The Effect of Etelcalcetide on CKD-MBD
Condition: Chronic Kidney Disease Mineral and Bone Disorder; Renal Osteodystrophy; Vascular Calcification; Hyperparathyroidism; Secondary, Renal
MeSH terms: Bone Diseases; Chronic Kidney Disease-Mineral and Bone Disorder; Kidney Diseases; Renal Insufficiency, Chronic; Calcinosis; Vascular Calcification; Hyperparathyroidism; Hyperparathyroidism, Secondary
Intervention: Etelcalcetide
Intervention description: Administered intravenously at the end of each dialysis session. Dosing ranges from 5 mg to 15 mg set by the patient's physician.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Kidney disease; Bone disease; Etelcalcetide; Parsabiv

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.
    

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.