Safety, Tolerability and Efficacy of Etelcalcetide in Hemodialysis Patients With Secondary Hyperparathyroidism

Study Overview
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Brief Summary
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The purpose of this study is to characterize the safety and tolerability and efficacy of multiple ascending doses of etelcalcetide in hemodialysis patients for the treatment of secondary hyperparathyroidism (HPT).

Official Title
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A Double-Blind, Randomized, Placebo-Controlled Multiple Ascending Dose Study to Assess the Safety, Tolerability and Efficacy of KAI-4169 in Hemodialysis Subjects With Secondary Hyperparathyroidism

Conditions
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Secondary Hyperparathyroidism

Intervention / Treatment
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* Drug: Etelcalcetide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject provides written informed consent. Intact parathyroid hormone (PTH) at least 350 pg/mL. Corrected calcium at least 9.0 mg/dL. Hemoglobin at least 9.0 g/dL. Adequate hemodialysis three times per week. Excepting chronic renal failure, subject is judged to be in stable medical condition based on medical history, physical examination, and routine laboratory tests. Exclusion Criteria: History or symptomatic ventricular dysrhythmias. History of angina pectoris or congestive heart failure History of myocardial infarction, coronary angioplasty, or coronary artery bypass grafting within the past 6 months. History of or treatment for seizure disorder. Recent (3 months) parathyroidectomy. Serum transaminases (alanine aminotransferase, aspartate aminotransferase) greater than two times the upper limit of normal at screening.

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: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etelcalcetide<br>Participants received etelcalcetide administered by intravenous injection at the end of each hemodialysis session three times a week (TIW). The starting dose level was 5 mg; dose escalation was to proceed to 10 and 20 mg pending safety review of the prior cohort. | Drug: Etelcalcetide<br>* Administered intravenously (IV) at the end of hemodialysis<br>* Other names: Parsabiv™;|
| Placebo Comparator: Placebo<br>Participants received placebo administered by intravenous injection at the end of each hemodialysis session three times a week (TIW). | Drug: Placebo<br>* Administered intravenously at the end of hemodialysis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Mean Pre-hemodialysis Parathyroid Hormone (PTH) During the Efficacy Assessment Phase | Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period. | Baseline and the efficacy assessment phase (EAP; defined as the period between 3 days before and 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ≥ 30% Reduction From Baseline in Mean Parathyroid Hormone During the Efficacy Assessment Phase | Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period. | Baseline and the efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3) | 
| Percentage of Participants With Mean Parathyroid Hormone ≤ 300 pg/mL During the Efficacy Assessment Phase | The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period. | Efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3) | 
| Percent Change From Baseline in Mean Corrected Calcium (cCa) During the Efficacy Assessment Phase | Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period. | Baseline and the efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3) | 
| Percent Change From Baseline in Mean Phosphorus (P) During the Efficacy Assessment Phase | Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period. | Baseline and the efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3) | 
| Percent Change From Baseline in Corrected Calcium Phosphorus Product (cCa x P) During the Efficacy Assessment Phase | Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period. | Baseline and the efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3) | 
| Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase |  | Efficacy assessment phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinical Trial, Phase 2, Renal Dialysis, Secondary Hyperparathyroidism, Parathyroid hormone