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

Inclusion Criteria:

• Subject's legally acceptable representative has provided informed consent when thesubject is legally too young to provide informed consent and the subject hasprovided written assent based on local regulations and/or guidelines prior to anystudy-specific activities/procedures being initiated.

• Male or female subjects greater than or equal to 2 to less than 18 years of age atthe time of enrollment.

• Targeted Dry weight greater than or equal to 7 kg at the time of screening Week -1.

• Diagnosed with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT)undergoing hemodialysis/hemodiafiltration three times per week (TIW) at the time ofscreening greater than or equal to 1 month.

• Diagnosis of secondary hyperparathyroidism (SHPT) with the mean of the 2 consecutivecentral laboratory intact parathyroid hormone (iPTH) values greater than 300 pg/mLduring screening, on separate days and within 2 weeks of enrollment obtained fromthe central laboratory during screening.

• Serum corrected calcium (cCa) value greater than or equal to 9.0 mg/dL obtained fromthe central laboratory during screening.

• Dialysate calcium (Ca) level greater than or equal to 2.5 mEq/L for at least 1 monthprior to screening and throughout the duration of the study.

• Subject receiving active vitamin D sterols must have had no more than a maximum dosechange of 50% within the 2 weeks prior to screening laboratory assessments, remainstable through enrollment, and be expected to maintain stable doses for the durationof the study, except for adjustments allowed per protocol.

• Subject receiving phosphate binders must have had no more than a maximum dose changeof 50% within the 2 weeks prior to screening laboratory assessments, remain stablethrough enrollment, and be expected to maintain stable dose for the duration of thestudy, except for adjustments allowed per protocol.

• Subject receiving calcium (Ca) supplements must have had no more than a maximum dosechange of 50% within the 2 weeks prior to screening laboratory assessments, remainstable through enrollment, and be expected to maintain stable dose for the durationof the study, except for adjustments allowed per protocol.

• Secondary hyperparathyroidism (SHPT) not due to vitamin D deficiency, perinvestigator assessment.

Exclusion Criteria:

• Disease Related:

• History of congenital long QT syndrome, second or third degree heart block,ventricular tachyarrhythmia's, history of symptomatic ventricular dysrhythmiasTorsades de Pointes or other conditions associated with prolonged QT interval.

• Anticipated or scheduled parathyroidectomy during the study period.

• Anticipated or scheduled kidney transplant during the study period.

• Subject has received a parathyroidectomy within 6 months prior to enrollment.

• Other Medical Conditions:

• Current malignancy or history of other malignancy, except non-melanoma skin cancerswithin the last 5 years.

• Prior/Concomitant Therapy:

• Use of concomitant medications that may prolong the QTc (eg, ondansetron, albuterol,sotalol, amiodarone, erythromycin, or clarithromycin). Refer to CredibleMeds.org forguidance.

• Receipt of cinacalcet therapy within 30 days prior to screening and throughenrollment.

• Receipt of etelcalcetide therapy within 6 months prior to screening and throughenrollment.

• All herbal medicines (eg, St. John's wort), vitamins, and supplements consumed bythe subject within the 30 days prior to enrollment, and continuing use ifapplicable, will be reviewed by the Principal Investigator and the Amgen MedicalMonitor. Written documentation of the review and Amgen acknowledgment is requiredfor subject participation.

• Use of any over-the-counter or prescription medications within the 14 days or 5half-lives (whichever is longer) prior to enrollment that are not establishedtherapies for subjects with renal disease or other conditions secondary to renaldisease will be reviewed by the Principal Investigator and the Amgen MedicalMonitor. Written documentation of the review and Amgen acknowledgment is requiredfor subject participation. Paracetamol for analgesia will be allowed.

• Prior/Concurrent Clinical Study Experience:

• Currently receiving treatment in another investigational device or drug study, orless than 30 days since ending treatment on another investigational device or drugstudy(ies). Other investigational procedures while participating in this study areexcluded.

• Diagnostic Assessments During Screening:

• Subject has significant abnormalities on the most recent central laboratory testduring the screening period prior to enrollment per the Investigator including butnot limited to the following: a. Serum transaminase (alanine aminotransferase [ALT]or serum glutamic pyruvic transaminase [SGPT], aspartate aminotransferase [AST], orserum glutamic oxaloacetic transaminase [SGOT]) greater than 1.5 times the upperlimit of normal (ULN).

• Corrected QT interval greater than 500 ms, using Bazett's formula.

• Corrected QT interval greater than or equal to 450 to less than or equal to 500 ms,using Bazett's formula, unless written permission to enroll is provided by theinvestigator after consultation with a pediatric cardiologist.

• 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.

• Within the 3 Months Prior to Screening:

• New onset or worsening of a pre-existing seizure disorder.

• 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, thenthe subject must have a therapeutic blood level within 1 week of enrollment).

Other Exclusions:

• Female subject is pregnant or breastfeeding or planning to become pregnant orbreastfeed during treatment and for an additional 3 months after the last dose ofetelcalcetide. (Females of childbearing potential should only be included in thestudy after a confirmed menstrual period and a negative highly sensitive serumpregnancy test within 7 days prior to the first dose of investigational product).

• Female subjects of childbearing potential unwilling to use 1 highly effective oracceptable method of effective contraception during treatment and for an additional 3 months after the last dose of investigational product. Refer to Appendix 5 foradditional contraceptive information.

• Female subjects of childbearing potential with a positive pregnancy test assessed atscreening by a serum pregnancy test.

• Subject has known sensitivity to etelcalcetide or excipients to be administeredduring dosing.

• Subject likely to not be available to complete all protocol-required study visits orprocedures, and/or to comply with all required study procedures to the best of thesubject and investigator's knowledge.

• History or evidence of any other clinically significant disorder, condition ordisease (with the exception of those outlined above) or unacceptable physicalfindings, that, in the opinion of the investigator or Amgen physician, if consulted,would pose a risk to subject safety or interfere with the study evaluationprocedures or completion.

• Subject previously has entered this study.

• Anemia, which in the opinion of the investigator makes it not advisable to undergosequential blood draws.

• History of unstable chronic heart failure within the last 1 year prior to screening.