Trial Outcomes & Findings for Efficacy and Safety of Etelcalcetide (AMG 416) in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease (CKD) on Hemodialysis (NCT NCT01788046)

NCT ID: NCT01788046

Last Updated: 2019-08-20

Results Overview

Participants who did not have any scheduled assessments during the EAP were considered non-responders.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

515 participants

Primary outcome timeframe

Baseline and the efficacy assessment phase (EAP; defined as Weeks 20 to 27, inclusive).

Results posted on

2019-08-20

Participant Flow

This study was conducted at 97 centers in the US, Canada, Europe, Israel, the Russian Federation, and Australia. The first participant was enrolled on 12 March 2013, and the last participant 07 October 2013.

Eligible participants were randomized 1:1 to etelcalcetide or placebo. Randomization was stratified by screening parathyroid hormone (PTH) (\< 600 pg/mL, 600 to ≤ 1000 pg/mL, and \> 1000 pg/mL), prior cinacalcet use and region (North America or non-North America).

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.	Etelcalcetide Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW for 26 weeks.
Overall Study STARTED	260	255
Overall Study Received Treatment	259	252
Overall Study COMPLETED	204	218
Overall Study NOT COMPLETED	56	37

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.	Etelcalcetide Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW for 26 weeks.
Overall Study Withdrawal by Subject	12	12
Overall Study Lost to Follow-up	12	19
Overall Study Death	7	5
Overall Study Protocol Specified Criteria	25	1

Baseline Characteristics

Efficacy and Safety of Etelcalcetide (AMG 416) in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease (CKD) on Hemodialysis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=260 Participants Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.	Etelcalcetide n=255 Participants Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW for 26 weeks.	Total n=515 Participants Total of all reporting groups
Age, Continuous	59.0 years STANDARD_DEVIATION 13.9 • n=5 Participants	58.4 years STANDARD_DEVIATION 14.6 • n=7 Participants	58.7 years STANDARD_DEVIATION 14.3 • n=5 Participants
Sex: Female, Male Female	95 Participants n=5 Participants	93 Participants n=7 Participants	188 Participants n=5 Participants
Sex: Female, Male Male	165 Participants n=5 Participants	162 Participants n=7 Participants	327 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Asian	6 participants n=5 Participants	13 participants n=7 Participants	19 participants n=5 Participants
Race/Ethnicity, Customized Black (or African American)	80 participants n=5 Participants	64 participants n=7 Participants	144 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	3 participants n=5 Participants	7 participants n=7 Participants	10 participants n=5 Participants
Race/Ethnicity, Customized White	169 participants n=5 Participants	163 participants n=7 Participants	332 participants n=5 Participants
Race/Ethnicity, Customized Other	2 participants n=5 Participants	6 participants n=7 Participants	8 participants n=5 Participants
Race/Ethnicity, Customized Missing	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	33 participants n=5 Participants	32 participants n=7 Participants	65 participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic/Latino	227 participants n=5 Participants	221 participants n=7 Participants	448 participants n=5 Participants
Stratification Factor: Screening Serum Parathroid Hormone < 600 pg/mL	84 participants n=5 Participants	84 participants n=7 Participants	168 participants n=5 Participants
Stratification Factor: Screening Serum Parathroid Hormone ≥ 600 to ≤ 1000 pg/mL	121 participants n=5 Participants	118 participants n=7 Participants	239 participants n=5 Participants
Stratification Factor: Screening Serum Parathroid Hormone > 1000 pg/mL	55 participants n=5 Participants	53 participants n=7 Participants	108 participants n=5 Participants
Stratification Factor: Cinacalcet Use Within 8 Weeks of Randomization Yes	33 participants n=5 Participants	29 participants n=7 Participants	62 participants n=5 Participants
Stratification Factor: Cinacalcet Use Within 8 Weeks of Randomization No	227 participants n=5 Participants	226 participants n=7 Participants	453 participants n=5 Participants
Stratification Factor: Region North America	150 participants n=5 Participants	146 participants n=7 Participants	296 participants n=5 Participants
Stratification Factor: Region Non-North America	110 participants n=5 Participants	109 participants n=7 Participants	219 participants n=5 Participants
Parathyroid Hormone	851.7 pg/mL STANDARD_DEVIATION 552.0 • n=5 Participants	845.0 pg/mL STANDARD_DEVIATION 464.3 • n=7 Participants	848.4 pg/mL STANDARD_DEVIATION 510.0 • n=5 Participants
Phosphorus	5.83 mg/dL STANDARD_DEVIATION 1.45 • n=5 Participants	5.76 mg/dL STANDARD_DEVIATION 1.60 • n=7 Participants	5.79 mg/dL STANDARD_DEVIATION 1.53 • n=5 Participants
Corrected Calcium (cCa)	9.70 mg/dL STANDARD_DEVIATION 0.69 • n=5 Participants	9.63 mg/dL STANDARD_DEVIATION 0.65 • n=7 Participants	9.66 mg/dL STANDARD_DEVIATION 0.67 • n=5 Participants
Corrected Calcium Phosphorus Product (cCa x P)	56.37 mg²/dL² STANDARD_DEVIATION 14.50 • n=5 Participants	55.30 mg²/dL² STANDARD_DEVIATION 15.27 • n=7 Participants	55.84 mg²/dL² STANDARD_DEVIATION 14.88 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and the efficacy assessment phase (EAP; defined as Weeks 20 to 27, inclusive).

