Efficacy and Safety of Etelcalcetide (AMG 416) in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease (CKD) 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: NCT01788046
• Other study ID #: 20120230
• Secondary ID: KAI-4169-0072012
• Status: Completed
• Phase: Phase 3
• Start date: March 12, 2013
• Est. completion date: May 9, 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 (AMG 416) compared with placebo in the treatment of SHPT in CKD patients receiving hemodialysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 515
• Est. completion date: May 9, 2014
• Est. primary completion date: April 14, 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 agrees to not participate in another study of an investigational agent during the study.

• Subject must be receiving hemodialysis 3 times weekly for at least 3 months

• 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

• 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.

• Subject has a history of any illness that, in the opinion of the Investigator, might confound the results of the study or pose additional risk to the subject.

• 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 weeks 5, 9, 13, and 17 (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	Adelaide	South Australia
Australia	Research Site	Brisbane	Queensland
Australia	Research Site	Clayton	Victoria
Australia	Research Site	Westmead	New South Wales
Belgium	Research Site	Bonheiden
Belgium	Research Site	Brussel
Belgium	Research Site	Brussels
Belgium	Research Site	Liege
Belgium	Research Site	Roeselare
Belgium	Research Site	Tournai
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Halifax	Nova Scotia
Canada	Research Site	Montreal	Quebec
Canada	Research Site	New Westminister	British Columbia
Canada	Research Site	Toronto	Ontario
Czechia	Research Site	Novy Jicin
Czechia	Research Site	Plzen
Czechia	Research Site	Praha 4
Czechia	Research Site	Usti nad Orlici
France	Research Site	Bordeaux Cedex
France	Research Site	Caen
France	Research Site	Grenoble
France	Research Site	Marseille
France	Research Site	Marseille cedex 5
France	Research Site	Perpignan Cedex
Germany	Research Site	Erfurt
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Esztergom
Hungary	Research Site	Kecskemet
Hungary	Research Site	Miskolc
Hungary	Research Site	Zalaegerszeg
Israel	Research Site	Jerusalem
Israel	Research Site	Kfar-Saba
Israel	Research Site	Tel Hashomer
Israel	Research Site	Zerifin
Italy	Research Site	Ancona
Italy	Research Site	Lecco
Italy	Research Site	Milano
Italy	Research Site	Quartu Sant'Elena CA
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Enschede
Netherlands	Research Site	Rotterdam
Netherlands	Research Site	Venlo
Poland	Research Site	Gdansk
Poland	Research Site	Golub-Dobrzyn
Poland	Research Site	Krakow
Poland	Research Site	Lodz
Poland	Research Site	Rybnik
Poland	Research Site	Warszawa
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Yaroslavl
Spain	Research Site	Barcelona	Cataluña
Spain	Research Site	Barcelona	Cataluña
Spain	Research Site	Cordoba	Andalucía
Spain	Research Site	Granada	Andalucía
Spain	Research Site	Majadahonda	Madrid
Sweden	Research Site	Karlstad
Sweden	Research Site	Stockholm
Sweden	Research Site	Uppsala
United States	Research Site	Alexandria	Virginia
United States	Research Site	Arlington	Texas
United States	Research Site	Augusta	Georgia
United States	Research Site	Azusa	California
United States	Research Site	Bethesda	Maryland
United States	Research Site	Beverly Hills	California
United States	Research Site	Brookhaven	Mississippi
United States	Research Site	Brooklyn	New York
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Chicago	Illinois
United States	Research Site	Chula Vista	California
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Columbia	South Carolina
United States	Research Site	Denver	Colorado
United States	Research Site	Detroit	Michigan
United States	Research Site	Eatontown	New Jersey
United States	Research Site	Fairfield	California
United States	Research Site	Fort Washington	Maryland
United States	Research Site	Fresh Meadows	New York
United States	Research Site	Glendale	California
United States	Research Site	Great Neck	New York
United States	Research Site	Gurnee	Illinois
United States	Research Site	Houston	Texas
United States	Research Site	Knoxville	Tennessee
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lauderdale Lakes	Florida
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Los Angeles	California
United States	Research Site	Lubbock	Texas
United States	Research Site	Macon	Georgia
United States	Research Site	Merrillville	Indiana
United States	Research Site	Miami	Florida
United States	Research Site	Mobile	Alabama
United States	Research Site	Morgantown	West Virginia
United States	Research Site	New Bern	North Carolina
United States	Research Site	Northridge	California
United States	Research Site	Norwalk	California
United States	Research Site	Ocala	Florida
United States	Research Site	Riverside	California
United States	Research Site	Rutland	Vermont
United States	Research Site	Shreveport	Louisiana
United States	Research Site	Simi Valley	California
United States	Research Site	Stamford	Connecticut
United States	Research Site	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

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

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 > 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 (cCa x P) 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