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

Chronic Kidney Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03299244
• Other study ID #: 20150238
• Status: Completed
• Phase: Phase 3
• Start date: May 15, 2018
• Est. completion date: April 8, 2020

Study information

• Verified date: April 2021
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 637
• Est. completion date: April 8, 2020
• Est. primary completion date: April 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Hyperparathyroidism
• Hyperparathyroidism, Secondary
• Kidney Diseases
• Neoplasm Metastasis
• Renal Insufficiency, Chronic
• Secondary Hyperparathyroidism

Intervention

Drug:
• Etelcalcetide
Administered intravenously three times per week.
• Cinacalcet
Cinacalcet administered orally once a day.

Locations

Country	Name	City	State
China	Research Site	Beijing	Beijing
China	Research Site	Changchun	Jilin
China	Research Site	Changchun	Jilin
China	Research Site	Changsha	Hunan
China	Research Site	Changsha	Hunan
China	Research Site	Changzhou	Jiangsu
China	Research Site	Chengdu	Sichuan
China	Research Site	Chengdu	Sichuan
China	Research Site	Dalian	Liaoning
China	Research Site	Dalian	Liaoning
China	Research Site	Dalian	Liaoning
China	Research Site	Guangzhou	Guangdong
China	Research Site	Guangzhou	Guangdong
China	Research Site	Guangzhou	Guangdong
China	Research Site	Guangzhou	Guangdong
China	Research Site	Guangzhou	Guangdong
China	Research Site	Hangzhou	Zhejiang
China	Research Site	Hangzhou	Zhejiang
China	Research Site	Lanzhou	Gansu
China	Research Site	Nanjing	Jiangsu
China	Research Site	Nanjing	Jiangsu
China	Research Site	Nanning	Guangxi
China	Research Site	Nanning	Guangxi
China	Research Site	Qingdao	Shandong
China	Research Site	Shanghai	Shanghai
China	Research Site	Shanghai	Shanghai
China	Research Site	Shanghai	Shanghai
China	Research Site	Shanghai	Shanghai
China	Research Site	Shenyang	Liaoning
China	Research Site	Shenyang	Liaoning
China	Research Site	Shenzhen	Guangdong
China	Research Site	Taiyuan	Shanxi
China	Research Site	Tianjin	Tianjin
China	Research Site	Tianjin	Tianjin
China	Research Site	Urumqi	Xinjiang
China	Research Site	Wuhan	Hubei
China	Research Site	Wuhan	Hubei
China	Research Site	Wuhan	Hubei
China	Research Site	Wuxi	Jiangsu
China	Research Site	Xian	Shaanxi
China	Research Site	Zhanjiang	Guangdong
China	Research Site	Zhengzhou	Henan
China	Research Site	Zhengzhou	Henan
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	Kowloon
Hong Kong	Research Site	New Territories
India	Research Site	Ahmedabad	Gujarat
India	Research Site	Belagavi	Karnataka
India	Research Site	Chandigarh	Punjab
India	Research Site	Chennai	Tamil Nadu
India	Research Site	Dehradun	Uttaranchal
India	Research Site	Kozhikode	Kerala
India	Research Site	Kozhikode	Kerala
India	Research Site	Lucknow	Uttar Pradesh
India	Research Site	Mysuru	Karnataka
India	Research Site	Nadiad	Gujarat
India	Research Site	New Delhi	Delhi
India	Research Site	New Delhi	Delhi
India	Research Site	New Delhi	Delhi
India	Research Site	New Delhi	Delhi
India	Research Site	Wardha
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Gumi-si, Gyeongsangbuk-do
Korea, Republic of	Research Site	Guri-si, Gyeonggi-do
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Malaysia	Research Site	Batu Caves	Selangor (incl. Putrajaya)
Malaysia	Research Site	George Town	Pinang
Malaysia	Research Site	Ipoh	Perak
Malaysia	Research Site	Kuching	Sarawak
Taiwan	Research Site	Changhua
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Keelung
Taiwan	Research Site	New Taipei
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

China,  Hong Kong,  India,  Korea, Republic of,  Malaysia,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Primary	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	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).
Secondary	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)
Secondary	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)
Secondary	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)

External Links

•   AmgenTrials clinical trials website