The Effect of Etelcalcetide on CKD-MBD

NCT03960437 | Completed Phase 2 Results FDA Drug

• 1 other identifier: AAAR6244
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Kidney disease; Bone disease; Etelcalcetide; Parsabiv

Outcome Measures

Primary Outcomes (4)

• Percent Change in PTH Levels

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

  Baseline and 9 months

• Change in Bone Mineral Density (BMD) of the Femoral Neck by Dual-energy X-ray Absorptiometry (DXA)

  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.

  Baseline and 9 months

• Propensity as Measured by T50

  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.

  9 months

• Percent Change in Mean Hardness

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

  Baseline and 9 months

Secondary Outcomes (3)

• Change in Bone Mineral Density (BMD) of the Spine by DXA

  Baseline and 9 months

• Change in Bone Mineral Density (BMD) of Total Hip by DXA

  Baseline and 9 months

• Change in Bone Formation Rate

  Baseline and 9 months

Study Arms (1)

Study Participant

OTHER

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

Drug: Etelcalcetide

Interventions

Etelcalcetide DRUG

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

Also known as: Parsabiv

Study Participant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For All Aims:
• Patient has provided informed consent.
• Patient is 18 years of age or older.
• 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.
• Dialysate calcium concentration must be stable for at least 4 weeks prior to screening laboratory assessments.
• 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.
• 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.
• Scheduled to receive etelcalcetide for the treatment of HPT per standard of care.
• 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\*.
• 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.

You may not qualify if:

• For All Aims:
• 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).
• Currently receiving investigational procedures while participating in this study.
• Patient with controlled PTH as defined by KDIGO as a PTH of 2 to 9 times the upper limit of normal of the assay.
• Patients has received a bisphosphonate, denosumab or teriparatide during the 12 months prior to screening.
• Anticipated or scheduled parathyroidectomy during the study period.
• Patient has received a parathyroidectomy within 6 months prior to dosing.
• Scheduled kidney transplant during the study period or anticipated living donor evaluation within three months of recruitment
• 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.
• Bilateral lower extremity amputations or non-ambulatory
• Metabolic bone diseases not related to the kidney (i.e., Pagets, Osteogenesis Imprefecta)
• Untreated hyperthyroidism or hypoparathyroidism
• Malignancy within the last 5 years (except non-melanoma skin cancers or cervical carcinoma in situ).
• Patient is pregnant or nursing.
• 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.

Sponsors & Collaborators

• Thomas Nickolas, MD MS: lead

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Related Publications (1)

• 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.

  PMID: 37574661 DERIVED

MeSH Terms

Conditions

Chronic Kidney Disease-Mineral and Bone Disorder; Vascular Calcification; Hyperparathyroidism; Neoplasm Metastasis; Kidney Diseases; Bone Diseases

Interventions

etelcalcetide hydrochloride

Condition Hierarchy (Ancestors)

Rickets; Bone Diseases, Metabolic; Musculoskeletal Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Calcium Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Hyperparathyroidism, Secondary; Parathyroid Diseases; Endocrine System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Calcinosis; Neoplastic Processes; Neoplasms

Results Point of Contact

• Title: Thomas L.Nickolas, MD, MS
• Organization: Columbia University

tln2001@cumc.columbia.edu

212-305-9847

Study Officials

• Thomas Nickolas, MD, MS

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: May 21, 2019
• First Posted: May 23, 2019
• Study Start: September 6, 2018
• Primary Completion: November 19, 2020
• Study Completion: November 19, 2020
• Last Updated: September 21, 2023
• Results First Posted: September 21, 2023

Record last verified: 2023-08

Locations

US (1)