Etelcalcetide for Secondary Hyperparathyroidism

Recruiting at 44 trial locations

Overseen By Amgen Call Center

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Amgen

Must not be taking: QT prolonging drugs, Cinacalcet

Disqualifiers: Congenital long QT, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 20

Duration: 30 weeks

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called etelcalcetide for children with secondary hyperparathyroidism, a condition where the parathyroid glands produce too much hormone, who also have chronic kidney disease and are on hemodialysis. The goal is to determine if etelcalcetide can manage this condition more effectively than current treatments. Participants will receive either etelcalcetide in addition to their usual care or just their usual care. Children who have been on hemodialysis, have a specific hormone level due to their condition, and do not have other complex heart or cancer issues might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol requires that any over-the-counter or prescription medications not established for renal disease be reviewed by the Principal Investigator and Amgen Medical Monitor. Some medications, like cinacalcet and etelcalcetide, must be stopped before joining the trial. Herbal medicines, vitamins, and supplements also need review and approval.

Is there any evidence suggesting that etelcalcetide is likely to be safe for humans?

Research has shown that etelcalcetide is generally safe and well-tolerated for people with secondary hyperparathyroidism. This condition arises when the parathyroid glands in the neck produce too much hormone due to low calcium levels, often because of kidney disease. In past studies, patients taking etelcalcetide did not encounter any new safety issues over a year of treatment, indicating that the treatment remains stable and manageable over time.

Some reports linked the drug to bleeding in the digestive tract, but these instances were uncommon. Overall, most patients managed the treatment well. The FDA has already approved the drug for treating similar conditions in adults, which provides some confidence in its safety. However, like any medication, side effects can occur, so participants should discuss potential risks with their doctors. ^{1 2 3 4}

Why do researchers think this study treatment might be promising?

Etelcalcetide is unique because it offers a new approach to treating secondary hyperparathyroidism by acting as a calcimimetic. While most standard treatments focus on managing calcium and phosphate levels through dietary changes, vitamin D supplements, or phosphate binders, etelcalcetide directly targets the calcium-sensing receptors in the parathyroid glands, helping to reduce parathyroid hormone levels more effectively. Researchers are excited about this treatment because it can be administered intravenously, potentially providing more consistent results and improved patient compliance compared to oral medications.

What evidence suggests that etelcalcetide might be an effective treatment for secondary hyperparathyroidism?

Research has shown that etelcalcetide, which participants in this trial may receive, effectively treats secondary hyperparathyroidism in patients undergoing hemodialysis. This treatment significantly lowers parathyroid hormone (PTH) levels, crucial because high PTH can cause bone and mineral problems. One study found that about one-third of patients experienced a drop in PTH levels by week 4, with this number nearly doubling by week 8. Another study confirmed that the benefits of etelcalcetide last for a year without new safety concerns. Overall, etelcalcetide effectively manages the main issues related to this condition. ^{1 2 4 5 6}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

This trial is for children under 18 with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT), who are on hemodialysis. They must weigh at least 7 kg, have specific levels of parathyroid hormone and calcium, and not be due to vitamin D deficiency. Kids can't join if they've had certain cancers, used etelcalcetide recently, or are taking conflicting medications.

Inclusion Criteria

You have had high levels of calcium in your dialysis fluid for at least 4 weeks before screening and during the study.

My SHPT is not caused by a lack of vitamin D.

My vitamin D, phosphate binder, or calcium supplement dose hasn't changed by more than 50% in the last 2 weeks.

Exclusion Criteria

Your recent blood tests show high levels of certain liver enzymes, which may indicate liver problems.

I have been taking cinacalcet for the last 30 days and will continue through the study.

Subject has known sensitivity to etelcalcetide or excipients to be administered during dosing

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive etelcalcetide in addition to standard of care or standard of care alone for up to 30 weeks

30 weeks

Regular visits as per hemodialysis schedule

Efficacy Assessment Phase (EAP)

Assessment of efficacy with a focus on iPTH reduction during weeks 20 through 27

7 weeks

Visits during weeks 20 to 27

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Etelcalcetide

Trial Overview The study tests Etelcalcetide's effectiveness in treating SHPT in kids with CKD on hemodialysis. It's a Phase 3 trial which means it’s closer to potentially being approved for general use if successful.

