Trial Outcomes & Findings for The Effect of Etelcalcetide on CKD-MBD (NCT NCT03960437)

NCT ID: NCT03960437

Last Updated: 2023-09-21

Results Overview

Mean percent change in parathyroid hormone (PTH) levels will be calculated.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 22 participants
• Primary outcome timeframe: Baseline and 9 months
• Results posted on: 2023-09-21

Participant Flow

Participant milestones

Measure	Study Participant Every study participant will receive etelcalcetide prescribed by their treating physician for the duration of the study. Etelcalcetide: Administered intravenously at the end of each dialysis session. Dosing ranges from 5 mg to 15 mg set by the patient's physician.
Overall Study STARTED	22
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Measure	Study Participant Every study participant will receive etelcalcetide prescribed by their treating physician for the duration of the study. Etelcalcetide: Administered intravenously at the end of each dialysis session. Dosing ranges from 5 mg to 15 mg set by the patient's physician.
Overall Study Removed by PI	4
Overall Study Lost to Follow-up	2
Overall Study Withdrawal by Subject	1
Overall Study Death	2

Baseline Characteristics

The Effect of Etelcalcetide on CKD-MBD

Baseline characteristics by cohort

Measure	Study Participant n=22 Participants Every study participant will receive etelcalcetide prescribed by their treating physician for the duration of the study. Etelcalcetide: Administered intravenously at the end of each dialysis session. Dosing ranges from 5 mg to 15 mg set by the patient's physician.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	15 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Washout of Cinacalcet Required	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 9 months

Population: Only includes participants who completed the study

Mean percent change in parathyroid hormone (PTH) levels will be calculated.

Outcome measures

Measure	Study Participant n=13 Participants Every study participant will receive etelcalcetide prescribed by their treating physician for the duration of the study. Etelcalcetide: Administered intravenously at the end of each dialysis session. Dosing ranges from 5 mg to 15 mg set by the patient's physician.
Percent Change in PTH Levels Baseline	0 percentage of change in PTH levels Standard Error 0
Percent Change in PTH Levels 6 months	-54.14 percentage of change in PTH levels Standard Error 11.50
Percent Change in PTH Levels 9 months	-64.04 percentage of change in PTH levels Standard Error 8.62

PRIMARY outcome

Timeframe: Baseline and 9 months

Population: Only includes participants who completed the study.

To test if 9-months of treatment with etelcalcetide changes femoral neck areal BMD, a change in age and sex adjusted Z-Score will be calculated from baseline to 9 months. A Z-Score of zero represent the population mean and higher Z-Scores indicate a better outcome.

Outcome measures

Measure	Study Participant n=13 Participants Every study participant will receive etelcalcetide prescribed by their treating physician for the duration of the study. Etelcalcetide: Administered intravenously at the end of each dialysis session. Dosing ranges from 5 mg to 15 mg set by the patient's physician.
Change in Bone Mineral Density (BMD) of the Femoral Neck by Dual-energy X-ray Absorptiometry (DXA)	0.43 Z-score Standard Error 0.1

PRIMARY outcome

Timeframe: 9 months

Population: No data, as measured by T50, was collected. Therefore there is no data that can be reported.

The propensity to calcify soft tissues will be measured by T50 for 9 months of treatment. T50 is a novel serum-based marker that assesses the propensity of calcification in serum. Shorter T50 indicates greater propensity to calcify.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline and 9 months

Population: Only includes participants who completed the histomorphometry.

Hardness will be measured by Ramen nano-indentation and mineralization measured by histomorphometry obtained (in GPa).

Outcome measures

Measure	Study Participant n=5 Participants Every study participant will receive etelcalcetide prescribed by their treating physician for the duration of the study. Etelcalcetide: Administered intravenously at the end of each dialysis session. Dosing ranges from 5 mg to 15 mg set by the patient's physician.
Percent Change in Mean Hardness	2.68 percent of change in hardness Standard Error 8.92

SECONDARY outcome

Timeframe: Baseline and 9 months

Population: Only includes participants who completed the study.

