The Effect of Etelcalcetide on CKD-MBD

NCT ID: NCT03960437

Last Updated: 2023-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-06
• Study Completion Date: 2020-11-19

Brief Summary

The proposed study will investigate the effects of etelcalcetide on the bone and blood-vessel health in patients with CKD-MBD. The investigators will test if etelcalcetide makes bone and blood-vessels healthier. The study hypotheses are that are that etelcalcetide keeps bones strong and lowers the risk of calcium deposits in blood vessels. In Aim 1, the investigators will test if 9-months of treatment with etelcalcetide improves bone strength in twenty ESKD patients with hyperparathyroidism (HPT) by bone biopsy. In Aim 2, the investigators will test if 9-months of treatment with etelcalcetide decreases serum propensity to calcify blood vessels. The potential significance of this study is to provide first-time data on the ability of etelcalcetide to protect bone and blood-vessel health in patients with ESKD.

Detailed Description

Chronic kidney disease - mineral and bone disease (CKD-MBD) is a disorder of bone and mineral metabolism in patients with CKD. When kidney function is poor, levels of vitamin D, phosphate and parathyroid hormone become abnormal and patients are at risk for bone disease and fractures (renal osteodystrophy) and the deposition of calcium in blood vessels and muscles. CKD-MBD increases the risk of fractures, heart attacks, strokes, and death. Treatment of CKD-MBD is focused on lowering levels of parathyroid hormone (PTH) by giving vitamin D and lowering levels of phosphorous by giving phosphate binders. In patients with end stage kidney disease (ESKD), target levels of PTH recommended by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines are in the range of 2-9 times the upper limit of normal (ULN) for the PTH assay. In many cases, in patients with long-standing ESKD, the parathyroid gland may no longer respond to treatment with vitamin D and phosphate lowering. In these cases, treatment with a calcimimetic, a medicine that increases the sensitivity of the parathyroid gland to serum levels of calcium, can restore PTH levels to goal.

Conditions

Chronic Kidney Disease Mineral and Bone Disorder; Renal Osteodystrophy; Vascular Calcification; Hyperparathyroidism; Secondary, Renal

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Study Participant

Every study participant will receive etelcalcetide prescribed by their treating physician for the duration of the study.

Group Type: OTHER

Etelcalcetide

Intervention Type: DRUG

Administered intravenously at the end of each dialysis session. Dosing ranges from 5 mg to 15 mg set by the patient's physician.

Interventions

Etelcalcetide

Administered intravenously at the end of each dialysis session. Dosing ranges from 5 mg to 15 mg set by the patient's physician.

Intervention Type: DRUG

Other Intervention Names

Parsabiv

Eligibility Criteria

Inclusion Criteria

For All Aims:

1. Patient has provided informed consent.

2. Patient is 18 years of age or older.

3. Patient must be receiving maintenance hemodialysis for at least 3 months, with adequate hemodialysis with a delivered Kt/V 1.2 or urea reduction ratio (URR) 65% within 4 weeks prior to screening laboratory assessments.

4. Dialysate calcium concentration must be stable for at least 4 weeks prior to screening laboratory assessments.

5. Patient must have severe HPT as defined by two laboratory screening pre-dialysis serum PTH values >9-times ULN for the PTH assay, measured on two consecutive monthly lab checks prior to entering the study.

6. The patient has an uncontrolled PTH defined by KDIGO as a PTH greater than 9 times the upper limit of normal of the assay (720 pg/mL for Rogosin):

AND one of the following:

• The patient has never been on cinacalcet OR,
• The patient received daily cinacalcet for less than 3 months and has been off cinacalcet for at least 3 months prior to enrollment OR ,
• The patient received daily cinacalcet for more than 3 months and has been off cinacalcet for at least 6 months prior to enrollment OR,
• The patient received a modified dose of three times weekly cinacalcet and has been off cinacalcet for at least one month prior to enrollment.

7. Scheduled to receive etelcalcetide for the treatment of HPT per standard of care.

8. If receiving vitamin D sterols, patient must have had no more than a maximum dose change of 50% within the 4 weeks prior to screening laboratory assessments, remain stable through randomization, and be expected to maintain stable doses for the duration of the study, except for adjustments allowed per protocol*.

9. Patient must have one screening pre-dialysis serum Ca laboratory value at least at the lower limit of normal for the assay measured within 4 weeks prior to entering the study.

10. A patient receiving calcium supplements must have had no more than a maximum dose change of 50% within 2 weeks prior to screening laboratory assessments and remain stable throughout the study, except for adjustments allowed per protocol*.

11. A patient receiving phosphate binders must have had no more than a maximum dose change of 50% within the 2 weeks prior to screening laboratory assessments, remain stable through, and be expected to maintain stable dose for the duration of the study, except for adjustments allowed per protocol*.

12. The treating physician considers the etelcalcetide dose and timing points described in this protocol as acceptable/optimal for their patient.

13. Female patients must be willing to use highly effective contraception during the study and for 3 months after the last dose of etelcalcetide (unless postmenopausal or surgically sterilized).

For Aim 1:

1. Total alkaline phosphatase ≥ the upper tertile of the reference range for the assay

Exclusion Criteria

For All Aims:

1. Currently receiving treatment in an investigational device or drug study, or less than 30 days since ending treatment on an investigational device or drug study(s).

2. Currently receiving investigational procedures while participating in this study.

3. Patient with controlled PTH as defined by KDIGO as a PTH of 2 to 9 times the upper limit of normal of the assay.

4. Patients has received a bisphosphonate, denosumab or teriparatide during the 12 months prior to screening.

5. Anticipated or scheduled parathyroidectomy during the study period.

6. Patient has received a parathyroidectomy within 6 months prior to dosing.

7. Scheduled kidney transplant during the study period or anticipated living donor evaluation within three months of recruitment

8. Patient has an unstable medical condition based on medical history, physical examination, and routine laboratory tests, or is otherwise unstable in the judgment of the Investigator.

9. Bilateral lower extremity amputations or non-ambulatory

10. Metabolic bone diseases not related to the kidney (i.e., Pagets, Osteogenesis Imprefecta)

11. Untreated hyperthyroidism or hypoparathyroidism

12. Malignancy within the last 5 years (except non-melanoma skin cancers or cervical carcinoma in situ).

13. Patient is pregnant or nursing.

14. Patient likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the patient and Investigator's knowledge.

15. Weight >300 pounds

For Aim 1 (Bone biopsy):

1. Allergy to tetracycline or demeclocycline.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Thomas Nickolas, MD MS

OTHER

Sponsor Role: lead

Responsible Party

Thomas Nickolas, MD MS

Associate Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Thomas Nickolas, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Irving Medical Center

New York, New York, United States

Countries

United States

References

Khairallah P, Cherasard J, Sung J, Agarwal S, Aponte MA, Bucovsky M, Fusaro M, Silberzweig J, Frumkin GN, El Hachem K, Schulman L, McMahon D, Allen MR, Metzger CE, Surowiec RK, Wallace J, Nickolas TL. Changes in Bone Quality after Treatment with Etelcalcetide. Clin J Am Soc Nephrol. 2023 Nov 1;18(11):1456-1465. doi: 10.2215/CJN.0000000000000254. Epub 2023 Aug 14.

Reference Type: DERIVED

PMID: 37574661 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

AAAR6244

Identifier Type: -

Identifier Source: org_study_id