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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01788046




Registration number
NCT01788046
Ethics application status
Date submitted
7/02/2013
Date registered
11/02/2013
Date last updated
20/08/2019

Titles & IDs
Public title
Efficacy and Safety of Etelcalcetide (AMG 416) in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease (CKD) on Hemodialysis
Scientific 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
Secondary ID [1] 0 0
KAI-4169-007
Secondary ID [2] 0 0
20120230
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hyperparathyroidism, Secondary 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Etelcalcetide
Treatment: Drugs - Placebo

Placebo comparator: Placebo - Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.

Experimental: Etelcalcetide - Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW for 26 weeks.


Treatment: Drugs: 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.

Treatment: Drugs: Placebo
Administered intravenously (IV) three times per week.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With > 30% Decrease From Baseline in Mean PTH During the Efficacy Assessment Phase
Timepoint [1] 0 0
Baseline and the efficacy assessment phase (EAP; defined as Weeks 20 to 27, inclusive).
Secondary outcome [1] 0 0
Percentage of Participants With Mean Predialysis Parathyroid Hormone = 300 pg/mL During the Efficacy Assessment Phase
Timepoint [1] 0 0
Baseline and the efficacy assessment phase (Week 20 to Week 27)
Secondary outcome [2] 0 0
Percent Change From Baseline in Predialysis PTH During the Efficacy Assessment Phase
Timepoint [2] 0 0
Baseline and the Efficacy Assessment Phase (Week 20 to Week 27)
Secondary outcome [3] 0 0
Percent Change From Baseline in Predialysis Corrected Calcium During the Efficacy Assessment Phase
Timepoint [3] 0 0
Baseline and the efficacy assessment phase (Week 20 to Week 27)
Secondary outcome [4] 0 0
Percent Change From Baseline in Predialysis Corrected Calcium Phosphorus Product (cCa x P) During the Efficacy Assessment Phase
Timepoint [4] 0 0
Baseline and the efficacy assessment phase (Week 20 to Week 27)
Secondary outcome [5] 0 0
Percent Change From Baseline in Predialysis Phosphorus During the Efficacy Assessment Phase
Timepoint [5] 0 0
Baseline and the efficacy assessment phase (Week 20 to Week 27)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/03/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/05/2014
Sample size
Target
Accrual to date
Final
515
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Research Site - Westmead
Recruitment hospital [2] 0 0
Research Site - Brisbane
Recruitment hospital [3] 0 0
Research Site - Adelaide
Recruitment hospital [4] 0 0
Research Site - Clayton
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4102 - Brisbane
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment outside Australia
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United States of America
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Alabama
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California
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Colorado
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Connecticut
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Illinois
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Indiana
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Kansas
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Louisiana
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Maryland
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Michigan
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Mississippi
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Nebraska
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Vermont
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West Virginia
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Bonheiden
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Jerusalem
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Kfar-Saba
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Tel Hashomer
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Israel
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Zerifin
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Ancona
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Lecco
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Amsterdam
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Enschede
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Rotterdam
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Venlo
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Gdansk
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Golub-Dobrzyn
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Lodz
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Rybnik
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Russian Federation
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Moscow
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Saint Petersburg
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Yaroslavl
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Cataluña
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Madrid
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Karlstad
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Stockholm
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Sweden
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Uppsala

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT01788046
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01788046