Clinical Trial Results:
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
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Summary
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EudraCT number |
2015-005051-28 |
Trial protocol |
DE BE LT GB PL Outside EU/EEA |
Global end of trial date |
31 Oct 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Apr 2019
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First version publication date |
24 Apr 2019
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
20140336
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02833857 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Amgen Inc.
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Sponsor organisation address |
One Amgen Center Drive, Thousand Oaks, CA, United States, 91320
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Public contact |
IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
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Scientific contact |
IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001554-PIP01-13 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Oct 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Oct 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective was to evaluate the safety and tolerability of etelcalcetide after single-dose administration to pediatric subjects 2 to less than 18 years of age with secondary hyperparathyroidism (sHPT) receiving maintenance hemodialysis.
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Protection of trial subjects |
This study was conducted in accordance with International Council for Harmonisation (ICH) Good Clinical Practice (GCP) and applicable national or regional regulations/guidelines.
The study protocol, subject information, informed consent form (ICF), and other written subject information were reviewed and approved by the independent ethics committee (IEC) or institutional review board (IRB) for each study center.
Before a subject’s participation in the clinical study, the investigator was responsible for obtaining written informed consent from the subject’s legally acceptable representative and written assent from the subject (based on local regulations and/or guidelines) after adequate explanation of the aims, methods, anticipated benefits, and potential risks of the study and before any protocol specific screening procedures or investigational product was administered.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Mar 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
Germany: 4
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Country: Number of subjects enrolled |
United Kingdom: 1
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Country: Number of subjects enrolled |
United States: 5
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Worldwide total number of subjects |
11
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EEA total number of subjects |
6
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
5
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Adolescents (12-17 years) |
6
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
This study was conducted at 6 centers in the United States, United Kingdom, and the European Union. Participants were enrolled from 14 March 2017 to 01 October 2018. | ||||||
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Pre-assignment
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Screening details |
Sixteen subjects were screened and 11 subjects were enrolled into the study. | ||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Etelcalcetide | ||||||
Arm description |
Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Etelcalcetide
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Investigational medicinal product code |
AMG 416
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Other name |
Parsabiv
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
All subjects received 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.
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Baseline characteristics reporting groups
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Reporting group title |
Etelcalcetide
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Reporting group description |
Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Etelcalcetide
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Reporting group description |
Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1. | ||
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End point title |
Common Treatment-emergent Adverse Events [1] | ||||||||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
30 days
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical testing was performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline in Serum Corrected Calcium Concentration Over Time [2] | ||||||||||||||||||
End point description |
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]).
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End point type |
Primary
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End point timeframe |
Baseline and Day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study)
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical testing was performed. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change from Baseline in Serum Phosphorus Concentration at End of Study [3] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline and day 30 (end of study)
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical testing was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from Baseline in Serum Potassium Concentration at End of Study [4] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline and day 30 (end of study)
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical testing was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from Baseline in Intact Parathyroid Hormone (iPTH) Levels Over Time [5] | ||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline and day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study)
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical testing was performed. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change from Baseline in Heart Rate at End of Study [6] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline and day 30 (end of study)
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| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical testing was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from Baseline in Temperature at End of Study [7] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline and day 30 (end of study)
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical testing was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from Baseline in Blood Pressure at End of Study [8] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline and day 30 (end of study)
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| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical testing was performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline in PR Interval at End of Study [9] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline and day 30 (end of study)
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| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical testing was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from Baseline in QRS Interval at End of Study [10] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline and day 30 (end of study)
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| Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical testing was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from Baseline in QT Interval at End of Study [11] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline and day 30 (end of study)
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| Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical testing was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from Baseline in Corrected (Bazett) QT Interval at End of Study [12] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline and day 30 (end of study)
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| Notes [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical testing was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from Baseline in Corrected (Fridericia) QT Interval at End of Study [13] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline and day 30 (end of study)
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| Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical testing was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from Baseline in Serum Total Calcium Concentration Over Time | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline and Day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study)
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change from Baseline in Serum Ionized Calcium Concentration Over Time | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline and Day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study)
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Maximum Observed Plasma Concentration (Cmax) of Etelcalcetide | ||||||||
End point description |
Plasma etelcalcetide concentrations were measured using a validated high performance liquid chromatography assay. The lower limit of quantitation was 0.200 ng/mL.
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End point type |
Secondary
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End point timeframe |
10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Maximum Concentration (Tmax) of Etelcalcetide | ||||||||
End point description |
Plasma etelcalcetide concentrations were measured using a validated high performance liquid chromatography assay. The lower limit of quantitation was 0.200 ng/mL.
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End point type |
Secondary
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End point timeframe |
10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose
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| No statistical analyses for this end point | |||||||||
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End point title |
Area Under the Plasma Etelcalcetide Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | ||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose
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| No statistical analyses for this end point | |||||||||
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End point title |
Area Under the Plasma Etelcalcetide Concentration-Time Curve From Time Zero Infinity (AUCinf) | ||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose
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| No statistical analyses for this end point | |||||||||
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End point title |
Terminal Half-life (T1/2,z) of Etelcalcetide | ||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants Who Developed Anti-etelcalcetide Binding Antibodies | ||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline and day 30
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants with Treatment-emergent Adverse Events | ||||||||||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
30 days
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| No statistical analyses for this end point | |||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
30 days
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.0
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Reporting groups
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Reporting group title |
Etelcalcetide
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Reporting group description |
Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
