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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; Secondary Hyperparathyroidism
• Intervention / Treatment: Drug: Cinacalcet; Drug: Etelcalcetide

• Study Type: Interventional
• Enrollment (Actual): 637
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Research Site
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • Research Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Research Site
    • Guangzhou, Guangdong, China, 510120
      • Research Site
    • Guangzhou, Guangdong, China, 510150
      • Research Site
    • Guangzhou, Guangdong, China, 510180
      • Research Site
    • Guangzhou, Guangdong, China, 510630
      • Research Site
    • Shenzhen, Guangdong, China, 518035
      • Research Site
    • Zhanjiang, Guangdong, China, 524001
      • Research Site
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Research Site
    • Nanning, Guangxi, China, 530022
      • Research Site
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Research Site
    • Zhengzhou, Henan, China, 450052
      • Research Site
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Research Site
    • Wuhan, Hubei, China, 430034
      • Research Site
    • Wuhan, Hubei, China, 430060
      • Research Site
  • Hunan
    • Changsha, Hunan, China, 410008
      • Research Site
    • Changsha, Hunan, China, 410011
      • Research Site
  • Jiangsu
    • Changzhou, Jiangsu, China, 213003
      • Research Site
    • Nanjing, Jiangsu, China, 210009
      • Research Site
    • Nanjing, Jiangsu, China, 210029
      • Research Site
    • Wuxi, Jiangsu, China, 214023
      • Research Site
  • Jilin
    • Changchun, Jilin, China, 130021
      • Research Site
    • Changchun, Jilin, China, 130041
      • Research Site
  • Liaoning
    • Dalian, Liaoning, China, 116001
      • Research Site
    • Dalian, Liaoning, China, 116011
      • Research Site
    • Dalian, Liaoning, China, 116027
      • Research Site
    • Shenyang, Liaoning, China, 110004
      • Research Site
    • Shenyang, Liaoning, China, 110022
      • Research Site
  • Shaanxi
    • Xian, Shaanxi, China, 710004
      • Research Site
  • Shandong
    • Qingdao, Shandong, China, 266005
      • Research Site
  • Shanghai
    • Shanghai, Shanghai, China, 200072
      • Research Site
    • Shanghai, Shanghai, China, 200090
      • Research Site
    • Shanghai, Shanghai, China, 200127
      • Research Site
    • Shanghai, Shanghai, China, 200240
      • Research Site
  • Shanxi
    • Taiyuan, Shanxi, China, 030001
      • Research Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Research Site
    • Chengdu, Sichuan, China, 610072
      • Research Site
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Research Site
    • Tianjin, Tianjin, China, 300121
      • Research Site
  • Xinjiang
    • Urumqi, Xinjiang, China, 830054
      • Research Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Research Site
    • Hangzhou, Zhejiang, China, 310009
      • Research Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Research Site
  • Kowloon, Hong Kong
    • Research Site
  • New Territories, Hong Kong
    • Research Site
• India
  • Wardha, India, 442 004
    • Research Site
  • Delhi
    • New Delhi, Delhi, India, 110 017
      • Research Site
    • New Delhi, Delhi, India, 110 025
      • Research Site
    • New Delhi, Delhi, India, 110 060
      • Research Site
    • New Delhi, Delhi, India, 110 070
      • Research Site
  • Gujarat
    • Ahmedabad, Gujarat, India, 380 006
      • Research Site
    • Nadiad, Gujarat, India, 387 001
      • Research Site
  • Karnataka
    • Belagavi, Karnataka, India, 590010
      • Research Site
    • Mysuru, Karnataka, India, 570001
      • Research Site
  • Kerala
    • Kozhikode, Kerala, India, 673 004
      • Research Site
    • Kozhikode, Kerala, India, 673 008
      • Research Site
  • Punjab
    • Chandigarh, Punjab, India, 160 012
      • Research Site
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600 006
      • Research Site
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226 014
      • Research Site
  • Uttaranchal
    • Dehradun, Uttaranchal, India, 248 001
      • Research Site
• Korea, Republic of
  • Busan, Korea, Republic of, 602-715
    • Research Site
  • Busan, Korea, Republic of, 602-739
    • Research Site
  • Daegu, Korea, Republic of, 700-721
    • Research Site
  • Gumi-si, Gyeongsangbuk-do, Korea, Republic of, 730-728
    • Research Site
  • Guri-si, Gyeonggi-do, Korea, Republic of, 471-701
    • Research Site
  • Seoul, Korea, Republic of, 156-707
    • Research Site
  • Seoul, Korea, Republic of, 156-755
    • Research Site
  • Seoul, Korea, Republic of, 130-872
    • Research Site
  • Seoul, Korea, Republic of, 133-817
    • Research Site
  • Seoul, Korea, Republic of, 134-727
    • Research Site
  • Seoul, Korea, Republic of, 135-720
    • Research Site
  • Seoul, Korea, Republic of, 150-950
    • Research Site
• Malaysia
  • Perak
    • Ipoh, Perak, Malaysia, 30450
      • Research Site
  • Pinang
    • George Town, Pinang, Malaysia, 10990
      • Research Site
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Research Site
  • Selangor (incl. Putrajaya)
    • Batu Caves, Selangor (incl. Putrajaya), Malaysia, 68100
      • Research Site
• Taiwan
  • Changhua, Taiwan, 50006
    • Research Site
  • Kaohsiung, Taiwan, 83301
    • Research Site
  • Keelung, Taiwan, 20401
    • Research Site
  • New Taipei, Taiwan, 23561
    • Research Site
  • Taichung, Taiwan, 40705
    • Research Site
  • Taichung, Taiwan, 40201
    • Research Site
  • Tainan, Taiwan, 71004
    • Research Site
  • Tainan, Taiwan, 70403
    • Research Site
  • Taipei, Taiwan, 10002
    • Research Site
  • Taipei, Taiwan, 10449
    • Research Site
  • Taipei, Taiwan, 11101
    • Research Site
  • Taipei, Taiwan, 11031
    • Research Site
  • Taoyuan, Taiwan, 33305
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cinacalcet; 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; Cinacalcet administered orally once a day.; Other Names: Sensipar®; Mimpara®
Experimental: Etelcalcetide; 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; Administered intravenously three times per week.; Other Names: AMG 416; Parsabiv®

