Head-to-Head Study of Etelcalcetide (AMG 416) and Cinacalcet

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

Official Title
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A Multicenter, Multiple-dose, Two-arm, Active-controlled, Double-blind, Double-dummy Study to Compare the Therapeutic Efficacy and Safety of Oral Doses of Cinacalcet HCl With Intravenous Doses of AMG 416 in 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
* Drug: Oral Placebo
* Drug: Intravenous Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible subjects must be receiving adequate thrice weekly maintenance hemodialysis with a dialysate calcium concentration ≥ 2.5 mEq/L for at least 3 months prior to screening laboratory assessments Subjects must have SHPT as defined by one central laboratory screening predialysis serum PTH value > 500 pg/mL, measured on separate days within 2 weeks prior to randomization Subjects must have one serum cCa value ≥ 8.3 mg/dL obtained before dialysis within 2 weeks of the date of randomization Subjects receiving calcium supplements must have no more than a maximum dose change of 50% within 2 weeks before screening laboratory assessments are obtained, and the dose must remain unchanged through randomization Exclusion Criteria: Eligible subjects cannot have received cinacalcet during the 3 months preceding the first screening laboratory assessment Other criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cinacalcet<br>Participants were randomized to receive oral cinacalcet once daily and placebo intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 30 mg daily and could 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 corrected calcium (cCa) ≥ 8.3 mg/dL. | Drug: Cinacalcet<br>* Cinacalcet was administered orally once a day. The starting dose was 30 mg daily, titrated up to 180 mg daily based on serum PTH and corrected calcium levels.<br>* Other names: Sensipar®, Mimpara®;Drug: Intravenous Placebo<br>* Administered intravenously (IV) three times per week.<br>|
| 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 could 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. The starting dose was 5 mg, titrated up to 15 mg based on serum PTH and corrected calcium levels.<br>* Other names: AMG 416;Drug: Oral Placebo<br>* Administered orally once a day.<br>|

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 Parathyroid Hormone During the Efficacy Assessment Phase - Non-inferiority Analysis |  | 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 PTH During the Efficacy Assessment Phase |  | Baseline and the efficacy assessment phase (Weeks 20 to 27, inclusive). | 
| Percentage of Participants With > 30% Reduction From Baseline in Mean PTH During the Efficacy Assessment Phase |  | Baseline and the efficacy assessment phase (Week 20 to Week 27) | 
| Mean Number of Days of Vomiting or Nausea Per Week in the First 8 Weeks | Participants completed the Nausea/Vomiting Symptom Assessment (NVSA) questionnaire daily. This questionnaire asked participants to indicate the severity of nausea on a scale from 0 (no nausea) to 10 (as severe as can be imagined) and if they had vomited in the past 24 hours. A day of vomiting or nausea was defined as those where the severity of nausea score was > 0 or where the episodes of vomiting score was > 0. | First 8 weeks | 
| Percent Change From Baseline in Mean Corrected Calcium During the Efficacy Assessment Phase |  | Baseline and the efficacy assessment phase (weeks 20 - 27) | 
| Percentage of Participants With Mean Predialysis Serum Phosphorus ≤ 4.5 mg/dL During the Efficacy Assessment Phase |  | Efficacy assessment phase (weeks 20 - 27) | 
| Mean Severity of Nausea in the First 8 Weeks | Severity of nausea was assessed using the Nausea and Vomiting Symptom Assessment questionnaire which asked participants to rate the severity of nausea on a scale from 0 (no nausea) to 10 (as severe as can be imagined). For each participant, the mean severity of nausea was calculated by averaging all available daily severities (including zeroes) reported in the first 8 weeks. | First 8 weeks | 
| Mean Number of Episodes of Vomiting Per Week in the First 8 Weeks | The number of vomiting episodes was assessed using the Nausea and Vomiting Symptom Assessment questionnaire which asks participants on a daily basis how many times they vomited in the past 24 hours. The number of episodes in a week is the sum of all reported daily episodes in the week. For participants providing less than 7 days of responses to NVSA questions in any given week, data from that week did not contribute to the analysis. | First 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Secondary Hyperparathyroidism, renal, kidney, kidneys, dialysis, hemodialysis, chronic kidney disease, CKD, SHPT