A Single-dose Study in Paediatric Patients Aged 2 to Less Than 18 Years With Secondary Hyperparathyroidism (sHPT) Receiving Haemodialysis

An Open-label, Single-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Etelcalcetide (AMG 416) in Paediatric Subjects Aged 2 to Less Than 18 Years With Secondary Hyperparathyroidism (sHPT) Receiving Maintenance Haemodialysis

This is a study to evaluate the safety and pharmacokinetics in pediatric patients with secondary hyperparathyroidism receiving a single dose of etelcalcetide at the end of hemodialysis.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease, Secondary Hyperparathyroidism
• Intervention / Treatment: Drug: Etelcalcetide

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1020
    • Research Site
  • Gent, Belgium, 9000
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
• Germany
  • Hannover, Germany, 30625
    • Research Site
  • Heidelberg, Germany, 69120
    • Research Site
  • Köln, Germany, 50937
    • Research Site
  • Marburg, Germany, 35043
    • Research Site
• Lithuania
  • Vilinus, Lithuania, 08406
    • Research Site
• Poland
  • Krakow, Poland, 30-663
    • Research Site
• United Kingdom
  • London, United Kingdom, WC1N 3JH
    • Research Site
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject's parent has provided informed consent and subject has provided assent
• Children Age 2 to less than 18 years
• Diagnosed with chronic kidney disease
• Diagnosed with secondary hyperparathyroidism receiving hemodialysis,
• Weighing at least 7 kg
• Laboratory results within specified range.

Exclusion Criteria:

• Currently receiving treatment in another investigation device or drug study
• Subject has received cinacalcet therapy within 30 days
• History of prolongation QT interval
• Subject is taking any medications that are on the QT prolongation medication list
• Electrocardiograph (ECG) measurements within specified range.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Etelcalcetide; Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.	Drug: Etelcalcetide; A single IV-bolus dose of 0.035 mg/kg etelcalcetide into the venous line of the dialysis circuit at the end of a hemodialysis session.; Other Names: Parsabiv; AMG 416

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Common Treatment-emergent Adverse Events	A treatment-emergent adverse event is any adverse event (AE) that begins or worsens after the initial dose of study drug (etelcalcetide) and up to 30 days after the last dose. Common adverse events were defined as adverse events occurring in at least 2 participants. The Medical Dictionary for Regulatory Activities (MedDRA) version 21.0 was used for coding all adverse events.	30 days
Change From Baseline in Serum Corrected Calcium Concentration Over Time	When albumin was less than 4.0 mg/dL, the calcium concentration was corrected according to the formula: cCa (mmol/L) = measured total serum calcium (mmol/L) + 0.02 (40 - serum albumin [g/L]).	Baseline and Day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study)
Change From Baseline in Serum Phosphorus Concentration at End of Study		Baseline and day 30 (end of study)
Change From Baseline in Serum Potassium Concentration at End of Study		Baseline and day 30 (end of study)
Change From Baseline in Intact Parathyroid Hormone (iPTH) Levels Over Time		Baseline and day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study)
Change From Baseline in Heart Rate at End of Study		Baseline and day 30 (end of study)
Change From Baseline in Temperature at End of Study		Baseline and day 30 (end of study)
Change From Baseline in Blood Pressure at End of Study		Baseline and day 30 (end of study)
Change From Baseline in PR Interval at End of Study		Baseline and day 30 (end of study)
Change From Baseline in QRS Interval at End of Study		Baseline and day 30 (end of study)
Change From Baseline in QT Interval at End of Study		Baseline and day 30 (end of study)
Change From Baseline in Corrected (Bazett) QT Interval at End of Study		Baseline and day 30 (end of study)
Change From Baseline in Corrected (Fridericia) QT Interval at End of Study		Baseline and day 30 (end of study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Serum Total Calcium Concentration		Baseline and Day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study)
Change From Baseline in Serum Ionized Calcium Concentration		Baseline and Day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study)
Maximum Observed Plasma Concentration (Cmax) of Etelcalcetide	Plasma etelcalcetide concentrations were measured using a validated high performance liquid chromatography assay. The lower limit of quantitation was 0.200 ng/mL.	10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose
Time to Maximum Concentration (Tmax) of Etelcalcetide	Plasma etelcalcetide concentrations were measured using a validated high performance liquid chromatography assay. The lower limit of quantitation was 0.200 ng/mL.	10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose
Area Under the Plasma Etelcalcetide Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Plasma etelcalcetide concentrations were measured using a validated high performance liquid chromatography assay. The lower limit of quantitation was 0.200 ng/mL. Area under the curve for plasma etelcalcetide from time zero to the last quantifiable concentration (AUClast) was estimated using the linear trapezoidal method.	10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose
Area Under the Plasma Etelcalcetide Concentration-Time Curve From Time Zero Infinity (AUCinf)	Plasma etelcalcetide concentrations were measured using a validated high performance liquid chromatography assay. The lower limit of quantitation was 0.200 ng/mL. Area under the concentration-time curve from time zero to infinite time (AUCinf) was estimated using the linear trapezoidal method.	10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose
Terminal Half-life (T1/2,z) of Etelcalcetide	Plasma etelcalcetide concentrations were measured using a validated high performance liquid chromatography assay. The lower limit of quantitation was 0.200 ng/mL. Terminal half life of plasma etelcalcetide (t1/2,z) was calculated as t1/2,z = ln(2)/λz, where λz is the first-order terminal rate constant estimated by linear regression of the terminal log-linear phase.	10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose
Number of Participants Who Developed Anti-etelcalcetide Binding Antibodies	Samples were collected predose and at end of study (day 30) and tested for anti etelcalcetide binding antibodies using a validated immunoassay. Developing antibody binding was defined as participants who were binding antibody positive postbaseline with a negative result at baseline.	Baseline and day 30
Number of Participants With Treatment-emergent Adverse Events	A treatment-emergent adverse event is any adverse event that begins or worsens after the initial dose of study drug (etelcalcetide) and up to 30 days after the last dose. The severity of each adverse event was graded using the National Cancer Institute-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, where Grade 1 = Mild (asymptomatic or mild symptoms), Grade 2 = Moderate (minimal, local or noninvasive intervention indicated), Grade 3 = Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated, Grade 4 = Life-threatening consequences; urgent intervention indicated, and Grade 5 = Death related to AE.	30 days

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Sohn W, Salusky IB, Schmitt CP, Taylan C, Walle JV, Ngang J, Yan L, Kroenke M, Warady BA. Phase 1, single-dose study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of etelcalcetide in pediatric patients with secondary hyperparathyroidism receiving hemodialysis. Pediatr Nephrol. 2021 Jan;36(1):133-142. doi: 10.1007/s00467-020-04599-z. Epub 2020 Jul 9.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 14, 2017
• Primary Completion (ACTUAL): October 31, 2018
• Study Completion (ACTUAL): October 31, 2018

Study Registration Dates

• First Submitted: June 9, 2016
• First Submitted That Met QC Criteria: July 12, 2016
• First Posted (ESTIMATE): July 14, 2016

Study Record Updates

• Last Update Posted (ACTUAL): July 10, 2019
• Last Update Submitted That Met QC Criteria: April 23, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Secondary Hyperparathyroidism, chronic kidney disease, hemodialysis
• 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
• Other Study ID Numbers: 20140336; 2015-005051-28 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No