A Study to Investigate the Influence of PTH-lowering by Etelcalcetide (Parsabiv®) on the Calcification Propensity of Serum in Dialysis Patients

Study Overview
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Brief Summary
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This is a single-center, prospective, dose-escalation, pilot study in 15 end-stage renal disease patients on chronic hemodialysis with secondary hyperparathyroidism.

Detailed Description
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Fifteen prevalent and stable hemodialysis patients with secondary hyperparathyroidism eligible for treatment with calcium receptor sensitizers according to current KDIGO will be included. Study phases will begin and end on the day of the first hemodialysis session of the week. The run-in phase will last 4 weeks. No calcimimetics will be prescribed during the run-in phase. The treatment phase starts with a dose of etelcalcetide is 2.5mg thrice weekly. Etelcalcetide dose will be escalated every 4 weeks in 2.5mg/dialysis session increments to a maximum dose of 15mg thrice weekly. The wash-out Phase starts after completion of the 15mg thrice-weekly phase or in case a pre-specified safety endpoint is reached, etelcalcetide will be discontinued and patients will be followed for additional 8 weeks to study any potential reversibility of PTH lowering on T50 results. For the individual patient, the study duration will be 9 months

Official Title
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A Study to Investigate the Influence of PTH-lowering by Etelcalcetide (Parsabiv®) on the Calcification Propensity of Serum in Dialysis Patients

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Drug: Etelcalcetide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prevalent patients (≥ 3 months on dialysis) treated with thrice weekly hemodialysis (HD) or hemodiafiltration (HDF) Secondary hyperparathyroidism defined as PTH levels > 9x ULN according to current KDIGO guidelines if therapy-naïve, or patients already treated with calcium receptor sensitizers with PTH > 2x ULN Albumin corrected calcium ≥ 2,08 mmol/l Calcium concentrations of dialysate stable for at least 2 weeks prior to screening Exclusion Criteria: Currently receiving treatment in another investigational device or drug study or participation in non-interventional studies Current treatment with etelcalcetide (Parsabiv©) or treatment with etelcalcetide within 3 months prior to study inclusion Patient has known sensitivity to any of the products or components of Parsabiv© Patient has received a parathyroidectomy Parathyroidectomy planned or expected during the study period Elective kidney transplant scheduled during the study period Therapy with bisphosphonates within the past 12 months Therapy with denosumab within the past 6 months Antacids containing aluminum, calcium, magnesium or bicarbonate Patient has a history of symptomatic ventricular arrhythmias or Torsades de Pointes Patient has a history of myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting within the past 6 months prior to screening. Pregnant or nursing (lactating) women

Ages Eligible for Study
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Minimum Age: 18 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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This is a single-center, prospective, dose-escalation, pilot study. Starting dose 2.5 mg thrice weekly dose will be escalated every 4 weeks in 2.5mg/dialysis session increments to a maximum dose of 15mg thrice weekly.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etelcalcetide 2.5 mg<br>Etelcalcetide, starting dose of 2.5mg thrice weekly, dose will be escalated every 4 weeks in 2.5mg/dialysis session increments to a maximum dose of 15mg thrice weekly | Drug: Etelcalcetide<br>* Up-Titration<br>* Other names: Parsabiv;|
| Experimental: Etelcalcetide 5 mg<br>Etelcalcetide, starting dose of 2.5mg thrice weekly, dose will be escalated every 4 weeks in 2.5mg/dialysis session increments to a maximum dose of 15mg thrice weekly | Drug: Etelcalcetide<br>* Up-Titration<br>* Other names: Parsabiv;|
| Experimental: Etelcalcetide 7,5 mg<br>Etelcalcetide, starting dose of 2.5mg thrice weekly, dose will be escalated every 4 weeks in 2.5mg/dialysis session increments to a maximum dose of 15mg thrice weekly | Drug: Etelcalcetide<br>* Up-Titration<br>* Other names: Parsabiv;|
| Experimental: Etelcalcetide 10 mg<br>Etelcalcetide, starting dose of 2.5mg thrice weekly, dose will be escalated every 4 weeks in 2.5mg/dialysis session increments to a maximum dose of 15mg thrice weekly | Drug: Etelcalcetide<br>* Up-Titration<br>* Other names: Parsabiv;|
| Experimental: Etelcalcetide 12,5 mg<br>Etelcalcetide, starting dose of 2.5mg thrice weekly, dose will be escalated every 4 weeks in 2.5mg/dialysis session increments to a maximum dose of 15mg thrice weekly | Drug: Etelcalcetide<br>* Up-Titration<br>* Other names: Parsabiv;|
| Experimental: Etelcalcetide 15 mg<br>Etelcalcetide, starting dose of 2.5mg thrice weekly, dose will be escalated every 4 weeks in 2.5mg/dialysis session increments to a maximum dose of 15mg thrice weekly | Drug: Etelcalcetide<br>* Up-Titration<br>* Other names: Parsabiv;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| T50-Laboratory Test for measuring calcification | The changes in T50 values between the different study phases will be evaluated as the primary outcome. | 32 weeks |