Population: The full analysis set, consisting of all randomized participants

Participants who did not have any scheduled assessments during the EAP were considered non-responders.

Outcome measures

Outcome measures
Measure	Placebo n=260 Participants Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.	Etelcalcetide n=255 Participants Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW for 26 weeks.
Percentage of Participants With > 30% Decrease From Baseline in Mean PTH During the Efficacy Assessment Phase	9.6 percentage of participants	75.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline and the efficacy assessment phase (Week 20 to Week 27)

Population: Full analysis set

Participants who had no scheduled assessments during the EAP were considered non-responders.

Outcome measures

Outcome measures
Measure	Placebo n=260 Participants Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.	Etelcalcetide n=255 Participants Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW for 26 weeks.
Percentage of Participants With Mean Predialysis Parathyroid Hormone ≤ 300 pg/mL During the Efficacy Assessment Phase	4.6 percentage of participants	53.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline and the Efficacy Assessment Phase (Week 20 to Week 27)

Population: Full analysis set participants with observed data

Outcome measures

Outcome measures
Measure	Placebo n=237 Participants Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.	Etelcalcetide n=227 Participants Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW for 26 weeks.
Percent Change From Baseline in Predialysis PTH During the Efficacy Assessment Phase	13.72 percent change Standard Error 2.50	-57.39 percent change Standard Error 1.91

SECONDARY outcome

Timeframe: Baseline and the efficacy assessment phase (Week 20 to Week 27)

Population: Full analysis set participants with observed data

Outcome measures

Outcome measures
Measure	Placebo n=237 Participants Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.	Etelcalcetide n=227 Participants Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW for 26 weeks.
Percent Change From Baseline in Predialysis Corrected Calcium During the Efficacy Assessment Phase	0.58 percent change Standard Error 0.29	-6.69 percent change Standard Error 0.55

SECONDARY outcome

Timeframe: Baseline and the efficacy assessment phase (Week 20 to Week 27)

Population: Full analysis set participants with observed data

Outcome measures

Outcome measures
Measure	Placebo n=234 Participants Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.	Etelcalcetide n=223 Participants Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW for 26 weeks.
Percent Change From Baseline in Predialysis Corrected Calcium Phosphorus Product (cCa x P) During the Efficacy Assessment Phase	-1.06 percent change Standard Error 1.42	-15.84 percent change Standard Error 1.57

SECONDARY outcome

Timeframe: Baseline and the efficacy assessment phase (Week 20 to Week 27)

Population: Full analysis set participants with observed data

Outcome measures

Outcome measures
Measure	Placebo n=234 Participants Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.	Etelcalcetide n=223 Participants Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW for 26 weeks.
Percent Change From Baseline in Predialysis Phosphorus During the Efficacy Assessment Phase	-1.60 percent change Standard Error 1.42	-9.63 percent change Standard Error 1.61

Adverse Events

Placebo

Serious events: 71 serious events

Other events: 132 other events

Deaths: 0 deaths

Etelcalcetide

Serious events: 62 serious events

Other events: 199 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=259 participants at risk Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.	Etelcalcetide n=252 participants at risk Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW for 26 weeks.
Blood and lymphatic system disorders Anaemia	5.0% 13/259 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.2% 8/252 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Diarrhoea	9.7% 25/259 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	13.9% 35/252 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Nausea	6.9% 18/259 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	9.1% 23/252 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Vomiting	3.1% 8/259 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.5% 19/252 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Upper respiratory tract infection	5.8% 15/259 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.2% 13/252 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Arteriovenous fistula site complication	4.6% 12/259 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.3% 16/252 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Blood calcium decreased	12.0% 31/259 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	66.7% 168/252 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/259 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.7% 17/252 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Arthralgia	5.8% 15/259 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.4% 11/252 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Back pain	3.5% 9/259 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.6% 14/252 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Muscle spasms	6.2% 16/259 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	11.1% 28/252 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	4.2% 11/259 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.9% 20/252 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Cough	5.8% 15/259 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.0% 10/252 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypertension	4.6% 12/259 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.1% 18/252 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypotension	5.8% 15/259 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.6% 14/252 • From Day 1 until 30 days after the last dose; the treatment period was 26 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.