Trial Outcomes & Findings for Efficacy and Safety of Etelcalcetide (AMG 416) in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease on Hemodialysis (NCT NCT01785849)

NCT ID: NCT01785849

Last Updated: 2019-08-26

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

508 participants

Primary outcome timeframe

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

Results posted on

2019-08-26

Participant Flow

This study was conducted at 111 centers in the US, Canada, Europe, Israel, Russian Federation, and Australia. The first participant was enrolled on 12 March 2013 and the last participant enrolled on 08 November 2013.

Eligible participants were randomized in a 1:1 ratio to etelcalcetide or placebo. Randomization was stratified by mean 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. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.
Overall Study STARTED	254	254
Overall Study Received Treatment	254	251
Overall Study COMPLETED	193	220
Overall Study NOT COMPLETED	61	34

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. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.
Overall Study Death	7	9
Overall Study Protocol Specified Criteria	29	1
Overall Study Withdrawal by Subject	15	12
Overall Study Sponsor Decision	0	1
Overall Study Lost to Follow-up	10	11

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=254 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=254 Participants Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session, TIW, for 26 weeks. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.	Total n=508 Participants Total of all reporting groups
Age, Continuous	57.1 years STANDARD_DEVIATION 14.5 • n=5 Participants	58.4 years STANDARD_DEVIATION 14.6 • n=7 Participants	57.7 years STANDARD_DEVIATION 14.6 • n=5 Participants
Sex: Female, Male Female	114 Participants n=5 Participants	103 Participants n=7 Participants	217 Participants n=5 Participants
Sex: Female, Male Male	140 Participants n=5 Participants	151 Participants n=7 Participants	291 Participants n=5 Participants
Race American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race Asian	3 participants n=5 Participants	5 participants n=7 Participants	8 participants n=5 Participants
Race Black (or African American)	69 participants n=5 Participants	72 participants n=7 Participants	141 participants n=5 Participants
Race Native Hawaiian or Other Pacific Islander	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Race White	175 participants n=5 Participants	173 participants n=7 Participants	348 participants n=5 Participants
Race Other	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
Race Missing	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Stratification Factor: Mean Screening Serum Parathyroid Hormone (PTH) < 600 pg/mL	84 participants n=5 Participants	87 participants n=7 Participants	171 participants n=5 Participants
Stratification Factor: Mean Screening Serum Parathyroid Hormone (PTH) ≥ 600 to ≤ 1000 pg/mL	114 participants n=5 Participants	115 participants n=7 Participants	229 participants n=5 Participants
Stratification Factor: Mean Screening Serum Parathyroid Hormone (PTH) > 1000 pg/mL	56 participants n=5 Participants	52 participants n=7 Participants	108 participants n=5 Participants
Stratification Factor: Cinacalcet Use Within 8 Weeks of Randomization Yes	34 participants n=5 Participants	33 participants n=7 Participants	67 participants n=5 Participants
Stratification Factor: Cinacalcet Use Within 8 Weeks of Randomization No	220 participants n=5 Participants	221 participants n=7 Participants	441 participants n=5 Participants
Stratification Factor: Region North America	129 participants n=5 Participants	132 participants n=7 Participants	261 participants n=5 Participants
Stratification Factor: Region Non-North America	125 participants n=5 Participants	122 participants n=7 Participants	247 participants n=5 Participants
Parathyroid Hormone (PTH)	819.7 pg/mL STANDARD_DEVIATION 386.0 • n=5 Participants	848.7 pg/mL STANDARD_DEVIATION 520.4 • n=7 Participants	834.2 pg/mL STANDARD_DEVIATION 457.9 • n=5 Participants
Phosphorus	5.78 mg/dL STANDARD_DEVIATION 1.60 • n=5 Participants	5.95 mg/dL STANDARD_DEVIATION 1.59 • n=7 Participants	5.87 mg/dL STANDARD_DEVIATION 1.59 • n=5 Participants
Corrected Calcium	9.61 mg/dL STANDARD_DEVIATION 0.60 • n=5 Participants	9.65 mg/dL STANDARD_DEVIATION 0.66 • n=7 Participants	9.63 mg/dL STANDARD_DEVIATION 0.63 • n=5 Participants
Corrected Calcium Phosphorus Product (cCa x P)	55.54 mg²/dL² STANDARD_DEVIATION 15.81 • n=5 Participants	57.37 mg²/dL² STANDARD_DEVIATION 15.51 • n=7 Participants	56.46 mg²/dL² STANDARD_DEVIATION 15.67 • 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=254 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=254 Participants Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session, TIW, for 26 weeks. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.
Percentage of Participants With a > 30% Decrease From Baseline in Mean PTH During the Efficacy Assessment Phase	8.3 percentage of participants	74.0 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=254 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=254 Participants Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session, TIW, for 26 weeks. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.
Percentage of Participants With Mean Predialysis Parathyroid Hormone ≤ 300 pg/mL During the Efficacy Assessment Phase	5.1 percentage of participants	49.6 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=219 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=229 Participants Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session, TIW, for 26 weeks. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.
Percent Change From Baseline in Predialysis PTH During the Efficacy Assessment Phase	13.00 percent change Standard Error 2.81	-55.11 percent change Standard Error 1.94

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=219 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=229 Participants Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session, TIW, for 26 weeks. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.
Percent Change From Baseline in Predialysis Corrected Calcium During the Efficacy Assessment Phase	1.18 percent change Standard Error 0.29	-7.29 percent change Standard Error 0.53

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=213 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. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.
Percent Change From Baseline in Predialysis Corrected Calcium Phosphorus Product During the Efficacy Assessment Phase	-0.19 percent change Standard Error 1.44	-14.34 percent change Standard Error 2.06

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=214 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. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.
Percent Change From Baseline in Predialysis Phosphorus During the Efficacy Assessment Phase	-1.31 percent change Standard Deviation 1.42	-7.71 percent change Standard Deviation 2.16

Adverse Events

Placebo

Serious events: 78 serious events

Other events: 110 other events

Deaths: 0 deaths

Etelcalcetide

Serious events: 68 serious events

Other events: 194 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=254 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=251 participants at risk Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session, TIW, for 26 weeks. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.
Gastrointestinal disorders Diarrhoea	6.7% 17/254 • 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.	7.2% 18/251 • 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	5.1% 13/254 • 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.	12.4% 31/251 • 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	7.1% 18/254 • 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.	10.0% 25/251 • 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 Nasopharyngitis	5.1% 13/254 • 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% 11/251 • 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	5.5% 14/254 • 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% 11/251 • 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	8.3% 21/254 • 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.	61.0% 153/251 • 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	0.39% 1/254 • 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.	7.2% 18/251 • 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	7.1% 18/254 • 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.	12.0% 30/251 • 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 Pain in extremity	4.3% 11/254 • 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.	6.8% 17/251 • 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	7.9% 20/254 • 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.	7.2% 18/251 • 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 Paraesthesia	1.2% 3/254 • 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% 13/251 • 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	6.3% 16/254 • 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.	4.8% 12/251 • 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	3.9% 10/254 • 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% 14/251 • 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.

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