E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Secondary Hyperparathyroidism (sHPT) Receiving Maintenance Haemodialysis |
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E.1.1.1 | Medical condition in easily understood language |
Secondary Hyperparathyroidism (sHPT) |
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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 |
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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 efficacy of etelcalcetide in reducing the intact parathyroid hormone level (iPTH) by ≥ 30% in children ages 28 days to < 18 years with secondary hyperparathyroidism (SHPT) receiving maintenance hemodialysis. |
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E.2.2 | Secondary objectives of the trial |
• To characterize PK of etelcalcetide treatment • To characterize the safety of etelcalcetide treatment • To characterize change in laboratory markers of CKD following etelcalcetide treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
101. Subject’s legally acceptable representative has provided informed consent when the subject is legally too young to provide 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. 102. Male or female subjects 28 days to < 18 years of age at the time of enrollment. 103. Dry weight ≥ 7 kg during screening. 104. Diagnosed with CKD and SHPT undergoing hemodialysis at the time of screening (subjects 6 months or older should have been receiving hemodialysis for ≥ 1 month; no specific duration of current hemodialysis history is required for subjects 28 days to < 6 months of age – only need to be undergoing hemodialysis at time of screening). 105. Diagnosis of SHPT with the mean of the 2 consecutive central laboratory iPTH values ≥ 400 pg/mL (42 pmol/L) during screening, on separate days and within 2 weeks of enrollment obtained from the central laboratory during screening. 106. Serum cCa value ≥ 9.0 mg/dL (2.25 mmol/L) for subjects ≥ 2 years of age and older and serum cCa value ≥ 9.6 mg/dL (2.4 mmol/L) for subjects 28 days to < 2 years of age obtained from the central laboratory during screening. 107. Dialysate Ca level ≥ 2.5 mEq/L during screening. 108. Subject receiving active vitamin D sterols must have had a stable dose within the 2 weeks prior to screening laboratory assessments, remain stable through randomization, and be expected to maintain stable doses for the duration of the study, except for adjustments allowed per protocol. 109. Subject receiving phosphate binders must have had a stable dose within the 2 weeks prior to screening laboratory assessments, remain stable through randomization, and be expected to maintain stable dose for the duration of the study, except for adjustments allowed per protocol. 110. Subject receiving Ca supplements must have had a stable dose within the 2 weeks prior to screening laboratory assessments and remain stable through randomization and be expected to maintain stable dose for the duration of the study, except for adjustments allowed per protocol. 111. SHPT not due to vitamin D deficiency, per investigator assessment.
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E.4 | Principal exclusion criteria |
201. History of congenital long QT syndrome, second or third degree heart block, ventricular tachyarrhythmia’s or other conditions associated with prolonged QT interval. 202. Anticipated or scheduled parathyroidectomy during the study period. 203. Anticipated or scheduled kidney transplant during the study period. 204. Subject has received a parathyroidectomy within 6 months prior to randomization 205. History of other malignancy, except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years. 206. Use of concomitant medications that may prolong the corrected QT interval (eg, ondansetron, albuterol, sotalol, amiodarone, erythromycin, or clarithromycin). 207. Receipt of cinacalcet therapy within 30 days prior to screening assessments and through randomization. 208. Receipt of etelcalcetide within 6 months prior to screening assessments and through randomization. 211. Currently receiving treatment in another investigational device or drug study, or less than 30 days or 5 half-lives (whichever is longer) since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded. 212. Subject has significant abnormalities on the most recent central laboratory test during the screening period prior to enrollment per the Investigator including but not limited to the following: a. Serum transaminase (alanine aminotransaminase [ALT] or serum glutamic pyruvic transaminase [SGPT], aspartate aminotransferase [AST] or serum glutamic oxaloacetic transaminase [SGOT]) > 2.0 times the upper limit of normal (ULN). 213. Corrected QT interval (QTc) > 500 ms, using Bazett’s formula. 214. QTc ≥ 450 to ≤ 500 ms, using Bazett’s formula, unless written permission to enroll is provided by the investigator after consultation with a pediatric cardiologist. 215. Subject has a clinically significant electrocardiogram (ECG) abnormality during screening that, in the opinion of the investigator, could pose a risk to subject safety or interfere with the study evaluation. Within the 60 days prior to enrollment 216. New onset or worsening of a pre-existing seizure disorder. 217. Subjects aged 28 days to 6 months of age who were born prematurely at < 36 weeks gestational age. 218. Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 30 days after the last dose of etelcalcetide. (Females of childbearing potential should only be included in the study after a confirmed menstrual period and a negative serum pregnancy test within 7 days prior to the first dose of investigational product). 219. Female subjects of childbearing potential unwilling to use 1 highly effective method of contraception or acceptable method of effective contraception during treatment and for an additional 30 days after the last dose of investigational product. 220. Subject has known sensitivity to etelcalcetide or excipients to be administered during dosing. 221. Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, to the best of the subject and investigator’s knowledge). 222. History or evidence of any other clinically significant disorder, condition or disease 223. Subject has previously entered this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Achievement of at least a 30% reduction from baseline in mean iPTH during the efficacy assessment phase (EAP)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Cmax and Cmin • Nature, frequency, severity, and relationship to treatment of all adverse events, including those of special interest reported during the study • Frequency of hypocalcemia • Occurrence of corrected serum Ca levels < 8.0 mg/dL (2.0 mmol/L) for subjects 2 to < 18 year of age and <8.6 mg/dL (2.15 mmol/L) for subjects 28 days to < 2 years of age during the study • Changes in laboratory parameters at scheduled visits • Percent change from baseline in predialysis iPTH during the EAP • Percent change in corrected total serum Ca and serum phosphorus from baseline during the EAP
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Cmax/Cmin - D1, W5, W9, W13, W17, W27, EOS EAP - W20-27 all others anytime during the study |
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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 | Yes |
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 | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Argentina |
India |
Korea, Republic of |
Malaysia |
Russian Federation |
Singapore |
Taiwan |
Turkey |
Ukraine |
United States |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |