A Phase 3 Study of Etelcalcetide in Children With Secondary Hyperparathyroidism Receiving Hemodialysis

Phase 1

• Conditions: Secondary Hyperparathyroidism (sHPT) Receiving Maintenance Haemodialysis; MedDRA version: 20.0Level: PTClassification code 10020708Term: Hyperparathyroidism secondarySystem Organ Class: 10014698 - Endocrine disorders; Therapeutic area: Diseases [C] - Hormonal diseases [C19]

• Registration Number: EUCTR2018-004608-21-GR
• Lead Sponsor: Amgen Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-06-25
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 20

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 = 2 to < 18 years of age at the time of enrollment.
103. Dry weight = 7 kg at the time of screening.
104. Diagnosed with CKD and SHPT undergoing hemodialysis/hemodiafiltration TIW at the time of screening =1 month.
105. Diagnosis of SHPT with the mean of the 2 consecutive central laboratory iPTH values > 300 pg/mL (33 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) obtained from the central laboratory during screening.
107. Dialysate Ca level = 2.5 mEq/L for at least 1 month prior to screening and throughout the duration of the study.
108. Subject receiving active vitamin D sterols must have had no more than a maximum dose change of 50% within the 2 weeks prior to screening laboratory assessments, remain stable through enrollment, 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 no more than a maximum
dose change of 50% within the 2 weeks prior to screening laboratory assessments, remain stable through enrollment, 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 no more than a maximum dose change of 50% within the 2 weeks prior to screening laboratory assessments, remain stable through enrollment, 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 20
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

201. History of congenital long QT syndrome, second or third degree heart block, ventricular tachyarrhythmia’s, history of symptomatic ventricular dysrhythmias Torsades de Pointes 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 enrollment.
205. Current malignancy or history of other malignancy, except non-melanoma skin cancers within the last 5 years.
Prior/Concomitant Therapy
206. Use of concomitant medications that may prolong the QTc (eg, ondansetron, albuterol, sotalol, amiodarone, erythromycin, or clarithromycin).
207. Receipt of cinacalcet therapy within 30 days prior to screening and through enrollment.
208. Any previous use of etelcalcetide prior to screening and through enrollment.
209. All herbal medicines (eg, St. John’s wort), vitamins, and supplements consumed by the subject within the 30 days prior to enrollment, and continuing use if applicable, will be reviewed by the Principal Investigator and the Amgen Medical
Monitor. Written documentation of the review and Amgen acknowledgment is required for subject participation.
210. Use of any over-the-counter or prescription medications within the 14 days or 5 half-lives (whichever is longer) prior to enrollment 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 the review and Amgen acknowledgment is required for subject participation. Paracetamol (up to 2 g per day) for analgesia
will be allowed. Prior/Concurrent Clinical Study Experience
211. Currently receiving treatment in another investigational device or drug study, or less than 30 days 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 aminotransferase [ALT] or serum glutamic pyruvic transaminase [SGPT], aspartate aminotransferase [AST], or serum glutamic oxaloacetic transaminase [SGOT]) > 1.5 times the upper limit of normal (ULN).
213. Corrected QT interval > 500 ms, using Bazett’s formula
214. Corrected QT interval = 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 (eg, unstable arrhythmia) during screening that, in the opinion of the investigator, could pose a risk to subject safety or interfere with the study evaluation.
216. New onset or worsening of a pre-existing seizure disorder.
217. Subjects on anti-convulsant medication must be on a stable and therapeutic dose for 3 months prior to screening (if blood level monitoring is clinically available, then the subject must have a therapeutic blood level within 1 week of enrollment).
218. Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 3 months after the last dose of etelcalcetide. (Female

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of etelcalcetide in reducing the intact parathyroid hormone (iPTH) level in children ages = 2 to < 18 years with secondary hyperparathyroidism (SHPT) receiving maintenance hemodialysis.;Secondary Objective: To evaluate the efficacy of etelcalcetide in reducing the iPTH level by > 30%.<br>To characterize change in laboratory markers of chronic kidney disease (CKD) following etelcalcetide treatment.<br>To characterize the safety of etelcalcetide treatment based on laboratory values.<br>To characterize the pharmacokinetic (PK) of etelcalcetide treatment after single and multiple doses.;Primary end point(s): • Percent change in iPTH from baseline during the efficacy assessment period (EAP) at weeks 20 to 26.;Timepoint(s) of evaluation of this end point: Day 1, Week 20, 21, 22, 23, 24, 25 and 26.