E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Secondary Hyperparathyroidism (sHPT) Receiving Maintenance Haemodialysis |
|
E.1.1.1 | Medical condition in easily understood language |
Secondary Hyperparathyroidism (sHPT) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020708 |
E.1.2 | Term | Hyperparathyroidism secondary |
E.1.2 | System Organ Class | 10014698 - Endocrine disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of etelcalcetide after single dose administration to paediatric subjects aged 2 to less than 18 years with secondary hyperparathyroidism (sHPT) receiving maintenance haemodialysis |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the pharmacokinetic profile of plasma etelcalcetide, serum PTH and serum calcium (total calcium, ionized calcium and albumin corrected calcium) levels following single intravenous (IV) administration of etelcalcetide. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject’s legally acceptable representative has provided informed consent and
the subject has provided written assent based on local regulations and/or
guidelines prior to any study-specific activities/procedures being initiated.
2. Male or female subjects (aged 2 to less than 18 years) diagnosed with CKD and
sHPT and receiving maintenance haemodialysis or haemodiafiltration for
> 30 days prior to screening.
3. Subject must be on a dialysate calcium concentration of ≥ 2.5 mEq/L
(1.25 mmol/L) for at least 1 month prior to enrollment and throughout the duration of the study.
4. Screening and Baseline serum PTH level > 200 pg/mL (21 pmol/L).
5. Subject must weigh ≥ 7 kg at Baseline (Day -2).
6. Screening and Baseline serum corrected calcium from the local laboratory
≥ 9 mg/dL (2.25 mmol/L).
7. Subjects on anti-convulsant medication must be on a stable dose for 3 months.
8. Free of any disease or condition other than those diseases or conditions related to their renal disease that, in the opinion of the investigator, would impact the subject’s safety or the integrity of the study data. |
|
E.4 | Principal exclusion criteria |
1. Currently receiving or has received any investigational drug (or is currently using an investigational device) within the 30 days or 5 half-lives (whichever is longer), prior to receiving the first dose of etelcalcetide. Other investigational procedures while participating in this study are excluded.
2. Subject previously has entered this study or previously exposed to etelcalcetide.
3. All herbal medicines (eg, St. John’s wort), vitamins, and supplements consumed by the subject within the 30 days prior to receiving the first dose of etelcalcetide, and continuing use if applicable, will be reviewed by the Principal Investigator and the Amgen Medical Monitor. Written documentation of this review and Amgen acknowledgment is required for subject participation.
4. Use of any over-the-counter or prescription medications within the 14 days or
5 half-lives (whichever is longer) prior to receiving the first dose of etelcalcetide
that are not established therapies for subjects with renal disease or other
conditions secondary to renal disease will be reviewed by the Principal
Investigator and the Amgen Medical Monitor. Written documentation of this
review and Amgen acknowledgment is required for subject participation.
Paracetamol (up to 2 g per day) for analgesia will be allowed.
5. Malignancy except non-melanoma skin cancers,within the last 5 years.
6. History of hypersensitivity or allergic reaction to any of the excipients listed in
Section 6.2.1.
7. Subject received cinacalcet therapy within less than 30 days prior to etelcalcetide dosing.
8. A new onset of seizure or worsening of a pre-existing seizure disorder within
2 months prior to etelcalcetide administration.
9. Subject’s screening 12-lead ECG suggests unstable arrhythmia or other cardiac
abnormality that could place the subject at increased risk, based upon the
Investigator’s opinion.
10. History of prolongation of the QT interval (eg, congenital long QT interval,
second or third degree heart block or other conditions which prolong the QT
interval) or history of ventricular arrhythmias.
11. Concurrent or within 28 days prior to enrollment use of medications that prolong QT interval (eg, sotalol, amiodarone, erythromycin, or clarithromycin). Please refer to the complete QT prolongation medication list at
http://www.crediblemeds.org/pdftemp/pdf/CompositeList.pdf
12. Subjects with a corrected QT Interval (QTc) > 500 ms during screening, using
Bazett’s formula.
13. Subject has a history of symptomatic ventricular dysrhythmias or Torsades de
Pointes.
14. Subject has a screening ALT or AST from the local lab ≥ 1.5 times the upper limit of normal (ULN).
15. Female subjects of childbearing potential who are unwilling to practice true
sexual abstinence or use an acceptable method(s) of effective birth control
during treatment through 3 months after receiving the etelcalcetide.
16. Post-menarchal subject who is pregnant or breastfeeding, or is planning to
become pregnant or breastfeed during treatment and for an additional 3 months
after etelcalcetide administration. Female subjects with a positive pregnancy test
at screening.
17. Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator’s knowledge. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Common treatment-emergent adverse events [including changes in physical
examinations]
• Changes in key laboratory safety tests [albumin corrected calcium (cCalcium),
phosphorus, potassium, parathyroid hormone (PTH)], ECGs and vital signs |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Pharmacokinetic parameters (AUC, Cmax, tmax, t1/2) of etelcalcetide in plasma
• Pharmacodynamics: concentration of parathyroid hormone (PTH), serum calcium
[total calcium, ionized calcium and albumin corrected calcium] over time
• Anti-etelcalcetide antibodies
• Incidence of treatment-emergent adverse events |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Phase 1b Open-label, Single-Dose Study in paediatric subjects |
|
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Czech Republic |
France |
Germany |
Lithuania |
Poland |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 15 |