Hyperparathyroidism, Secondary
Conditions
Keywords
Secondary Hyperparathyroidism (SHPT), chrominc kidney disease (CKD), hemodialysis
Brief summary
This is a multicenter, single-arm, extension study to characterize the long-term safety and tolerability of etelcalcetide in the treatment of Secondary Hyperparathyroidism (SHPT) in adults with Chronic Kidney Disease (CKD) on hemodialysis.
Detailed description
This is a multicenter, single-arm, extension study in which adults with secondary hyperparathyroidism currently receiving hemodialysis and previously treated in Amgen studies 20120231 (NCT01785875), 20120334 (NCT01576146), or 20120360 (NCT01896232) will continue to be treated with etelcalcetide until approximately 2.5 years after the first participant was enrolled.
Interventions
DRUGEtelcalcetide
Etelcalcetide was supplied as a sterile, preservative-free, ready-to-administer aqueous solution.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 110 Years
Healthy volunteers
No
Inclusion criteria
* Subject has provided informed consent prior to initiation of any study-specific activities/procedures * Subject has completed treatment in Study 20120231 (also known as KAI-4169-008) or Study 20120360, or has participated in Study 20120334 (also known as KAI-4169-005-01) * Female subjects who are: post-menopausal (post-menopausal is defined as no menses for the previous 1 year and over the age of 50 years), surgically sterilized, have a medical condition that prevents pregnancy, remain abstinent, or are willing to use an acceptable method of effective contraception during the study and for 3 months after the last dose. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 2 weeks prior to the first dose of AMG 416 in the current study * Subject must be receiving hemodialysis 3 or 4 times weekly for at least 3 months
Exclusion criteria
* Currently receiving treatment in another investigational device or drug study (other than in one of the designated parent studies) * Subject has known sensitivity to any of the products or components to be administered during dosing * Subject has been prescribed cinacalcet by the primary nephrologist between the conclusion of the parent study and the start of dosing with AMG 416 in the current study * Subject is receiving dialysis prescription dialysate calcium concentration \< 2.25 mEq/L * Subject is pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From the date of first dose of etelcalcetide (in the current study) and up to 30 days after the last dose; median duration of treatment was 563 days. | A serious adverse event is an AE that met at least 1 of the following 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. The relationship of each AE to study treatment was assessed by the investigator. The following AE grading scale was used: Mild: Transient or mild discomfort; no limitation in activity; no medical intervention/therapy required Moderate: Mild to moderate limitation in activity-some assistance may be needed; no or minimal medical intervention/therapy required Severe: Marked limitation in activity, some assistance usually required; medical intervention/therapy required, hospitalization possible Life-threatening: Extreme limitation in activity, significant assistance required, significant medical intervention/therapy required, hospitalization probable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Parathyroid Hormone Levels Between Two to Nine-times the Upper Limit of Normal | Months 6, 12, and 18 | The percentage of participants who maintained plasma parathyroid hormone (PTH) levels within the Kidney Disease Improving Global Outcomes (KDIGO) recommended range of not less than 2x the upper limit of normal (ULN) and not greater than 9x the ULN at months 6, 12, and 18, with the ULN based on the reference range of the assay used at the individual clinical site. |
| Percentage of Participants With Serum Phosphorus ≤ the ULN | Months 6, 12, and 18 | Percentage of participants with serum phosphorus less than or equal to the upper limit of normal for the assay used. |
| Percentage of Participants With Serum Corrected Calcium < 7.5 mg/dL | From day 1 to months 6, 12, and 18 | The percentage of participants with serum corrected calcium (cCa) reported for cumulative time intervals from day 1 through months 6, 12, and 18, using the participant's lowest recorded corrected calcium value during the time interval. If serum albumin was less than 4.0 g/dL, serum calcium was corrected according to the following formula: cCa (mg/dL) = total calcium (mg/dL) + (4 - albumin \[g/dL\])\*0.8. If serum albumin was \> 4.0 g/dL no correction was made. |
| Number of Participants With Shifts From Baseline Grade 0 or 1 to Postbaseline Grade 3 or 4 for Laboratory Parameters | Baseline to end of treatment; median duration of treatment was 563 days. | The Common Terminology Criteria for Adverse Events (CTCAE) grades for laboratory parameter values were defined based on the upper/lower limit of normal from the local laboratories contracted by the study centers. |
| Number of Participants Who Developed Positive Binding Anti-Etelcalcetide Antibodies | Baseline and every 6 months (up to 24 months) | The number of participants who were binding antibody positive post-baseline with a negative or no result at baseline (where baseline for participants previously treated with etelcalcetide is Day 1 of the first study in which they were exposed to etelcalcetide and for participants previously treated with cinacalcet is the ending time point for study 20120360). |
Countries
Australia, Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Latvia, Lithuania, Netherlands, New Zealand, Poland, Portugal, Russia, Spain, Sweden, Switzerland, Turkey (Türkiye), United States
Participant flow
Recruitment details
The study was conducted at 229 study centers in Europe, Australia, New Zealand, and North America
Pre-assignment details
A total of 902 participants were enrolled in Study 20130213: 215 and 200 participants from the cinacalcet and etelcalcetide groups of the double-blind parent Study 20120360 (NCT01896232), respectively, and 487 participants from the open-label parent Studies 20120231 (NCT01785875) and 20120334 (NCT01576146).
