Extension Study of Etelcalcetide in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease (CKD) on Hemodialysis

Study Overview
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Brief Summary
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This study is designed to describe the long-term safety and efficacy of etelcalcetide (AMG 416) for the treatment of SHPT in adults with CKD on hemodialysis.

Official Title
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A Multicenter Single-arm Extension Study to Describe the Long-term Efficacy and 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 understands the study procedures and agrees to participate in the study by giving written informed consent. Subject must complete the treatment and follow-up period, or have been discontinued for rising intact parathyroid hormone (iPTH), from an AMG 416 phase 3 parent study prior to the start of dosing in this study: 20120229 (NCT01785849), 20120230 (NCT01788046), or 20120359 (NCT01932970). Subject agrees to not participate in another study of an investigational agent during the study. Other Inclusion Criteria may apply Exclusion Criteria: Currently receiving treatment in another investigational device or drug study. Currently receiving other investigational procedures while participating in this study. Subject has known sensitivity to any of the products or components to be administered during dosing. Subject has an unstable medical condition based on medical history, physical examination, and routine laboratory tests, or is otherwise unstable in the judgment of the Investigator. Other Exclusion Criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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 at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. | Drug: Etelcalcetide<br>* Administered by bolus injection into the venous line of the dialysis circuit at the end of hemodialysis treatment, and prior to or during rinse-back with each hemodialysis session (ie, 3 times per week).<br>* Other names: AMG 416;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | Treatment-related adverse events are those the investigator indicated as having a reasonable possibility of having been caused by etelcalcetide. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: • fatal • life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • congenital anomaly/birth defect • other medically important serious event. | From first dose until 30 days after last dose; the treatment period was 52 weeks. | 
| Number of Participants With Shift in Laboratory Values From Baseline Grade 0 or 1 to Post-baseline Grade 3 or 4 | Laboratory toxicity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, where Grade 0 represents values in the normal range and grade 4 represents values with life-threatening consequences and urgent intervention indicated. | 52 weeks | 
| Number of Participants Who Developed Anti-etelcalcetide Antibodies | A validated dual flow-cell biosensor immunoassay was used to detect antibodies capable of binding etelcalcetide. The number of participants with a negative or no result at baseline and positive binding antibodies at any time post-baseline is reported. | Baseline, Week 12, Week 24, Week 36, Week 53, the 30-day follow-up visit | 
| Change From Baseline in Blood Pressure | Blood pressure (BP) values were taken post-hemodialysis assessments. | Baseline and Weeks 24 and 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With > 30% Reduction From Baseline in PTH During the Efficacy Assessment Phase | The efficacy assessment phase (EAP) is defined as the last 6 weeks before ending treatment, which was only for participants who completed a minimum of 8 weeks of treatment with etelcalcetide. If multiple assessments were available during the EAP, values were averaged. | Baseline and the efficacy assessment phase, defined as the last 6 weeks prior to ending treatment for participants who completed a minimum of 8 weeks of treatment (weeks 46-52 for participants who completed 52 weeks of treatment) | 
| Percentage of Participants With > 30% Reduction From Baseline in PTH During the EAP12 | The efficacy assessment phase at 12 months (EAP12) was defined as the period from week 46 to 53 (inclusive). If multiple assessments were available during the EAP12, values were averaged. | Baseline and the efficacy assessment phase at month 12 (weeks 46-53) | 
| Percentage of Participants With PTH ≤ 300 pg/mL During the EAP |  | Baseline and the efficacy assessment phase | 
| Percentage of Participants With PTH ≤ 300 pg/mL During the EAP12 |  | Week 46 to 53 | 
| Percent Change From Baseline in Mean PTH During the EAP |  | Baseline and the efficacy assessment phase | 
| Percent Change From Baseline in Mean PTH During the EAP12 |  | Baseline and the efficacy assessment phase at month 12 (weeks 46-53) | 
| Percent Change From Baseline in Mean Corrected Calcium During the EAP |  | Baseline and the efficacy assessment phase | 
| Percent Change From Baseline in Mean Corrected Calcium During the EAP12 |  | Baseline and the efficacy assessment phase at month 12 (weeks 46-53) | 
| Percent Change From Baseline in Mean Corrected Calcium Phosphorus Product During the EAP |  | Baseline and the efficacy assessment phase | 
| Percent Change From Baseline in Mean Corrected Calcium Phosphorus Product During the EAP12 |  | Baseline and the efficacy assessment phase at month 12 (weeks 46-53) | 
| Percent Change From Baseline in Mean Phosphorus During the EAP |  | Baseline and the efficacy assessment phase | 
| Percent Change From Baseline in Mean Phosphorus During the EAP12 |  | Baseline and the efficacy assessment phase at month 12 (weeks 46-53) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Secondary Hyperparathyroidism (SHPT), chronic kidney disease (CKD), hemodialysis, parathyroid hormone (PTH), hypocalcemia, bone and mineral metabolism