Chronic Kidney Disease Mineral and Bone DisorderPhase 2Parsabiv-MBDNCT03960437
The Effect of Etelcalcetide on CKD-MBD
A Phase 2 study testing Etelcalcetide in people with Chronic Kidney Disease Mineral and Bone Disorder and Renal Osteodystrophy, run by Thomas Nickolas, MD MS at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Kidney Disease Mineral and Bone Disorder, Renal Osteodystrophy, Vascular Calcification
- What is being tested?
- Etelcalcetide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Sep 2018to 19 Nov 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- 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*.
- 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*.
- The treating physician considers the etelcalcetide dose and timing points described in this protocol as acceptable/optimal for their patient.
- 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
Who cannot join
- 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.
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- 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.
- Weight >300 pounds
- For Aim 1 (Bone biopsy):
- 1. Allergy to tetracycline or demeclocycline.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Irving Medical Center
New York, New York, 10032
About this study
Official title: The Effect of Etelcalcetide on Bone-tissue Properties and Calcification Propensity in End Stage Kidney Disease
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.
Read the 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
- Being tested
- Etelcalcetide
- Keywords
- Kidney disease, Bone disease, Etelcalcetide, Parsabiv
- Medical subject headings
- Chronic Kidney Disease-Mineral and Bone Disorder, Vascular Calcification, Hyperparathyroidism, Neoplasm Metastasis, Kidney Diseases, Bone Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtelcalcetideDrug
Also called Parsabiv
Administered intravenously at the end of each dialysis session. Dosing ranges from 5 mg to 15 mg set by the patient's physician.
| Study group | Role | What they receive |
|---|---|---|
| Study Participant | Other | Every study participant will receive etelcalcetide prescribed by their treating physician for the duration of the study. Receives: Drug: Etelcalcetide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in PTH Levels
Mean percent change in parathyroid hormone (PTH) levels will be calculated.
Measured: 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.
Measured: 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.
Measured: 9 months
Percent Change in Mean Hardness
Hardness will be measured by Ramen nano-indentation and mineralization measured by histomorphometry obtained (in GPa).
Measured: Baseline and 9 months
Secondary outcomes (3)
Change in Bone Mineral Density (BMD) of the Spine by DXA
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.
Measured: Baseline and 9 months
Change in Bone Mineral Density (BMD) of Total Hip by DXA
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.
Measured: Baseline and 9 months
Change in Bone Formation Rate
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.
Measured: Baseline and 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2019
- Study start6 Sep 2018
- Primary completion19 Nov 2020
- Study completion19 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Kidney Disease Mineral and Bone DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Nickolas, MD MS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Thomas Nickolas, MD MS, Columbia University
- Investigators
- Thomas Nickolas, MD, MS, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03960437
- Sponsor's protocol ID
- AAAR6244
- Acronym
- Parsabiv-MBD
- Status last verified
- Aug 2023
- First submitted
- 21 May 2019
- Last updated
- 21 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 37574661
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Etelcalcetide on Bone-tissue Properties and Calcification Propensity in End Stage Kidney Disease
- ClinicalTrials.gov ID
- NCT03960437
- Acronym / sponsor ID
- Parsabiv-MBD / AAAR6244
- Conditions
- Chronic Kidney Disease Mineral and Bone Disorder, Renal Osteodystrophy, Vascular Calcification, Hyperparathyroidism; Secondary, Renal
- Keywords
- Kidney disease, Bone disease, Etelcalcetide, Parsabiv
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Thomas Nickolas, MD MSUniversity, hospital or other
- Study start
- 6 Sep 2018 (actual)
- Primary completion
- 19 Nov 2020 (actual)
- Study completion
- 19 Nov 2020 (actual)
- First posted
- 23 May 2019 (actual)
- Results
- Posted 21 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study Participant | Other | Drug: EtelcalcetideEvery study participant will receive etelcalcetide prescribed by their treating physician for the duration of the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EtelcalcetideAlso: ParsabivAdministered intravenously at the end of each dialysis session. Dosing ranges from 5 mg to 15 mg set by the patient's physician. | Drug | Study Participant |
Primary outcome
Percent Change in PTH Levels
Time frame: Baseline and 9 months
Mean percent change in parathyroid hormone (PTH) levels will be calculated.
Change in Bone Mineral Density (BMD) of the Femoral Neck by Dual-energy X-ray Absorptiometry (DXA)
Time frame: Baseline and 9 months
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.
Propensity as Measured by T50
Time frame: 9 months
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.
Percent Change in Mean Hardness
Time frame: Baseline and 9 months
Hardness will be measured by Ramen nano-indentation and mineralization measured by histomorphometry obtained (in GPa).
3 secondary outcomes
Change in Bone Mineral Density (BMD) of the Spine by DXA
Time frame: Baseline and 9 months
Change in Bone Mineral Density (BMD) of Total Hip by DXA
Time frame: Baseline and 9 months
Change in Bone Formation Rate
Time frame: Baseline and 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37574661Khairallah 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Nickolas, MD, MS principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Etelcalcetide in people with Chronic Kidney Disease Mineral and Bone Disorder and Renal Osteodystrophy, run by Thomas Nickolas, MD MS at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in PTH Levels (time frame: Baseline and 9 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03960437, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2023.