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

• Etelcalcetide (Drug), also known as AMG 416, Parsabiv®: Administered intravenously three times per week.
• Cinacalcet (Drug), also known as Sensipar®, Mimpara®: Cinacalcet administered orally once a day.

Primary outcomes

• Percentage of Participants With > 30% Reduction From Baseline in Mean Predialysis Intact Parathyroid Hormone During the Efficacy Assessment Phase - Non-inferiority Analysis [Baseline and the efficacy assessment phase (EAP; defined as weeks 20 to 27, inclusive).]: Predialysis intact parathyroid hormone (iPTH) levels were measured by a central laboratory.

Secondary outcomes

• 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).]: Predialysis intact parathyroid hormone levels were measured by a central laboratory.
• 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)]: Predialysis intact parathyroid hormone levels were measured by a central laboratory.
• Percent Change From Baseline in Mean Predialysis Corrected Calcium During the Efficacy Assessment Phase [Baseline and the efficacy assessment phase (weeks 20 - 27, inclusive)]: Predialysis corrected calcium was measured by a central laboratory.
• Percentage of Participants With Mean Predialysis Serum Phosphorus ≤ 4.5 mg/dL During the Efficacy Assessment Phase [Efficacy assessment phase (weeks 20 - 27, inclusive)]: Predialysis serum phosphorus was measured by a central laboratory.

Other outcomes

• 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.]: Corrected calcium was measured by the central laboratory.
• 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.]: Corrected calcium was measured by the central laboratory.
• 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.]: Corrected calcium was measured by the central laboratory.
• Number of Participants With Treatment-emergent Symptomatic Hypocalcemia During the Study [From first dose of study drug to 30 days after last dose; up to 26 weeks + 30 days.]: 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.
• Number of Participants Who Developed Antibodies to Etelcalcetide [From first dose of study drug to 30 days after last dose; up to 26 weeks + 30 days.]: Developing antibody incidence is defined as participants who were binding antibody positive post-baseline with a negative or no result at baseline.
• Number of Participants With Treatment-emergent Adverse Events [From first dose of study drug to 30 days after last dose; up to 26 weeks + 30 days.]: 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

Sex: All, ages: 18 Years to any

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.

Participant flow

Outcome results

• Percentage of Participants With > 30% Reduction From Baseline in Mean Predialysis Intact Parathyroid Hormone During the Efficacy Assessment Phase - Non-inferiority Analysis (Primary), Number, percentage of participants: Cinacalcet 66.2; Etelcalcetide 71.9
• Percentage of Participants With > 50% Reduction From Baseline in Mean Predialysis iPTH During the Efficacy Assessment Phase (Secondary), Number, percentage of participants: Cinacalcet 41.6; Etelcalcetide 59.1 (p <0.001)
• Percentage of Participants With > 30% Reduction From Baseline in Mean Predialysis iPTH During the Efficacy Assessment Phase - Superiority Analysis (Secondary), Number, percentage of participants: Cinacalcet 58.0; Etelcalcetide 66.3 (p 0.033)
• Percent Change From Baseline in Mean Predialysis Corrected Calcium During the Efficacy Assessment Phase (Secondary), Mean, percent change: Cinacalcet -8.00 +/- 0.50; Etelcalcetide -10.69 +/- 0.53 (p <0.001)
• Percentage of Participants With Mean Predialysis Serum Phosphorus ≤ 4.5 mg/dL During the Efficacy Assessment Phase (Secondary), Number, percentage of participants: Cinacalcet 26.2; Etelcalcetide 29.1 (p 0.41)
• Number of Participants With cCa < 8.3 mg/dL At Any Time During the Study (Other pre specified), Count of participants, Participants: Cinacalcet 245; Etelcalcetide 273
• Number of Participants With cCa < 8.0 mg/dL At Any Time During the Study (Other pre specified), Count of participants, Participants: Cinacalcet 194; Etelcalcetide 241
• Number of Participants With cCa < 7.5 mg/dL At Any Time During the Study (Other pre specified), Count of participants, Participants: Cinacalcet 61; Etelcalcetide 109
• Number of Participants With Treatment-emergent Symptomatic Hypocalcemia During the Study (Other pre specified), Count of participants, Participants: Cinacalcet 15; Etelcalcetide 35
• Number of Participants Who Developed Antibodies to Etelcalcetide (Other pre specified), Count of participants, Participants: Etelcalcetide 18
• Number of Participants With Treatment-emergent Adverse Events (Other pre specified), Count of participants, Participants: Cinacalcet 303; Etelcalcetide 306

Adverse events

Time frame: From first dose of study drug to 30 days after last dose (up to 26 weeks + 30 days).

Serious adverse events by term

46 more terms not shown.

Other adverse events by term

• Study Protocol (PDF, 2018-11-27)
• Statistical Analysis Plan (PDF, 2020-04-14)

• MD, Study director, Amgen