To test if 9-months of treatment with etelcalcetide improves spine BMD, a change in age and sex adjusted Z-Score will be calculated from baseline to 9 months. A Z-Score of zero represent the population mean and higher Z-Scores indicate a better outcome.

Outcome measures

Measure	Study Participant n=13 Participants Every study participant will receive etelcalcetide prescribed by their treating physician for the duration of the study. Etelcalcetide: Administered intravenously at the end of each dialysis session. Dosing ranges from 5 mg to 15 mg set by the patient's physician.
Change in Bone Mineral Density (BMD) of the Spine by DXA	0.27 Z-score Standard Error 0.1

SECONDARY outcome

Timeframe: Baseline and 9 months

Population: Only includes participants who completed the study.

To test if 9-months of treatment with etelcalcetide improves total hip BMD, the change in age and sex adjusted Z-Score will be calculated from baseline to 9 months. A Z-Score of zero represent the population mean and higher Z-Scores indicate a better outcome.

Outcome measures

Measure	Study Participant n=13 Participants Every study participant will receive etelcalcetide prescribed by their treating physician for the duration of the study. Etelcalcetide: Administered intravenously at the end of each dialysis session. Dosing ranges from 5 mg to 15 mg set by the patient's physician.
Change in Bone Mineral Density (BMD) of Total Hip by DXA	0.12 Z-score Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline and 9 months

Population: Only includes participants who completed the bone biopsy substudy.

A quadruple label method will be used to assess effects of etelcalcetide on the bone formation rate. A tetracycline double label will be used pre-etelcalcetide and a declomycin double label will be used post-etelcalcetide in a protocol that administers label 3-days on, 12-days interlude, 3-days on. A single bone biopsy will be performed 1 to 10 days after completion of the second double label. Biopsy cores will be placed into 70% ethanol then serially dehydrated and embedded in methyl methacrylate. Four-micron thick sections will be cut and left unstained for dynamic histomorphometry. A region of interest including all trabecular bone and excluding cortical bone will be analyzed separately for each tetracycline or declomycin label. Standard analysis techniques will be used to measure single, double and no labelled surfaces and distances between the two labels of each fluorescence. Standard calculations of the bone formation rate/bone surface (um3/um2/year) will be made.

Outcome measures

Measure	Study Participant n=5 Participants Every study participant will receive etelcalcetide prescribed by their treating physician for the duration of the study. Etelcalcetide: Administered intravenously at the end of each dialysis session. Dosing ranges from 5 mg to 15 mg set by the patient's physician.
Change in Bone Formation Rate	-84 percentage of change Standard Error 17

Adverse Events

Study Participant

Serious events: 3 serious events

Other events: 2 other events

Deaths: 2 deaths

Serious adverse events

Measure	Study Participant n=22 participants at risk Every study participant will receive etelcalcetide prescribed by their treating physician for the duration of the study. Etelcalcetide: Administered intravenously at the end of each dialysis session. Dosing ranges from 5 mg to 15 mg set by the patient's physician.
Infections and infestations COVID-19 infection	4.5% 1/22 • Number of events 1 • 9 months after baseline
Cardiac disorders Cardiac Event	4.5% 1/22 • Number of events 1 • 9 months after baseline
General disorders Vertigo/Dizziness	4.5% 1/22 • Number of events 1 • 9 months after baseline

Other adverse events

Measure	Study Participant n=22 participants at risk Every study participant will receive etelcalcetide prescribed by their treating physician for the duration of the study. Etelcalcetide: Administered intravenously at the end of each dialysis session. Dosing ranges from 5 mg to 15 mg set by the patient's physician.
Infections and infestations Cold Sores	4.5% 1/22 • Number of events 1 • 9 months after baseline
Gastrointestinal disorders Gastrointestinal Disorder	4.5% 1/22 • Number of events 1 • 9 months after baseline

Additional Information

Thomas L.Nickolas, MD, MS

Columbia University

Phone: 212-305-9847

Email: tln2001@cumc.columbia.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place