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With cCa < 8.3 mg/dL At Any Time During the Study	Corrected calcium was measured by the central laboratory.	From first dose of study drug to end of study; up to 26 weeks + 30 days.
Number of Participants With cCa < 8.0 mg/dL At Any Time During the Study	Corrected calcium was measured by the central laboratory.	From first dose of study drug to end of study; up to 26 weeks + 30 days.
Number of Participants With cCa < 7.5 mg/dL At Any Time During the Study	Corrected calcium was measured by the central laboratory.	From first dose of study drug to end of study; up to 26 weeks + 30 days.
Number of Participants With Treatment-emergent Symptomatic Hypocalcemia During the Study	Common symptoms of hypocalcemia (diminished blood calcium) include paresthesias (fingertips, toes, or perioral), fatigue, muscle cramps, irritability or anxiety, tetany (eg, carpopedal spasm, laryngospasm), Chvostek's sign, seizures, and prolonged QT interval.	From first dose of study drug to 30 days after last dose; up to 26 weeks + 30 days.
Number of Participants Who Developed Antibodies to Etelcalcetide	Developing antibody incidence is defined as participants who were binding antibody positive post-baseline with a negative or no result at baseline.	From first dose of study drug to 30 days after last dose; up to 26 weeks + 30 days.
Number of Participants With Treatment-emergent Adverse Events	An adverse event is defined as any untoward medical occurrence in a clinical study participant, including worsening of a pre-existing medical condition. The event does not necessarily have a causal relationship with study treatment. The investigator assessed whether each adverse event was possibly related to study drug. A serious adverse event is defined as an adverse event that met at least 1 of the following serious criteria: fatal; life threatening; required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event	From first dose of study drug to 30 days after last dose; up to 26 weeks + 30 days.

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2018
• Primary Completion (Actual): April 8, 2020
• Study Completion (Actual): April 8, 2020

Study Registration Dates

• First Submitted: September 15, 2017
• First Submitted That Met QC Criteria: September 27, 2017
• First Posted (Actual): October 3, 2017

Study Record Updates

• Last Update Posted (Actual): April 30, 2021
• Last Update Submitted That Met QC Criteria: April 5, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Parathyroid Diseases; Neoplastic Processes; Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism; Neoplasm Metastasis; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Calcium-Regulating Hormones and Agents; Calcimimetic Agents; Cinacalcet
• Other Study ID Numbers: 20150238

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No