Head-to-Head Study of Etelcalcetide and Cinacalcet in Asian Hemodialysis Patients With Secondary Hyperparathyroidism (SHPT)

Study Overview
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Brief Summary
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The primary objective is to demonstrate that treatment with etelcalcetide (AMG 416) is not inferior to treatment with cinacalcet for lowering serum intact parathyroid hormone (PTH) levels by > 30% from baseline among participants with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT) who require management with hemodialysis.

Official Title
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A Multicenter, Multiple-dose, Active-controlled, Double-blind, Double-dummy Study to Compare the Therapeutic Efficacy and Safety of Oral Doses of Cinacalcet Hydrochloride With Intravenous Doses of Etelcalcetide (AMG 416) in Asian Hemodialysis Subjects With Secondary Hyperparathyroidism

Conditions
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Secondary Hyperparathyroidism, Chronic Kidney Disease

Intervention / Treatment
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* Drug: Etelcalcetide
* Drug: Cinacalcet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has provided informed consent prior to performing any study-related activities/procedures. Male or female subjects ≥ 18 years of age or older at the time of signing informed consent. Subject must be receiving maintenance hemodialysis 3 times weekly for at least 3 months, with adequate hemodialysis based on a delivered measure of dialysis adequacy (Kt/V) ≥ 1.2 or urea reduction ratio ≥ 65% within 4 weeks prior to screening laboratory assessments. The Kt/V formula used for a subject must be the formula used during routine care prior to screening. Dialysate calcium concentration must be ≥ 2.5 mEq/L (1.25 mmol/L) and stable for at least 4 weeks prior to screening laboratory assessments, and must remain ≥ 2.5 mEq/L (1.25 mmol/L) for the duration of the study. Subject must have SHPT as defined by one central laboratory screening predialysis serum PTH value > 500 pg/mL, within 2 weeks prior to randomization. Subject currently receiving vitamin D sterols must have had no more than a maximum dose change of 50% within the 4 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 or for safety reasons. Subject must have 1 screening predialysis serum cCa laboratory value ≥ 8.3 mg/dL measured within 2 weeks prior to randomization. A subject receiving calcium supplements must have had no more than a maximum dose change of 50% within 2 weeks prior to screening laboratory assessments and remain stable through randomization. A subject receiving phosphate binders must have had no more than a maximum dose change of 50% 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 or for safety reasons. Exclusion Criteria: Currently receiving treatment in another investigational device or drug study, or ≤ 30 days since ending treatment on another investigational device or drug study(s). Other investigational procedures while participating in this study are excluded. Subject has received etelcalcetide in a prior clinical trial of etelcalcetide. Subject has received cinacalcet during the 3 months prior to the first screening laboratory assessments. Subject has known sensitivity to any of the products or components of either cinacalcet or etelcalcetide to be administered during dosing. Subject has previously been randomized in this study. Anticipated or scheduled parathyroidectomy during the study period. Subject has received a parathyroidectomy within 6 months prior to dosing. Anticipated or scheduled kidney transplant during the study period. 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. Malignancy within the last 5 years of screening (except non-melanoma skin cancers or cervical carcinoma in situ). Grapefruit juice is prohibited. Subject is pregnant or nursing, or planning to become pregnant or nurse during treatment or within 3 months after the last dose of etelcalcetide or 30 days after the last dose of cinacalcet Female subject of childbearing potential who is unwilling to use an acceptable method of effective contraception during treatment with investigational product (IP) through 3 months after the last dose of IP. Subject has a history of symptomatic ventricular dysrhythmias or Torsades de Pointes. Subject has a history of myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting within the past 6 months prior to screening. Subject has clinically significant abnormalities on prestudy clinical examination or abnormalities on the most recent central laboratory tests during the screening period prior to randomization according to the Investigator including but not limited to the following: serum albumin < 3.0 g/dL serum magnesium < 1.5 mg/dL serum transaminase (alanine transaminase [ALT] or serum glutamic pyruvic transaminase [SGPT], aspartate aminotransferase [AST] or serum glutamic oxaloacetic transaminase [SGOT]) > 3 times the upper limit of normal (ULN) at screening. Subject likely not available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and Investigator's knowledge. History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the Investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cinacalcet<br>Participants were randomized to receive oral cinacalcet once daily and placebo intravenous (IV) bolus injection at the end of each hemodialysis session three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 25 mg daily and the dose may have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum parathyroid hormone (PTH) ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining corrected calcium (cCa) ≥ 8.3 mg/dL. | Drug: Cinacalcet<br>* Cinacalcet administered orally once a day.<br>* Other names: Mimpara®;|
| Experimental: Etelcalcetide<br>Participants were randomized to receive etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and the dose may have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL. | Drug: Etelcalcetide<br>* Administered intravenously three times per week.<br>* Other names: Parsabiv®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With > 30% Reduction From Baseline in Mean Predialysis Intact Parathyroid Hormone During the Efficacy Assessment Phase - Non-inferiority Analysis | Predialysis intact parathyroid hormone (iPTH) levels were measured by a central laboratory. | Baseline and the efficacy assessment phase (EAP; defined as weeks 20 to 27, inclusive). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With > 50% Reduction From Baseline in Mean Predialysis iPTH During the Efficacy Assessment Phase | Predialysis intact parathyroid hormone levels were measured by a central laboratory. | Baseline and the efficacy assessment phase (weeks 20 to 27, inclusive). | 
| Percentage of Participants With > 30% Reduction From Baseline in Mean Predialysis iPTH During the Efficacy Assessment Phase - Superiority Analysis | Predialysis intact parathyroid hormone levels were measured by a central laboratory. | Baseline and the efficacy assessment phase (weeks 20 to 27, inclusive) | 
| Percent Change From Baseline in Mean Predialysis Corrected Calcium During the Efficacy Assessment Phase | Predialysis corrected calcium was measured by a central laboratory. | Baseline and the efficacy assessment phase (weeks 20 - 27, inclusive) | 
| Percentage of Participants With Mean Predialysis Serum Phosphorus ≤ 4.5 mg/dL During the Efficacy Assessment Phase | Predialysis serum phosphorus was measured by a central laboratory. | Efficacy assessment phase (weeks 20 - 27, inclusive) |