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

Amgen

Status and phase

Enrolling

Phase 3

Conditions

Secondary Hyperparathyroidism

Treatments

Drug: Etelcalcetide

Study type

Interventional

Funder types

Industry

Identifiers

NCT03969329

20170724

Details and patient eligibility

About

Assess the efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of etelcalcetide in the treatment of secondary hyperparathyroidism (SHPT) in pediatric subjects between ≥ 2 to < 18 years of age, with chronic kidney disease (CKD) on hemodialysis

Enrollment

24 estimated patients

Sex

All

Ages

2 to 17 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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.
Male or female subjects greater than or equal to 2 to less than 18 years of age at the 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 of screening greater than or equal to 1 month.
Diagnosis of secondary hyperparathyroidism (SHPT) with the mean of the 2 consecutive central laboratory intact parathyroid hormone (iPTH) values greater than 300 pg/mL during screening, on separate days and within 2 weeks of enrollment obtained from the central laboratory during screening.
Serum corrected calcium (cCa) value greater than or equal to 9.0 mg/dL obtained from the central laboratory during screening.
Dialysate calcium (Ca) level greater than or equal to 2.5 mEq/L for at least 1 month prior to screening and throughout the duration of the study.
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.
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.
Subject receiving calcium (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.
Secondary hyperparathyroidism (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 dysrhythmias Torsades 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 cancers within 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 for guidance.
Receipt of cinacalcet therapy within 30 days prior to screening and through enrollment.
Receipt of etelcalcetide therapy within 6 months prior to screening and through enrollment.
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.
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 for analgesia will be allowed.
Prior/Concurrent Clinical Study Experience:
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.
Diagnostic Assessments During Screening:
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]) greater than 1.5 times the upper limit 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 the investigator 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, then the 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 or breastfeed during treatment and for an additional 3 months 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 highly sensitive serum pregnancy test within 7 days prior to the first dose of investigational product).
Female subjects of childbearing potential unwilling to use 1 highly effective or acceptable method of effective contraception during treatment and for an additional 3 months after the last dose of investigational product. Refer to Appendix 5 for additional contraceptive information.
Female subjects of childbearing potential with a positive pregnancy test assessed at screening by a serum pregnancy test.
Subject has known sensitivity to etelcalcetide or excipients to be administered during dosing.
Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge.
History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) or unacceptable physical findings, 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.
Subject previously has entered this study or previously received treatment with etelcalcetide.
Anemia, which in the opinion of the investigator makes it not advisable to undergo sequential blood draws.
History of unstable chronic heart failure within the last 1 year prior to screening.