A Phase 3 Study of Etelcalcetide in Pediatric Subjects With Secondary Hyperparathyroidism and Chronic Kidney Disease on Hemodialysis
- Conditions
- Health Condition 1: N258- Other disorders resulting from impaired renal tubular function
- Registration Number
- CTRI/2019/05/018959
- Lead Sponsor
- Amgen Technology Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
1. Subjectâ??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.
2. Male or female subjects 28 days to < 18 years of age at the time of enrollment.
3. Targeted Dry weight >= 7 kg during screening week -1.
4. 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 â?? only need to be undergoing hemodialysis at time of screening
5. 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.
6. 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.
7. Dialysate Ca level >= 2.5 mEq/L during screening for at least 4 weeks prior to screening (per Section 7.8.3) and throughout the duration of the study.
8. Subject receiving active vitamin D sterols must have had no more than a maximum prescribed dose change of 50% 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 9. Subject receiving phosphate binders must have had no more than a maximum prescribed dose change of 50% 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.
10. 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.
11. SHPT not due to vitamin D deficiency, per investigator assessment
Disease Related
1. History of congenital long QT syndrome, second or third degree heart block,
ventricular tachyarrhythmiaâ??s or other conditions associated with prolonged QT
interval.
2. Anticipated or scheduled parathyroidectomy during the study period.
3. Anticipated or scheduled kidney transplant during the study period.
4. Subject has received a parathyroidectomy within 6 months prior to
randomization.
Other Medical Conditions
5. History of other malignancy, except non-melanoma skin cancers, cervical or
breast ductal carcinoma in situ within the last 5 years.
Prior/Concomitant Therapy
6. 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.
7. Receipt of cinacalcet therapy within 30 days prior to screening assessments
and through randomization.
8. Receipt of etelcalcetide within 6 months prior to screening assessments and
through randomization.
9. All herbal medicines (eg, St. Johnâ??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.
10. 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
11. 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
12. 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).
13. Corrected QT interval (QTc) > 500 ms, using Bazettâ??s formula.
14. QTc >=450 to <= 500ms using Bazettâ??s formula, unless writted permission to
enroll is provided by the investigator after consultation with a pediatric
cardiologist.
15. 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 pr
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 hemodialysisTimepoint: Achievement of at least a 30% reduction from baseline in mean iPTH during the efficacy assessment phase (EAP)
- Secondary Outcome Measures
Name Time Method 1. To characterize PK of etelcalcetide treatment:Cmax and Cmin <br/ ><br>2. To characterize the safety of etelcalcetide treatment <br/ ><br>3. To characterize change in laboratory markers of CKD following etelcalcetide treatmentTimepoint: Nature, freq.,severity & relationship to treatment of all ADs include those of spcl. interest reported in study. Freq. of hypocalcemia. Occurrence of corrected serum Ca levels Less than (LT.) 8.0mg/dL(2.0mmol/L)for age 2-LT.18 yr and LT. 8.6mg/dL(2.15mmol/L) for 28 days to LT.2 yr in the study. Changes in lab parameters at scheduled visits. Percent change from baseline in predialysis iPTH during the EAP& Percent change in corrected total serum Ca & serum phosphorus from baseline during the EAP