 27)
Percentage of Participants With Mean Predialysis Serum Phosphorus ≤ 4.5 mg/dL During the Efficacy Assessment Phase		Efficacy assessment phase (weeks 20 - 27)
Mean Severity of Nausea in the First 8 Weeks	Severity of nausea was assessed using the Nausea and Vomiting Symptom Assessment questionnaire which asked participants to rate the severity of nausea on a scale from 0 (no nausea) to 10 (as severe as can be imagined). For each participant, the mean severity of nausea was calculated by averaging all available daily severities (including zeroes) reported in the first 8 weeks.	First 8 weeks
Mean Number of Episodes of Vomiting Per Week in the First 8 Weeks	The number of vomiting episodes was assessed using the Nausea and Vomiting Symptom Assessment questionnaire which asks participants on a daily basis how many times they vomited in the past 24 hours. The number of episodes in a week is the sum of all reported daily episodes in the week. For participants providing less than 7 days of responses to NVSA questions in any given week, data from that week did not contribute to the analysis.	First 8 weeks

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Stollenwerk B, Iannazzo S, Akehurst R, Adena M, Briggs A, Dehmel B, Parfrey P, Belozeroff V. A Decision-Analytic Model to Assess the Cost-Effectiveness of Etelcalcetide vs. Cinacalcet. Pharmacoeconomics. 2018 May;36(5):603-612. doi: 10.1007/s40273-017-0605-2.
• Stollenwerk B, Iannazzo S, Cooper K, Belozeroff V. Exploring the potential value of improved care for secondary hyperparathyroidism with a novel calcimimetic therapy. J Med Econ. 2017 Oct;20(10):1110-1115. doi: 10.1080/13696998.2017.1360309. Epub 2017 Aug 14.
• Block GA, Chertow GM, Sullivan JT, Deng H, Mather O, Tomlin H, Serenko M. An integrated analysis of safety and tolerability of etelcalcetide in patients receiving hemodialysis with secondary hyperparathyroidism. PLoS One. 2019 Mar 15;14(3):e0213774. doi: 10.1371/journal.pone.0213774. eCollection 2019.
• Wolf M, Block GA, Chertow GM, Cooper K, Fouqueray B, Moe SM, Sun Y, Tomlin H, Vervloet M, Oberbauer R. Effects of etelcalcetide on fibroblast growth factor 23 in patients with secondary hyperparathyroidism receiving hemodialysis. Clin Kidney J. 2019 Apr 26;13(1):75-84. doi: 10.1093/ckj/sfz034. eCollection 2020 Feb.
• Block GA, Bushinsky DA, Cheng S, Cunningham J, Dehmel B, Drueke TB, Ketteler M, Kewalramani R, Martin KJ, Moe SM, Patel UD, Silver J, Sun Y, Wang H, Chertow GM. Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: A Randomized Clinical Trial. JAMA. 2017 Jan 10;317(2):156-164. doi: 10.1001/jama.2016.19468.
• Wu B, Melhem M, Subramanian R, Chen P, Jaramilla Sloey B, Fouqueray B, Hock MB, Skiles GL, Chow AT, Lee E. Clinical Pharmacokinetics and Pharmacodynamics of Etelcalcetide, a Novel Calcimimetic for Treatment of Secondary Hyperparathyroidism in Patients With Chronic Kidney Disease on Hemodialysis. J Clin Pharmacol. 2018 Jun;58(6):717-726. doi: 10.1002/jcph.1090. Epub 2018 Mar 13.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2013
• Primary Completion (Actual): November 12, 2014
• Study Completion (Actual): January 8, 2015

Study Registration Dates

• First Submitted: July 8, 2013
• First Submitted That Met QC Criteria: July 8, 2013
• First Posted (Estimate): July 11, 2013

Study Record Updates

• Last Update Posted (Actual): July 18, 2019
• Last Update Submitted That Met QC Criteria: July 8, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Secondary Hyperparathyroidism, renal, kidney, kidneys, dialysis, hemodialysis, chronic kidney disease, CKD, SHPT
• 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; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Calcium-Regulating Hormones and Agents; Calcimimetic Agents; Cinacalcet
• Other Study ID Numbers: 20120360; 2013-000192-33 (EudraCT Number)