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

Inclusion Criteria:

• Participant's legally acceptable representative has provided informed consent whenthe participant is legally too young to provide informed consent and the participanthas provided written assent based on local regulations and/or guidelines prior toany trial-specific activities/procedures being initiated.

• Male or female participants greater than or equal to 2 to less than 18 years of ageat the time of enrollment.

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

• Diagnosed with CKD and SHPT undergoing hemodialysis/hemodiafiltration TIW or fourtimes a week (QIW) at the time of screening greater than or equal to 1 month.

• Diagnosis of SHPT with the mean of the 2 consecutive central laboratory iPTH valuesgreater than 300 pg/mL during screening, on separate days and within 2 weeks ofenrollment obtained from the central laboratory during screening.

• Serum corrected Ca value greater than or equal to 9.0 mg/dL obtained from thecentral laboratory during screening.

• Dialysate Ca level greater than or equal to 2.5 mEq/L for at least 1 month prior toscreening and throughout the duration of the trial.

• participant receiving active vitamin D sterols must have had no more than a maximumdose change of 50% within the 2 weeks prior to screening laboratory assessments,remain stable through enrollment, and be expected to maintain stable doses for theduration of the trial, except for adjustments allowed per protocol.

• participant receiving phosphate binders 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 trial, except for adjustments allowed per protocol.

• 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 stablethrough enrollment, and be expected to maintain stable dose for the duration of thetrial, except for adjustments allowed per protocol.

• SHPT not due to vitamin D deficiency, per investigator 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 trial period.

• Anticipated or scheduled kidney transplant during the trial period.

• Participant 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. Certain medications may be allowed based on review by the Medical Monitorand require additional electrocardiogram (ECG) monitoring and potential electrolytemonitoring.

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

• Any previous use of etelcalcetide prior to screening and through enrollment (Original protocol, Amendment 1, and Amendment 2 only).

• Receipt of etelcalcetide therapy within 6 months prior to screening assessments andthrough enrollment (Amendment 3 and later only).

• All herbal medicines (eg, St. John's wort), vitamins, and supplements consumed bythe participant 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 participant 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 participants 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 participant participation. Paracetamol for analgesia will be allowed.

• Prior/Concurrent Clinical Trial Experience:

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

• Diagnostic Assessments During Screening:

• Participant 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.

• Participant has a clinically significant ECG abnormality (eg, unstable arrhythmia)during screening that, in the opinion of the investigator, could pose a risk toparticipant safety or interfere with the trial evaluation.

• Within the 3 Months Prior to Screening:

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

• Participants on anti-convulsant medication must be on a stable and therapeutic dosefor 3 months prior to screening (if blood level monitoring is clinically available,then the participant must have a therapeutic blood level within 1 week ofenrollment).

Other Exclusions:

• Female participant 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 thetrial after a confirmed menstrual period and a negative highly sensitive serumpregnancy test within 7 days prior to the first dose of investigational product).

• Female participants 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.

• Female participants of childbearing potential with a positive pregnancy testassessed at screening by a serum pregnancy test.

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

• Participant likely to not be available to complete all protocol-required trialvisits or procedures, and/or to comply with all required trial procedures to thebest of the participant 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 participant safety or interfere with the trial evaluationprocedures or completion.

• Participant has previously entered this trial or previously received treatment withetelcalcetide (Original protocol, Amendment 1 and Amendment 2 only).

• Participant previously has entered this trial (Amendment 3 and later only).

• 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.