Efficacy and Safety of Etelcalcetide (AMG 416) in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease on Hemodialysis

Hyperparathyroidism, Secondary Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01785849
• Other study ID #: 20120229
• Secondary ID: KAI-4169-0062012
• Status: Completed
• Phase: Phase 3
• Start date: March 12, 2013
• Est. completion date: June 12, 2014

Study information

• Verified date: August 2019
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 508
• Est. completion date: June 12, 2014
• Est. primary completion date: May 22, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Hyperparathyroidism
• Hyperparathyroidism, Secondary
• Kidney Diseases
• Neoplasm Metastasis
• Renal Insufficiency, Chronic

Intervention

Drug:
• Etelcalcetide
Administered intravenously three times per week. The starting dose was 5 mg. The dose may have been increased at 4-week intervals by 2.5 mg or 5 mg on the basis of the predialysis parathyroid hormone and corrected calcium concentrations obtained in the prior week. The minimum dose was 2.5 mg and the maximum dose was 15 mg.
• Placebo
Administered intravenously (IV) three times per week.

Locations

Country	Name	City	State
Australia	Research Site	Liverpool	New South Wales
Australia	Research Site	Parkville	Victoria
Australia	Research Site	Prahan	Victoria
Australia	Research Site	St Leonards	New South Wales
Austria	Research Site	Graz
Austria	Research Site	Linz
Austria	Research Site	Wien
Belgium	Research Site	Aalst
Belgium	Research Site	Baudour
Belgium	Research Site	Bruxelles
Belgium	Research Site	Leuven
Belgium	Research Site	Liège
Canada	Research Site	Brampton	Ontario
Canada	Research Site	Greenfield Park	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Quebec
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Praha 4 - Nusle
Czechia	Research Site	Praha 6
Czechia	Research Site	Slavkov u Brna
Czechia	Research Site	Trinec
France	Research Site	Nantes Cedex 01
France	Research Site	Poitiers
France	Research Site	Reims Cedex
France	Research Site	Saint-Ouen
France	Research Site	Salouel Cedex 1
Germany	Research Site	Berlin
Germany	Research Site	Dresden
Germany	Research Site	Kiel
Germany	Research Site	Villingen-Schwenningen
Hungary	Research Site	Baja
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Gyor
Hungary	Research Site	Kaposvar
Hungary	Research Site	Pecs
Israel	Research Site	Ashkelon
Israel	Research Site	Nahariya
Israel	Research Site	Tel Aviv
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Pavia
Italy	Research Site	San Fermo Della Battaglia (CO)
Italy	Research Site	Verona
Poland	Research Site	Bialystok
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Poland	Research Site	Zamosc
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Spain	Research Site	Barcelona	Cataluña
Spain	Research Site	Barcelona	Cataluña
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Santander	Cantabria
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Coventry
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	London
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Salford
United Kingdom	Research Site	Sheffield
United States	Research Site	Allentown	Pennsylvania
United States	Research Site	Amherst	New York
United States	Research Site	Austin	Texas
United States	Research Site	Azusa	California
United States	Research Site	Birmingham	Alabama
United States	Research Site	Bluefield	West Virginia
United States	Research Site	Bronx	New York
United States	Research Site	Brooklyn	New York
United States	Research Site	Chapel Hill	North Carolina
United States	Research Site	Columbia	Tennessee
United States	Research Site	Covina	California
United States	Research Site	Detroit	Michigan
United States	Research Site	Durham	North Carolina
United States	Research Site	Evanston	Illinois
United States	Research Site	Fairfax	Virginia
United States	Research Site	Fort Worth	Texas
United States	Research Site	Fort Worth	Texas
United States	Research Site	Grand Prairie	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Kalamazoo	Michigan
United States	Research Site	Kansas City	Missouri
United States	Research Site	Lakewood	California
United States	Research Site	Los Angeles	California
United States	Research Site	Lynwood	California
United States	Research Site	Mansfield	Texas
United States	Research Site	Mechanicsville	Virginia
United States	Research Site	Meridian	Idaho
United States	Research Site	Nashville	Tennessee
United States	Research Site	Norfolk	Virginia
United States	Research Site	Northridge	California
United States	Research Site	Ontario	California
United States	Research Site	Orangeburg	South Carolina
United States	Research Site	Panorama City	California
United States	Research Site	Pembroke Pines	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pine Bluff	Arkansas
United States	Research Site	Pontiac	Michigan
United States	Research Site	Reno	Nevada
United States	Research Site	Rosedale	New York
United States	Research Site	Sacramento	California
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	Southgate	Michigan
United States	Research Site	Springfield	Massachusetts
United States	Research Site	Sumter	South Carolina
United States	Research Site	Tupelo	Mississippi
United States	Research Site	Tyler	Texas
United States	Research Site	Whittier	California
United States	Research Site	Yonkers	New York

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Poland,  Russian Federation,  Spain,  United Kingdom, 

References & Publications (9)

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. — View 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. — View 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. — View Citation

Cunningham J, Block GA, Chertow GM, Cooper K, Evenepoel P, Iles J, Sun Y, Ureña-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. — View 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. — View 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. — View Citation

Myles Wolf1, Geoffrey A. Block2, Glenn M. Chertow3, Kerry Cooper4, Bruno Fouqueray4, Sharon M. Moe5, Yan Sun4, Holly Tomlin4, Marc Vervloet 6 and Rainer Oberbauer7. Effects of etelcalcetide on fibroblast growth factor 23 in patients with secondary hyperparathyroidism receiving hemodialysis. Clin Kidney J. 2019;1-10.

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With a > 30% Decrease From Baseline in Mean PTH During the Efficacy Assessment Phase	Participants who did not have any scheduled assessments during the EAP were considered non-responders.	Baseline and the efficacy assessment phase (EAP; defined as Weeks 20 to 27, inclusive).
Secondary	Percentage of Participants With Mean Predialysis Parathyroid Hormone = 300 pg/mL During the Efficacy Assessment Phase	Participants who had no scheduled assessments during the EAP were considered non-responders.	Baseline and the efficacy assessment phase (Week 20 to Week 27)
Secondary	Percent Change From Baseline in Predialysis PTH During the Efficacy Assessment Phase		Baseline and the Efficacy Assessment Phase (Week 20 to Week 27)
Secondary	Percent Change From Baseline in Predialysis Corrected Calcium During the Efficacy Assessment Phase		Baseline and the efficacy assessment phase (Week 20 to Week 27)
Secondary	Percent Change From Baseline in Predialysis Corrected Calcium Phosphorus Product During the Efficacy Assessment Phase		Baseline and the efficacy assessment phase (Week 20 to Week 27)
Secondary	Percent Change From Baseline in Predialysis Phosphorus During the Efficacy Assessment Phase		Baseline and the efficacy assessment phase (Week 20 to Week 27)

External Links

•   AmgenTrials clinical trials website