Clinical trial NCT03299244: Head-to-Head Study of Etelcalcetide and Cinacalcet in Asian Hemodialysis Patients With Secondary Hyperparathyroidism (SHPT)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Secondary Hyperparathyroidism
Chronic Kidney Disease
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2017-10-03
Enrollment: 637
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With > 30% Reduction From Baseline in Mean Predialysis Intact Parathyroid Hormone During the Efficacy Assessment Phase - Non-inferiority Analysis
timeFrame: Baseline and the efficacy assessment phase (EAP; defined as weeks 20 to 27, inclusive).
Secondary outcomes:
measure: Percentage of Participants With > 50% Reduction From Baseline in Mean Predialysis iPTH During the Efficacy Assessment Phase
timeFrame: Baseline and the efficacy assessment phase (weeks 20 to 27, inclusive).
measure: Percentage of Participants With > 30% Reduction From Baseline in Mean Predialysis iPTH During the Efficacy Assessment Phase - Superiority Analysis
timeFrame: Baseline and the efficacy assessment phase (weeks 20 to 27, inclusive)
measure: Percent Change From Baseline in Mean Predialysis Corrected Calcium During the Efficacy Assessment Phase
timeFrame: Baseline and the efficacy assessment phase (weeks 20 - 27, inclusive)
measure: Percentage of Participants With Mean Predialysis Serum Phosphorus ≤ 4.5 mg/dL During the Efficacy Assessment Phase
timeFrame: Efficacy assessment phase (weeks 20 - 27, inclusive)
Other outcomes:
measure: Number of Participants With cCa < 8.3 mg/dL At Any Time During the Study
timeFrame: From first dose of study drug to end of study; up to 26 weeks + 30 days.
measure: Number of Participants With cCa < 8.0 mg/dL At Any Time During the Study
timeFrame: From first dose of study drug to end of study; up to 26 weeks + 30 days.
measure: Number of Participants With cCa < 7.5 mg/dL At Any Time During the Study
timeFrame: From first dose of study drug to end of study; up to 26 weeks + 30 days.
measure: Number of Participants With Treatment-emergent Symptomatic Hypocalcemia During the Study
timeFrame: From first dose of study drug to 30 days after last dose; up to 26 weeks + 30 days.
measure: Number of Participants Who Developed Antibodies to Etelcalcetide
timeFrame: From first dose of study drug to 30 days after last dose; up to 26 weeks + 30 days.
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: From first dose of study drug to 30 days after last dose; up to 26 weeks + 30 days.
Locations:
city: Beijing
country: China
facility: Research Site
state: Beijing
city: Lanzhou
country: China
facility: Research Site
state: Gansu
city: Guangzhou
country: China
facility: Research Site
state: Guangdong
city: Guangzhou
country: China
facility: Research Site
state: Guangdong
city: Guangzhou
country: China
facility: Research Site
state: Guangdong
city: Guangzhou
country: China
facility: Research Site
state: Guangdong
city: Guangzhou
country: China
facility: Research Site
state: Guangdong
city: Shenzhen
country: China
facility: Research Site
state: Guangdong
city: Zhanjiang
country: China
facility: Research Site
state: Guangdong
city: Nanning
country: China
facility: Research Site
state: Guangxi
city: Nanning
country: China
facility: Research Site
state: Guangxi
city: Zhengzhou
country: China
facility: Research Site
state: Henan
city: Zhengzhou
country: China
facility: Research Site
state: Henan
city: Wuhan
country: China
facility: Research Site
state: Hubei
city: Wuhan
country: China
facility: Research Site
state: Hubei
city: Wuhan
country: China
facility: Research Site
state: Hubei
city: Changsha
country: China
facility: Research Site
state: Hunan
city: Changsha
country: China
facility: Research Site
state: Hunan
city: Changzhou
country: China
facility: Research Site
state: Jiangsu
city: Nanjing
country: China
facility: Research Site
state: Jiangsu
city: Nanjing
country: China
facility: Research Site
state: Jiangsu
city: Wuxi
country: China
facility: Research Site
state: Jiangsu
city: Changchun
country: China
facility: Research Site
state: Jilin
city: Changchun
country: China
facility: Research Site
state: Jilin
city: Dalian
country: China
facility: Research Site
state: Liaoning
city: Dalian
country: China
facility: Research Site
state: Liaoning
city: Dalian
country: China
facility: Research Site
state: Liaoning
city: Shenyang
country: China
facility: Research Site
state: Liaoning
city: Shenyang
country: China
facility: Research Site
state: Liaoning
city: Xian
country: China
facility: Research Site
state: Shaanxi
city: Qingdao
country: China
facility: Research Site
state: Shandong
city: Shanghai
country: China
facility: Research Site
state: Shanghai
city: Shanghai
country: China
facility: Research Site
state: Shanghai
city: Shanghai
country: China
facility: Research Site
state: Shanghai
city: Shanghai
country: China
facility: Research Site
state: Shanghai
city: Taiyuan
country: China
facility: Research Site
state: Shanxi
city: Chengdu
country: China
facility: Research Site
state: Sichuan
city: Chengdu
country: China
facility: Research Site
state: Sichuan
city: Tianjin
country: China
facility: Research Site
state: Tianjin
city: Tianjin
country: China
facility: Research Site
state: Tianjin
city: Urumqi
country: China
facility: Research Site
state: Xinjiang
city: Hangzhou
country: China
facility: Research Site
state: Zhejiang
city: Hangzhou
country: China
facility: Research Site
state: Zhejiang
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Kowloon
country: Hong Kong
facility: Research Site
city: New Territories
country: Hong Kong
facility: Research Site
city: New Delhi
country: India
facility: Research Site
state: Delhi
city: New Delhi
country: India
facility: Research Site
state: Delhi
city: New Delhi
country: India
facility: Research Site
state: Delhi
city: New Delhi
country: India
facility: Research Site
state: Delhi
city: Ahmedabad
country: India
facility: Research Site
state: Gujarat
city: Nadiad
country: India
facility: Research Site
state: Gujarat
city: Belagavi
country: India
facility: Research Site
state: Karnataka
city: Mysuru
country: India
facility: Research Site
state: Karnataka
city: Kozhikode
country: India
facility: Research Site
state: Kerala
city: Kozhikode
country: India
facility: Research Site
state: Kerala
city: Chandigarh
country: India
facility: Research Site
state: Punjab
city: Chennai
country: India
facility: Research Site
state: Tamil Nadu
city: Lucknow
country: India
facility: Research Site
state: Uttar Pradesh
city: Dehradun
country: India
facility: Research Site
state: Uttaranchal
city: Wardha
country: India
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Gumi-si, Gyeongsangbuk-do
country: Korea, Republic of
facility: Research Site
city: Guri-si, Gyeonggi-do
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Ipoh
country: Malaysia
facility: Research Site
state: Perak
city: George Town
country: Malaysia
facility: Research Site
state: Pinang
city: Kuching
country: Malaysia
facility: Research Site
state: Sarawak
city: Batu Caves
country: Malaysia
facility: Research Site
state: Selangor (incl. Putrajaya)
city: Changhua
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Keelung
country: Taiwan
facility: Research Site
city: New Taipei
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: