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

NCT03299244 | Completed Phase 3 Results

• 1 other identifier: 20150238
• Study Type: interventional
• Target: 637
• Locations: 6 countries
• Sites: 90

Brief Summary

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.

Conditions

Secondary Hyperparathyroidism; Chronic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Percentage of Participants With > 50% Reduction From Baseline in Mean Predialysis iPTH 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 Predialysis iPTH During the Efficacy Assessment Phase - Superiority Analysis

  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

  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

  Efficacy assessment phase (weeks 20 - 27, inclusive)

Other Outcomes (6)

• Number of Participants With cCa < 8.3 mg/dL At Any Time During the Study

  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

  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

  From first dose of study drug to end of study; up to 26 weeks + 30 days.

Study Arms (2)

Cinacalcet

ACTIVE COMPARATOR

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

Etelcalcetide

EXPERIMENTAL

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

Interventions

Etelcalcetide DRUG

Administered intravenously three times per week.

Also known as: AMG 416, Parsabiv®

Etelcalcetide

Cinacalcet DRUG

Cinacalcet administered orally once a day.

Also known as: Sensipar®, Mimpara®

Cinacalcet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (90)

Research Site

Beijing, Beijing Municipality, 100034, China

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Lanzhou, Gansu, 730000, China

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Guangzhou, Guangdong, 510080, China

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Guangzhou, Guangdong, 510120, China

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Guangzhou, Guangdong, 510150, China

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Guangzhou, Guangdong, 510180, China

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Guangzhou, Guangdong, 510630, China

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Shenzhen, Guangdong, 518035, China

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Zhanjiang, Guangdong, 524001, China

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Nanning, Guangxi, 530021, China

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Nanning, Guangxi, 530022, China

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Zhengzhou, Henan, 450003, China

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Zhengzhou, Henan, 450052, China

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Wuhan, Hubei, 430030, China

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Wuhan, Hubei, 430034, China

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Wuhan, Hubei, 430060, China

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Changsha, Hunan, 410008, China

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Changsha, Hunan, 410011, China

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Changzhou, Jiangsu, 213003, China

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Nanjing, Jiangsu, 210009, China

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Nanjing, Jiangsu, 210029, China

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Wuxi, Jiangsu, 214023, China

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Changchun, Jilin, 130021, China

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Changchun, Jilin, 130041, China

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Dalian, Liaoning, 116001, China

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Dalian, Liaoning, 116011, China

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Dalian, Liaoning, 116027, China

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Shenyang, Liaoning, 110004, China

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Shenyang, Liaoning, 110022, China

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Xi'an, Shaanxi, 710004, China

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Qingdao, Shandong, 266005, China

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Shanghai, Shanghai Municipality, 200072, China

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Shanghai, Shanghai Municipality, 200090, China

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Shanghai, Shanghai Municipality, 200127, China

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Shanghai, Shanghai Municipality, 200240, China

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Taiyuan, Shanxi, 030001, China

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Chengdu, Sichuan, 610041, China

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Chengdu, Sichuan, 610072, China

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Tianjin, Tianjin Municipality, 300052, China

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Tianjin, Tianjin Municipality, 300121, China

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Ürümqi, Xinjiang, 830054, China

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Hangzhou, Zhejiang, 310003, China

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Hangzhou, Zhejiang, 310009, China

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Hong Kong, Hong Kong

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Kowloon, Hong Kong

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New Territories, Hong Kong

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Ahmedabad, Gujarat, 380 006, India

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Nadiād, Gujarat, 387 001, India

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Belagavi, Karnataka, 590010, India

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Mysuru, Karnataka, 570001, India

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Kozhikode, Kerala, 673 004, India

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Kozhikode, Kerala, 673 008, India

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New Delhi, National Capital Territory of Delhi, 110 017, India

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New Delhi, National Capital Territory of Delhi, 110 025, India

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New Delhi, National Capital Territory of Delhi, 110 060, India

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New Delhi, National Capital Territory of Delhi, 110 070, India

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Chandigarh, Punjab, 160 012, India

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Chennai, Tamil Nadu, 600 006, India

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Lucknow, Uttar Pradesh, 226 014, India

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Dehradun, Uttarakhand, 248 001, India

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Wardha, 442 004, India

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Ipoh, Perak, 30450, Malaysia

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George Town, Pulau Pinang, 10990, Malaysia

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Kuching, Sarawak, 93586, Malaysia

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Batu Caves, Selangor (incl. Putrajaya), 68100, Malaysia

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Busan, 602-715, South Korea

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Busan, 602-739, South Korea

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Daegu, 700-721, South Korea

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Gumi-si, Gyeongsangbuk-do, 730-728, South Korea

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Guri-si, Gyeonggi-do, 471-701, South Korea

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Seoul, 130-872, South Korea

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Seoul, 133-817, South Korea

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Seoul, 134-727, South Korea

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Seoul, 135-720, South Korea

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Seoul, 150-950, South Korea

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Seoul, 156-707, South Korea

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Seoul, 156-755, South Korea

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Changhua, 50006, Taiwan

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Kaohsiung City, 83301, Taiwan

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Keelung, 20401, Taiwan

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New Taipei City, 23561, Taiwan

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Taichung, 40201, Taiwan

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Taichung, 40705, Taiwan

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Tainan, 70403, Taiwan

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Tainan, 71004, Taiwan

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Taipei, 10002, Taiwan

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Taipei, 10449, Taiwan

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Taipei, 11031, Taiwan

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Taipei, 11101, Taiwan

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Taoyuan District, 33305, Taiwan

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Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hyperparathyroidism, Secondary; Renal Insufficiency, Chronic

Interventions

etelcalcetide hydrochloride; Cinacalcet

Condition Hierarchy (Ancestors)

Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will be randomized by Interactive Voice Response (IVR)/Interactive Web Response (IWR) in a 1:1 ratio to either three times per week (TIW) intravenous (IV) etelcalcetide (and daily oral placebo tablets) or daily oral cinacalcet tablets (and TIW IV placebo) in a double-blind, double-dummy manner. Treatment groups will be blinded to the investigator, participants, and the Amgen study team.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2017
• First Posted: October 3, 2017
• Study Start: May 15, 2018
• Primary Completion: April 8, 2020
• Study Completion: April 8, 2020
• Last Updated: April 30, 2021
• Results First Posted: April 30, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

IN (15); HK (3); KR (12); MY (4); TW (13); CN (43)