Extension Study of Etelcalcetide for Treatment of Secondary Hyperparathyroidism in Patients With Chronic Kidney Disease on Hemodialysis

Study Overview
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Brief Summary
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This is a multicenter, single-arm, extension study to characterize the long-term safety and tolerability of etelcalcetide in the treatment of Secondary Hyperparathyroidism (SHPT) in adults with Chronic Kidney Disease (CKD) on hemodialysis.

Detailed Description
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This is a multicenter, single-arm, extension study in which adults with secondary hyperparathyroidism currently receiving hemodialysis and previously treated in Amgen studies 20120231 (NCT01785875), 20120334 (NCT01576146), or 20120360 (NCT01896232) will continue to be treated with etelcalcetide until approximately 2.5 years after the first participant was enrolled.

Official Title
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A Multicenter Single-arm Extension Study to Describe the Long-term Safety of AMG 416 in the Treatment of Secondary Hyperparathyroidism in Subjects With Chronic Kidney Disease on Hemodialysis

Conditions
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Hyperparathyroidism, Secondary

Intervention / Treatment
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* Drug: Etelcalcetide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has provided informed consent prior to initiation of any study-specific activities/procedures Subject has completed treatment in Study 20120231 (also known as KAI-4169-008) or Study 20120360, or has participated in Study 20120334 (also known as KAI-4169-005-01) Female subjects who are: post-menopausal (post-menopausal is defined as no menses for the previous 1 year and over the age of 50 years), surgically sterilized, have a medical condition that prevents pregnancy, remain abstinent, or are willing to use an acceptable method of effective contraception during the study and for 3 months after the last dose. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 2 weeks prior to the first dose of AMG 416 in the current study Subject must be receiving hemodialysis 3 or 4 times weekly for at least 3 months Exclusion Criteria: Currently receiving treatment in another investigational device or drug study (other than in one of the designated parent studies) Subject has known sensitivity to any of the products or components to be administered during dosing Subject has been prescribed cinacalcet by the primary nephrologist between the conclusion of the parent study and the start of dosing with AMG 416 in the current study Subject is receiving dialysis prescription dialysate calcium concentration < 2.25 mEq/L Subject is pregnant or nursing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 110 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etelcalcetide<br>Participants received etelcalcetide three times a week (TIW) by bolus injection at the end of hemodialysis. The minimum etelcalcetide dose in this study was 2.5 mg and the maximum dose was 15 mg. Etelcalcetide dose was titrated to maintain parathyroid hormone levels within 2x to 9x the upper limit of normal based on the reference range of the assay used at the individual study center. | Drug: Etelcalcetide<br>* Etelcalcetide was supplied as a sterile, preservative-free, ready-to-administer aqueous solution.<br>* Other names: Parasabiv;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | A serious adverse event is an AE that met at least 1 of the following criteria: fatal life threatening required in-patient hospitalization or prolongation of existing hospitalization resulted in persistent or significant disability/incapacity congenital anomaly/birth defect other medically important serious event. The relationship of each AE to study treatment was assessed by the investigator. The following AE grading scale was used: Mild: Transient or mild discomfort; no limitation in activity; no medical intervention/therapy required Moderate: Mild to moderate limitation in activity-some assistance may be needed; no or minimal medical intervention/therapy required Severe: Marked limitation in activity, some assistance usually required; medical intervention/therapy required, hospitalization possible Life-threatening: Extreme limitation in activity, significant assistance required, significant medical intervention/therapy required, hospitalization probable. | From the date of first dose of etelcalcetide (in the current study) and up to 30 days after the last dose; median duration of treatment was 563 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Parathyroid Hormone Levels Between Two to Nine-times the Upper Limit of Normal | The percentage of participants who maintained plasma parathyroid hormone (PTH) levels within the Kidney Disease Improving Global Outcomes (KDIGO) recommended range of not less than 2x the upper limit of normal (ULN) and not greater than 9x the ULN at months 6, 12, and 18, with the ULN based on the reference range of the assay used at the individual clinical site. | Months 6, 12, and 18 | 
| Percentage of Participants With Serum Phosphorus ≤ the ULN | Percentage of participants with serum phosphorus less than or equal to the upper limit of normal for the assay used. | Months 6, 12, and 18 | 
| Percentage of Participants With Serum Corrected Calcium < 7.5 mg/dL | The percentage of participants with serum corrected calcium (cCa) reported for cumulative time intervals from day 1 through months 6, 12, and 18, using the participant's lowest recorded corrected calcium value during the time interval. If serum albumin was less than 4.0 g/dL, serum calcium was corrected according to the following formula: cCa (mg/dL) = total calcium (mg/dL) + (4 - albumin [g/dL])*0.8. If serum albumin was > 4.0 g/dL no correction was made. | From day 1 to months 6, 12, and 18 | 
| Number of Participants With Shifts From Baseline Grade 0 or 1 to Postbaseline Grade 3 or 4 for Laboratory Parameters | The Common Terminology Criteria for Adverse Events (CTCAE) grades for laboratory parameter values were defined based on the upper/lower limit of normal from the local laboratories contracted by the study centers. | Baseline to end of treatment; median duration of treatment was 563 days. | 
| Number of Participants Who Developed Positive Binding Anti-Etelcalcetide Antibodies | The number of participants who were binding antibody positive post-baseline with a negative or no result at baseline (where baseline for participants previously treated with etelcalcetide is Day 1 of the first study in which they were exposed to etelcalcetide and for participants previously treated with cinacalcet is the ending time point for study 20120360). | Baseline and every 6 months (up to 24 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Secondary Hyperparathyroidism (SHPT), chrominc kidney disease (CKD), hemodialysis