Participants by arm
| Arm | Count |
|---|---|
| Etelcalcetide Participants received etelcalcetide three times a week (TIW) by bolus injection at the end of hemodialysis. The minimum etelcalcetide dose in this study was 2.5 mg and the maximum dose was 15 mg. Etelcalcetide dose was titrated to maintain parathyroid hormone levels within 2x to 9x the upper limit of normal based on the reference range of the assay used at the individual study center. | 884 |
| Total | 884 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 92 |
| Overall Study | Lost to Follow-up | 65 |
| Overall Study | Ongoing | 5 |
| Overall Study | Sponsor Decision | 5 |
| Overall Study | Withdrawal by Subject | 137 |
Baseline characteristics
| Characteristic | Etelcalcetide |
|---|---|
| Age, Continuous | 57.7 years STANDARD_DEVIATION 14.3 |
| Age, Customized < 65 years | 582 Participants |
| Age, Customized ≥ 65 years | 302 Participants |
| Albumin Corrected Calcium | 8.94 mg/dL STANDARD_DEVIATION 0.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 78 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 806 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Parathyroid Hormone | 528.3 pg/mL STANDARD_DEVIATION 566.4 |
| Phosphorus | 5.24 mg/dL STANDARD_DEVIATION 1.69 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Asian | 14 Participants |
| Race/Ethnicity, Customized Black | 192 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 9 Participants |
| Race/Ethnicity, Customized Other | 11 Participants |
| Race/Ethnicity, Customized White | 657 Participants |
| Sex: Female, Male Female | 357 Participants |
| Sex: Female, Male Male | 527 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 519 / 884 |
| serious Total, serious adverse events | 436 / 884 |
Outcome results
Primary
Number of Participants With Adverse Events
A serious adverse event is an AE that met at least 1 of the following 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. The relationship of each AE to study treatment was assessed by the investigator. The following AE grading scale was used: Mild: Transient or mild discomfort; no limitation in activity; no medical intervention/therapy required Moderate: Mild to moderate limitation in activity-some assistance may be needed; no or minimal medical intervention/therapy required Severe: Marked limitation in activity, some assistance usually required; medical intervention/therapy required, hospitalization possible Life-threatening: Extreme limitation in activity, significant assistance required, significant medical intervention/therapy required, hospitalization probable.
Time frame: From the date of first dose of etelcalcetide (in the current study) and up to 30 days after the last dose; median duration of treatment was 563 days.
Population: Participants who received at least 1 dose of etelcalcetide in the current study (20130213).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Etelcalcetide | Number of Participants With Adverse Events | Mild adverse events | 123 participants |
| Etelcalcetide | Number of Participants With Adverse Events | Any adverse event | 768 participants |
| Etelcalcetide | Number of Participants With Adverse Events | Serious adverse events | 436 participants |
| Etelcalcetide | Number of Participants With Adverse Events | Treatment-related adverse events | 287 participants |
| Etelcalcetide | Number of Participants With Adverse Events | Serious treatment-related adverse events | 4 participants |
| Etelcalcetide | Number of Participants With Adverse Events | AEs leading to discontinuation of etelcalcetide | 41 participants |
| Etelcalcetide | Number of Participants With Adverse Events | Fatal adverse events | 89 participants |
| Etelcalcetide | Number of Participants With Adverse Events | Moderate adverse events | 219 participants |
| Etelcalcetide | Number of Participants With Adverse Events | Severe adverse events | 324 participants |
| Etelcalcetide | Number of Participants With Adverse Events | Life-threatening adverse events | 102 participants |
Secondary
Number of Participants Who Developed Positive Binding Anti-Etelcalcetide Antibodies
The number of participants who were binding antibody positive post-baseline with a negative or no result at baseline (where baseline for participants previously treated with etelcalcetide is Day 1 of the first study in which they were exposed to etelcalcetide and for participants previously treated with cinacalcet is the ending time point for study 20120360).
Time frame: Baseline and every 6 months (up to 24 months)
Population: Participants who received at least 1 dose of etelcalcetide in the current study with a post-baseline antibody result during this study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etelcalcetide | Number of Participants Who Developed Positive Binding Anti-Etelcalcetide Antibodies | 111 participants |
Secondary
Number of Participants With Shifts From Baseline Grade 0 or 1 to Postbaseline Grade 3 or 4 for Laboratory Parameters
The Common Terminology Criteria for Adverse Events (CTCAE) grades for laboratory parameter values were defined based on the upper/lower limit of normal from the local laboratories contracted by the study centers.
Time frame: Baseline to end of treatment; median duration of treatment was 563 days.
