Overview
This is a Phase 3 Study of Etelcalcetide in Pediatric Subjects With Secondary Hyperparathyroidism and Chronic Kidney Disease on Hemodialysis
Description
SHPT is a common and serious co-morbidity that develops relatively early in the course of CKD, worsens with declining kidney function, and is associated with serious complications in children on dialysis. Children on dialysis experience a wide spectrum of bone abnormalities and growth retardation, in addition to increased risk for cardiovascular morbidity and mortality that manifests early in their adulthood. Traditional therapies for SHPT (eg, vitamin D sterols) are widely used in the pediatric dialysis population, and have the potential to aggravate complications of the disease by increasing serum calcium (Ca), serum phosphorus, and serum Ca times serum phosphorus product.
Etelcalcetide has been shown to be safe and efficacious in treating adult CKD patients with SHPT by simultaneously controlling intact parathyroid hormone (iPTH), Ca, and phosphorus and has recently been approved for use in adult patients with SHPT treated with hemodialysis in both the United States and Europe. Although no previous studies have been conducted in pediatric patients with etelcalcetide (one single dose pharmacokinetic [PK] study is currently ongoing),Amgen anticipates minimal to moderate risk with a possibility of direct benefit to the pediatric subjects (age 28 days to 18 years) in this study. The burden of complications of SHPT in the pediatric dialysis population and the limitations of current standard therapy, underscore the need for studies of etelcalcetide in these patients to address this unmet medical need and inform the pediatric nephrology community of the potential use of etelcalcetide in children on hemodialysis with critical safety and efficacy data.
Eligibility
Inclusion criteria
- Age of 28 days or older and less than 18 years
- Dry weight ≥ 7 kg during screening.
- Diagnosed with CKD and SHPT undergoing hemodialysis at the time of screening.
- 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 enrolment.
- 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.
- Dialysate Ca level ≥ 2.5 mEq/L during screening for at least 4 weeks prior to screening and throughout the duration of the study.
- No more than a maximum prescribed dose change of 50% for active vitamin D sterols/phosphate binders/Ca supplements within the 2 weeks prior to screening assessments and remain stable.
- 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 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 randomization.
Other Medical Conditions
- History of other malignancy, except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years. Prior/Concomitant Therapy
- 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.
- Receipt of cinacalcet therapy within 30 days prior to screening assessments and through randomization.
- Receipt of etelcalcetide within 6 months prior to screening assessments and through randomization.
- 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.
- 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 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 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
- 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]) > 2.0 times the upper limit of normal (ULN).
- Corrected QT interval (QTc) > 500 ms, using Bazett's formula.
- 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.
- 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
• New onset or worsening of a pre-existing seizure disorder.
Other Exclusions
- Subjects aged 28 days to 6 months of age who were born prematurely at < 36 weeks
gestational age.
- 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 contraception during treatment and for an additional 3 months
after the last dose of investigational product.
- 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 (eg, 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) 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 has previously entered this study