Secondary Hyperparathyroidism

Primary • 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 Secondary • To characterize PK of etelcalcetide treatment • To characterize the safety of etelcalcetide treatment • To characterize change in laboratory markers of CKD following etelcalcetide treatment

Parsabiv

AMG 416 (etelcalcetide)

solution for IV

5 mg/mL, 2 ml/vial

Primary Outcome Measures :
Change of intact parathyroid hormone (iPTH) levels in children ages 28d to <18y with secondary hyperparathyroidism (sHPT) receiving maintenance hemodialysis [ Time Frame: 32 weeks ]
Achievement of at least a 30% reduction from baseline in mean iPTH during the efficacy assessment phase (EAP)


Secondary Outcome Measures :
Corrected serum calcium levels of < 8.0 mg/dL in children aged 2 years to <18 years old [ Time Frame: 32 weeks ]
To characterize the safety of etelcalcetide treatment

Corrected serum calcium levels of < 8.6 mg/dL in children aged 28 days to <18 years old [ Time Frame: 32 weeks ]
To characterize the safety of etelcalcetide treatment

Inclusion Criteria
Subjects are eligible to be included in the study only if all of the following criteria apply:
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.

Exclusion Criteria
Subjects are excluded from the study if any of the following criteria apply.
Disease Related
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.
Other Medical Conditions
205. History of other malignancy, except non-melanoma skin cancers, cervical or
breast ductal carcinoma in situ within the last 5 years.
Prior/Concomitant Therapy
206. Use of concomitant medications that may prolong the corrected QT interval
(eg, ondansetron, albuterol, sotalol, amiodarone, erythromycin, or
clarithromycin). Refer to CredibleMeds.org for guidance.
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.
209. All herbal medicines (eg, St. John’s wort), vitamins, and supplements
consumed by the subject within the 30 days prior to randomization, 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 randomization 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 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.
Diagnostic Assessments During Screening
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.
Other Exclusions
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. Refer to Appendix 5 for additional contraceptive
information.
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 (with the exception of those outlined above) that, in the opinion of the
investigator or Amgen physician, if consulted, would pose a risk to subject
safety or interfere with the study evaluation, procedures or completion.
223. Subject has previously entered this study.