Population: Participants who received at least 1 dose of etelcalcetide in the current study (20130213).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Etelcalcetide | Number of Participants With Shifts From Baseline Grade 0 or 1 to Postbaseline Grade 3 or 4 for Laboratory Parameters | Increased Alanine Aminotransferase Grade 1 to 3 | 1 participants |
| Etelcalcetide | Number of Participants With Shifts From Baseline Grade 0 or 1 to Postbaseline Grade 3 or 4 for Laboratory Parameters | Increased Alkaline Phosphatase Grade 1 to 3 | 2 participants |
| Etelcalcetide | Number of Participants With Shifts From Baseline Grade 0 or 1 to Postbaseline Grade 3 or 4 for Laboratory Parameters | Increased Aspartate Aminotransferase Grade 1 to 3 | 1 participants |
| Etelcalcetide | Number of Participants With Shifts From Baseline Grade 0 or 1 to Postbaseline Grade 3 or 4 for Laboratory Parameters | Decreased Corrected Calcium Grade 1 to 3 | 18 participants |
| Etelcalcetide | Number of Participants With Shifts From Baseline Grade 0 or 1 to Postbaseline Grade 3 or 4 for Laboratory Parameters | Decreased Corrected Calcium Grade 1 to 4 | 2 participants |
| Etelcalcetide | Number of Participants With Shifts From Baseline Grade 0 or 1 to Postbaseline Grade 3 or 4 for Laboratory Parameters | Decreased ionized Calcium Grade 1 to 3 | 1 participants |
| Etelcalcetide | Number of Participants With Shifts From Baseline Grade 0 or 1 to Postbaseline Grade 3 or 4 for Laboratory Parameters | Decreased ionized Calcium Grade 1 to 4 | 2 participants |
| Etelcalcetide | Number of Participants With Shifts From Baseline Grade 0 or 1 to Postbaseline Grade 3 or 4 for Laboratory Parameters | Decreased Phosphorous Grade 1 to 3 | 1 participants |
Secondary
Percentage of Participants With Parathyroid Hormone Levels Between Two to Nine-times the Upper Limit of Normal
The percentage of participants who maintained plasma parathyroid hormone (PTH) levels within the Kidney Disease Improving Global Outcomes (KDIGO) recommended range of not less than 2x the upper limit of normal (ULN) and not greater than 9x the ULN at months 6, 12, and 18, with the ULN based on the reference range of the assay used at the individual clinical site.
Time frame: Months 6, 12, and 18
Population: Participants who received at least 1 dose of etelcalcetide in the current study (20130213) with available data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Etelcalcetide | Percentage of Participants With Parathyroid Hormone Levels Between Two to Nine-times the Upper Limit of Normal | Month 6 | 67.0 percentage of participants |
| Etelcalcetide | Percentage of Participants With Parathyroid Hormone Levels Between Two to Nine-times the Upper Limit of Normal | Month 12 | 73.2 percentage of participants |
| Etelcalcetide | Percentage of Participants With Parathyroid Hormone Levels Between Two to Nine-times the Upper Limit of Normal | Month 18 | 71.9 percentage of participants |
Secondary
Percentage of Participants With Serum Corrected Calcium < 7.5 mg/dL
The percentage of participants with serum corrected calcium (cCa) reported for cumulative time intervals from day 1 through months 6, 12, and 18, using the participant's lowest recorded corrected calcium value during the time interval. If serum albumin was less than 4.0 g/dL, serum calcium was corrected according to the following formula: cCa (mg/dL) = total calcium (mg/dL) + (4 - albumin \[g/dL\])\*0.8. If serum albumin was \> 4.0 g/dL no correction was made.
Time frame: From day 1 to months 6, 12, and 18
Population: Participants who received at least 1 dose of etelcalcetide in the current study (20130213) with available data at the beginning of the time interval.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Etelcalcetide | Percentage of Participants With Serum Corrected Calcium < 7.5 mg/dL | Day 1 to Month 6 | 9.5 percentage of participants |
| Etelcalcetide | Percentage of Participants With Serum Corrected Calcium < 7.5 mg/dL | Day 1 to Month 12 | 14.1 percentage of participants |
| Etelcalcetide | Percentage of Participants With Serum Corrected Calcium < 7.5 mg/dL | Day 1 to Month 18 | 16.3 percentage of participants |
Secondary
Percentage of Participants With Serum Phosphorus ≤ the ULN
Percentage of participants with serum phosphorus less than or equal to the upper limit of normal for the assay used.
Time frame: Months 6, 12, and 18
Population: Participants who received at least 1 dose of etelcalcetide in the current study (20130213) with available data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Etelcalcetide | Percentage of Participants With Serum Phosphorus ≤ the ULN | Month 6 | 39.4 percentage of participants |
| Etelcalcetide | Percentage of Participants With Serum Phosphorus ≤ the ULN | Month 12 | 40.0 percentage of participants |
| Etelcalcetide | Percentage of Participants With Serum Phosphorus ≤ the ULN | Month 18 | 36.8 percentage of participants |