Hyperparathyroidism, Secondary
Conditions
Keywords
Secondary Hyperparathyroidism (SHPT), chronic kidney disease (CKD), hemodialysis, parathyroid hormone (PTH), hypocalcemia, bone and mineral metabolism
Brief summary
This is a multicenter, multiple-dose, single-arm, open-label study to assess the impact on serum corrected calcium levels when switching patients from cinacalcet to etelcalcetide (AMG 416).
Interventions
DRUGEtelcalcetide
Etelcalcetide is provided as a sterile lyophilized powder to be reconstituted with sterile water for injection.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Subject is 18 years of age or older at the time of informed consent. * Subject must be receiving maintenance hemodialysis 3 times weekly for at least 8 weeks. * Subject must have SHPT as defined by having a mean of 3 consecutive central laboratory screening predialysis serum parathyroid hormone (PTH) values ≥ 200 pg/mL, with measurements obtained from 3 different calendar weeks in the 4-week screening period while receiving cinacalcet. * Subject must have a mean of 3 consecutive central laboratory screening predialysis serum corrected calcium (cCa) values ≥ 7.5 mg/dL, with measurements obtained from 3 different calendar weeks in the 4-week screening period while receiving cinacalcet. * Subject must be on a stable dose of cinacalcet before screening (defined as no dose change within the 4 weeks prior to screening). * Other Inclusion Criteria may apply.
Exclusion criteria
* Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s). * Subject has received AMG 416 in a prior clinical trial of AMG 416 (also known as KAI-4169). * Subject has known sensitivity to any of the products or components of AMG 416 to be administered during dosing. * Subject is unwilling to use effective contraception during the study, and for women, up to a period of up to 3 months after the last dose of AMG 416. * Subject is pregnant or nursing. * Anticipated or scheduled parathyroidectomy during the study period. * Subject has received a parathyroidectomy within 6 months prior to dosing. * Other
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Serum Corrected Calcium < 7.5 mg/dL During the 4-week Treatment Period | 4 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in Parathyroid Hormone During the Treatment Period | Baseline and weeks 2, 3 and 4 |
| Percentage of Participants With Serum Corrected Calcium < 8.3 mg/dL During the 4-week Treatment Period | 4 weeks |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From the first dose of study drug up to 30 days after the last dose; 8 weeks | — |
| Percentage of Participants With Symptomatic Hypocalcemia During the 4-week Treatment Period | From the first dose of study drug up to 30 days after the last dose; 8 weeks | Hpocalcemia was used for events of decreased calcium accompanied by clinical signs and symptoms of hypocalcemia. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 33 centers in the United States. Participants were enrolled from 1 September 2013 to 9 December 2013. Participants were required to be on a stable dose of daily oral cinacalcet for a minimum of 4 weeks before screening, and during the 4 weeks of screening.
Pre-assignment details
Upon enrollment, participants underwent a washout period of a minimum of 7 days, wherein no cinacalcet use was allowed. Participants who had a serum corrected calcium ≥ 8.3 mg/dL during the washout period entered the treatment phase and were categorized based on their pre-washout, screening cinacalcet daily dose level (30 mg, 60 mg or ≥ 90 mg).
Participants by arm
| Arm | Count |
|---|---|
| Etelcalcetide Participants were treated with 5 mg etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session three times per week (TIW) for 4 weeks. | 147 |
| Total | 147 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Protocol Specified Criteria | 10 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Etelcalcetide |
|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 14 |
| Age, Customized < 65 years | 106 participants |
| Age, Customized ≥ 65 years | 41 participants |
| Corrected Calcium | 9.81 mg/dL STANDARD_DEVIATION 0.75 |
| Ethnicity Hispanic/Latino | 39 participants |
| Ethnicity Not Hispanic/Latino | 108 participants |
| Parathyroid Hormone | 786.3 pg/mL STANDARD_DEVIATION 467.8 |
| Phosphorus | 5.88 mg/dL STANDARD_DEVIATION 1.71 |
| Race American Indian or Alaska Native | 1 participants |
| Race Asian | 12 participants |
| Race Black (or African American) | 68 participants |
| Race Native Hawaiian or Other Pacific Islander | 2 participants |
| Race White | 64 participants |
| Sex: Female, Male Female | 55 Participants |
| Sex: Female, Male Male | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 148 |
| serious Total, serious adverse events | 17 / 148 |
Outcome results
Primary
Percentage of Participants With Serum Corrected Calcium < 7.5 mg/dL During the 4-week Treatment Period
Time frame: 4 weeks
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etelcalcetide | Percentage of Participants With Serum Corrected Calcium < 7.5 mg/dL During the 4-week Treatment Period | 0.7 percentage of participants |
Secondary
Percentage of Participants With Serum Corrected Calcium < 8.3 mg/dL During the 4-week Treatment Period
Time frame: 4 weeks
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etelcalcetide | Percentage of Participants With Serum Corrected Calcium < 8.3 mg/dL During the 4-week Treatment Period | 15.6 percentage of participants |
Secondary
Percent Change From Baseline in Parathyroid Hormone During the Treatment Period
Time frame: Baseline and weeks 2, 3 and 4
Population: Full analysis set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Etelcalcetide | Percent Change From Baseline in Parathyroid Hormone During the Treatment Period | Week 2 (n = 125) | -3.9 percent change | Standard Error 2.6 |
| Etelcalcetide | Percent Change From Baseline in Parathyroid Hormone During the Treatment Period | Week 3 (n = 131) | -7.8 percent change | Standard Error 3.1 |
| Etelcalcetide | Percent Change From Baseline in Parathyroid Hormone During the Treatment Period | Week 4 (n = 123) | -10.9 percent change | Standard Error 2.9 |
Other Pre-specified
Number of Participants With Adverse Events
Time frame: From the first dose of study drug up to 30 days after the last dose; 8 weeks
Population: All participants who received at least one dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Etelcalcetide | Number of Participants With Adverse Events | Any adverse event (AE) | 72 participants |
| Etelcalcetide | Number of Participants With Adverse Events | Serious adverse event (SAE) | 17 participants |
| Etelcalcetide | Number of Participants With Adverse Events | AE leading to discontinuation of etelcalcetide | 2 participants |
| Etelcalcetide | Number of Participants With Adverse Events | Fatal adverse event | 1 participants |
| Etelcalcetide | Number of Participants With Adverse Events | Treatment-related adverse event | 11 participants |
Other Pre-specified
Percentage of Participants With Symptomatic Hypocalcemia During the 4-week Treatment Period
Hpocalcemia was used for events of decreased calcium accompanied by clinical signs and symptoms of hypocalcemia.
Time frame: From the first dose of study drug up to 30 days after the last dose; 8 weeks
Population: Participants who received at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etelcalcetide | Percentage of Participants With Symptomatic Hypocalcemia During the 4-week Treatment Period | 0.0 percentage of participants |