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

• ClinicalTrials.gov Identifier: NCT02833857
• Recruitment Status: Completed
• First Posted: July 14, 2016
• Results First Posted: July 10, 2019
• Last Update Posted: July 10, 2019
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: June 9, 2016
• First Posted Date: July 14, 2016
• Results First Submitted Date: April 23, 2019
• Results First Posted Date: July 10, 2019
• Last Update Posted Date: July 10, 2019
• Actual Study Start Date: March 14, 2017
• Actual Primary Completion Date: October 31, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 23, 2019)

• Common Treatment-emergent Adverse Events [ Time Frame: 30 days ]
  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.
• Change From Baseline in Serum Corrected Calcium Concentration Over Time [ Time Frame: Baseline and Day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study) ]
  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]).
• Change From Baseline in Serum Phosphorus Concentration at End of Study [ Time Frame: Baseline and day 30 (end of study) ]
• Change From Baseline in Serum Potassium Concentration at End of Study [ Time Frame: Baseline and day 30 (end of study) ]
• Change From Baseline in Intact Parathyroid Hormone (iPTH) Levels Over Time [ Time Frame: 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 [ Time Frame: Baseline and day 30 (end of study) ]
• Change From Baseline in Temperature at End of Study [ Time Frame: Baseline and day 30 (end of study) ]
• Change From Baseline in Blood Pressure at End of Study [ Time Frame: Baseline and day 30 (end of study) ]
• Change From Baseline in PR Interval at End of Study [ Time Frame: Baseline and day 30 (end of study) ]
• Change From Baseline in QRS Interval at End of Study [ Time Frame: Baseline and day 30 (end of study) ]
• Change From Baseline in QT Interval at End of Study [ Time Frame: Baseline and day 30 (end of study) ]
• Change From Baseline in Corrected (Bazett) QT Interval at End of Study [ Time Frame: Baseline and day 30 (end of study) ]
• Change From Baseline in Corrected (Fridericia) QT Interval at End of Study [ Time Frame: Baseline and day 30 (end of study) ]

Original Primary Outcome Measures (submitted: July 12, 2016)

• Common Treatment emergent AEs [ Time Frame: 30 days ]
• Changes in Key Laboratory Tests [ Time Frame: 30 days ]
• Changes in ECG [ Time Frame: 30 days ]
• Changes in Vital Signs [ Time Frame: 30 days ]

Current Secondary Outcome Measures (submitted: April 23, 2019)

• Change From Baseline in Serum Total Calcium Concentration [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose ]
  Plasma etelcalcetide concentrations were measured using a validated high performance liquid chromatography assay. The lower limit of quantitation was 0.200 ng/mL.
• Time to Maximum Concentration (Tmax) of Etelcalcetide [ Time Frame: 10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose ]
  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 Plasma Etelcalcetide Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) [ Time Frame: 10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose ]
  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.
• Area Under the Plasma Etelcalcetide Concentration-Time Curve From Time Zero Infinity (AUCinf) [ Time Frame: 10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose ]
  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.
• Terminal Half-life (T1/2,z) of Etelcalcetide [ Time Frame: 10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose ]
  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.
• Number of Participants Who Developed Anti-etelcalcetide Binding Antibodies [ Time Frame: Baseline and day 30 ]
  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.
• Number of Participants With Treatment-emergent Adverse Events [ Time Frame: 30 days ]
  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.

Original Secondary Outcome Measures (submitted: July 12, 2016)

• AUC (PK parameter) [ Time Frame: 30 days ]
• Concentration of parathyroid hormone (PTH) (PD parameter) [ Time Frame: 30 days ]
• Anti-drug antibodies [ Time Frame: 30 days ]
• Treatment emergent AEs [ Time Frame: 30 days ]
• Cmax (PK parameter) [ Time Frame: 30 days ]
• Tmax (PK parameter) [ Time Frame: 30 days ]
• Serum calcium [total calcium, ionized calcium and albumin corrected calcium] over time (PD parameter) [ Time Frame: 30 days ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Single-dose Study in Paediatric Patients Aged 2 to Less Than 18 Years With Secondary Hyperparathyroidism (sHPT) Receiving Haemodialysis
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Chronic Kidney Disease, Secondary Hyperparathyroidism

Intervention

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:

• AMG 416
• Parsabiv

Study Arms

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.

Intervention: Drug: Etelcalcetide

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 29, 2018): 11
• Original Estimated Enrollment (submitted: July 12, 2016): 1
• Actual Study Completion Date: October 31, 2018
• Actual Primary Completion Date: October 31, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Germany, Lithuania, Poland, United Kingdom, United States

Administrative Information

• NCT Number: NCT02833857
• Other Study ID Numbers: 20140336; 2015-005051-28 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• 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.
• 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.
• URL: https://www.amgen.com/datasharing

• Current Responsible Party: Amgen
• Original Responsible Party: Same as current
• Current Study Sponsor: Amgen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: April 2019