Clinical trial NCT01785849: Efficacy and Safety of Etelcalcetide (AMG 416) in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease on Hemodialysis
Official title: A Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Assess the Efficacy and Safety of AMG 416 in the Treatment of Secondary Hyperparathyroidism in Subjects With Chronic Kidney Disease on Hemodialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperparathyroidism, Secondary
Keywords: Secondary Hyperparathyroidism (SHPT), chronic kidney disease (CKD), hemodialysis, parathyroid hormone (PTH), hypocalcemia, bone and mineral metabolism
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2013-02-07
Enrollment: 508
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to assess the efficacy and safety of etelcalcetide compared with placebo in the treatment of SHPT in patients with chronic kidney disease (CKD) receiving hemodialysis.


Eligibility criteria: Inclusion Criteria:

* Subject understands the study procedures and agrees to participate in the study by giving written informed consent.
* Subject is 18 years of age or older.
* Subject must be receiving hemodialysis 3 times weekly for at least 3 months
* Subject agrees to not participate in another study of an investigational agent during the study.
* Other Inclusion Criteria may apply

Exclusion Criteria:

* Currently receiving treatment in another investigational device or drug study, or ended treatment on another investigational device or drug study(s) within 8 weeks prior to screening.
* Other investigational procedures while participating in this study are excluded.
* Anticipated or scheduled parathyroidectomy during the study period.
* Subject has received a parathyroidectomy within 3 months prior to dosing.
* Anticipated or scheduled kidney transplant during the study period.
* Subject has known sensitivity to any of the products or components to be administered during dosing.
* Subject has participated in a prior clinical trial of AMG 416 (also referred to as KAI-4169).
* Subject has received cinacalcet within the 4 weeks prior to screening labs (treatment with cinacalcet is prohibited during the study).
* Subject has an unstable medical condition based on medical history, physical examination, and routine laboratory tests, or is otherwise unstable in the judgment of the Investigator.
* Other Exclusion Criteria may apply

Primary outcomes:
measure: Percentage of Participants With a > 30% Decrease From Baseline in Mean PTH During the Efficacy Assessment Phase
timeFrame: Baseline and the efficacy assessment phase (EAP; defined as Weeks 20 to 27, inclusive).
Secondary outcomes:
measure: Percentage of Participants With Mean Predialysis Parathyroid Hormone ≤ 300 pg/mL During the Efficacy Assessment Phase
timeFrame: Baseline and the efficacy assessment phase (Week 20 to Week 27)
measure: Percent Change From Baseline in Predialysis PTH During the Efficacy Assessment Phase
timeFrame: Baseline and the Efficacy Assessment Phase (Week 20 to Week 27)
measure: Percent Change From Baseline in Predialysis Corrected Calcium During the Efficacy Assessment Phase
timeFrame: Baseline and the efficacy assessment phase (Week 20 to Week 27)
measure: Percent Change From Baseline in Predialysis Corrected Calcium Phosphorus Product During the Efficacy Assessment Phase
timeFrame: Baseline and the efficacy assessment phase (Week 20 to Week 27)
measure: Percent Change From Baseline in Predialysis Phosphorus During the Efficacy Assessment Phase
timeFrame: Baseline and the efficacy assessment phase (Week 20 to Week 27)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Pine Bluff
country: United States
facility: Research Site
state: Arkansas
city: Azusa
country: United States
facility: Research Site
state: California
city: Covina
country: United States
facility: Research Site
state: California
city: Lakewood
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Lynwood
country: United States
facility: Research Site
state: California
city: Northridge
country: United States
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state: California
city: Ontario
country: United States
facility: Research Site
state: California
city: Panorama City
country: United States
facility: Research Site
state: California
city: Sacramento
country: United States
facility: Research Site
state: California
city: Whittier
country: United States
facility: Research Site
state: California
city: Pembroke Pines
country: United States
facility: Research Site
state: Florida
city: Meridian
country: United States
facility: Research Site
state: Idaho
city: Evanston
country: United States
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state: Illinois
city: Springfield
country: United States
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state: Massachusetts
city: Detroit
country: United States
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state: Michigan
city: Kalamazoo
country: United States
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state: Michigan
city: Pontiac
country: United States
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state: Michigan
city: Southgate
country: United States
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state: Michigan
city: Tupelo
country: United States
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state: Mississippi
city: Kansas City
country: United States
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state: Missouri
city: Reno
country: United States
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state: Nevada
city: Amherst
country: United States
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state: New York
city: Bronx
country: United States
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state: New York
city: Brooklyn
country: United States
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state: New York
city: Rosedale
country: United States
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state: New York
city: Yonkers
country: United States
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state: New York
city: Chapel Hill
country: United States
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state: North Carolina
city: Durham
country: United States
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state: North Carolina
city: Allentown
country: United States
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state: Pennsylvania
city: Philadelphia
country: United States
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state: Pennsylvania
city: Philadelphia
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state: Pennsylvania
city: Orangeburg
country: United States
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state: South Carolina
city: Sumter
country: United States
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state: South Carolina
city: Columbia
country: United States
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state: Tennessee
city: Nashville
country: United States
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state: Tennessee
city: Austin
country: United States
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state: Texas
city: Fort Worth
country: United States
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state: Texas
city: Fort Worth
country: United States
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state: Texas
city: Grand Prairie
country: United States
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state: Texas
city: Houston
country: United States
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state: Texas
city: Mansfield
country: United States
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state: Texas
city: San Antonio
country: United States
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state: Texas
city: San Antonio
country: United States
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state: Texas
city: San Antonio
country: United States
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state: Texas
city: Tyler
country: United States
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state: Texas
city: Fairfax
country: United States
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state: Virginia
city: Mechanicsville
country: United States
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state: Virginia
city: Norfolk
country: United States
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state: Virginia
city: Bluefield
country: United States
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state: West Virginia
city: Liverpool
country: Australia
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state: New South Wales
city: St Leonards
country: Australia
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state: New South Wales
city: Parkville
country: Australia
facility: Research Site
state: Victoria
city: Prahan
country: Australia
facility: Research Site
state: Victoria
city: Graz
country: Austria
facility: Research Site
city: Linz
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Aalst
country: Belgium
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city: Baudour
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
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city: Liège
country: Belgium
facility: Research Site
city: Brampton
country: Canada
facility: Research Site
state: Ontario
city: Greenfield Park
country: Canada
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state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Hradec Kralove
country: Czechia
facility: Research Site
city: Praha 4 - Nusle
country: Czechia
facility: Research Site
city: Praha 6
country: Czechia
facility: Research Site
city: Slavkov u Brna
country: Czechia
facility: Research Site
city: Trinec
country: Czechia
facility: Research Site
city: Nantes Cedex 01
country: France
facility: Research Site
city: Poitiers
country: France
facility: Research Site
city: Reims Cedex
country: France
facility: Research Site
city: Saint-Ouen
country: France
facility: Research Site
city: Salouel Cedex 1
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Kiel
country: Germany
facility: Research Site
city: Villingen-Schwenningen
country: Germany
facility: Research Site
city: Baja
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Gyor
country: Hungary
facility: Research Site
city: Kaposvar
country: Hungary
facility: Research Site
city: Pecs
country: Hungary
facility: Research Site
city: Ashkelon
country: Israel
facility: Research Site
city: Nahariya
country: Israel
facility: Research Site
city: Tel Aviv
country: Israel
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Pavia
country: Italy
facility: Research Site
city: San Fermo Della Battaglia (CO)
country: Italy
facility: Research Site
city: Verona
country: Italy
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Zamosc
country: Poland
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Santander
country: Spain
facility: Research Site
state: Cantabria
city: Barcelona
country: Spain
facility: Research Site
state: Cataluña
city: Barcelona
country: Spain
facility: Research Site
state: Cataluña
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Coventry
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Salford
country: United Kingdom
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Block GA, Bushinsky DA, Cunningham J, Drueke TB, Ketteler M, Kewalramani R, Martin KJ, Mix TC, Moe SM, Patel UD, Silver J, Spiegel DM, Sterling L, Walsh L, Chertow GM. Effect of Etelcalcetide vs Placebo on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: Two Randomized Clinical Trials. JAMA. 2017 Jan 10;317(2):146-155. doi: 10.1001/jama.2016.19456.
citation: Kroenke MA, Weeraratne DK, Deng H, Sloey B, Subramanian R, Wu B, Serenko M, Hock MB. Clinical immunogenicity of the d-amino acid peptide therapeutic etelcalcetide: Method development challenges and anti-drug antibody clinical impact assessments. J Immunol Methods. 2017 Jun;445:37-44. doi: 10.1016/j.jim.2017.03.005. Epub 2017 Mar 6.
citation: 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.
citation: 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.
citation: Chen P, Narayanan A, Wu B, Gisleskog PO, Gibbs JP, Chow AT, Melhem M. Population Pharmacokinetic and Pharmacodynamic Modeling of Etelcalcetide in Patients with Chronic Kidney Disease and Secondary Hyperparathyroidism Receiving Hemodialysis. Clin Pharmacokinet. 2018 Jan;57(1):71-85. doi: 10.1007/s40262-017-0550-4.
citation: 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.
citation: Cunningham J, Block GA, Chertow GM, Cooper K, Evenepoel P, Iles J, Sun Y, Urena-Torres P, Bushinsky DA. Etelcalcetide Is Effective at All Levels of Severity of Secondary Hyperparathyroidism in Hemodialysis Patients. Kidney Int Rep. 2019 Apr 16;4(7):987-994. doi: 10.1016/j.ekir.2019.04.010. eCollection 2019 Jul.
citation: 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.
citation: Hain D, Tomlin H, Gibson C. Administration of Etelcalcetide for the Treatment of Secondary Hyperparathyroidism in Patients with CKD-MBD on Hemodialysis: A Nephrology Nursing Perspective. Nephrol Nurs J. 2019 May-Jun;46(3):315-290.