How Is the Trial Designed?

Group I: Etelcalcetide Experimental Treatment 1 Intervention

Randomized in a 3:1 ratio to receive etelcalcetide in addition to standard of care

Group II: Control Active Control 1 Intervention

Randomized in a 3:1 ratio to receive etelcalcetide in addition standard of care alone (control arm)

Etelcalcetide is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Parsabiv for:

• Secondary hyperparathyroidism in adult patients with chronic kidney disease on hemodialysis

Approved in United States as Parsabiv for:

• Secondary hyperparathyroidism in adult patients with chronic kidney disease on hemodialysis

Approved in Japan as Parsabiv for:

• Secondary hyperparathyroidism in adult patients with chronic kidney disease on hemodialysis

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

Etelcalcetide (Parsabiv™) is an innovative calcimimetic agent that effectively lowers parathyroid hormone and calcium levels by targeting the calcium-sensing receptor, making it a promising treatment for secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD).

The drug has received approval in the EU for use in adult patients undergoing haemodialysis for SHPT, with additional regulatory reviews ongoing in the USA and Japan, indicating its potential for widespread clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etelcalcetide: First Global Approval. Blair, HA.[2019]

Etelcalcetide directly suppresses parathyroid hormone secretion in vitro from human parathyroid cells, demonstrating its potential mechanism of action in treating secondary hyperparathyroidism.

In cultures from patients with primary hyperparathyroidism, etelcalcetide showed effective concentrations as low as 0.42 µmol/L, indicating its potency in reducing hormone levels, although further studies are needed to confirm these findings in secondary hyperparathyroidism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of etelcalcetide on parathyroid hormone secretion by primary hyperparathyroidism patient-derived primary parathyroid cells. Fujioka, A., Imanishi, Y., Kobayashi, I., et al.[2021]

Etelcalcetide (Parsabiv) is an effective treatment for managing hyperparathyroidism in adults with chronic kidney disease who are undergoing hemodialysis.

The medication works by mimicking the action of calcium on tissues, helping to lower parathyroid hormone levels and improve calcium balance in patients with kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etelcalcetide (Parsabiv) for Secondary Hyperparathyroidism in Adults With Chronic Kidney Disease on Hemodialysis. Patel, J., Bridgeman, MB.[2023]

In a post-marketing surveillance study of 1226 patients with secondary hyperparathyroidism on dialysis in Japan, etelcalcetide demonstrated significant efficacy, with the percentage of patients achieving target iPTH levels increasing from 19.5% at the start to 64.1% after 52 weeks.

The safety profile of etelcalcetide was consistent with previous findings, with 14.1% of patients experiencing adverse drug reactions, primarily related to metabolism and nutrition, but no new safety concerns were identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of etelcalcetide, an intravenous calcimimetic, for up to 52 weeks in hemodialysis patients with secondary hyperparathyroidism: results of a post-marketing surveillance in Japan. Yokoyama, K., Fukagawa, M., Shigematsu, T., et al.[2021]

Etelcalcetide hydrochloride is the first intravenous calcimimetic agent approved for treating secondary hyperparathyroidism in chronic kidney disease patients, demonstrating its efficacy in lowering parathyroid hormone (PTH) and calcium levels.

In a rat model of chronic renal insufficiency, etelcalcetide effectively decreased plasma PTH and serum calcium levels after a single intravenous dose, confirming its mechanism of action as an allosteric modulator of the calcium-sensing receptor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology of Parsabiv&#174; (etelcalcetide, ONO-5163/AMG 416), a novel allosteric modulator of the calcium-sensing receptor, for secondary hyperparathyroidism in hemodialysis patients. Harada, K., Fujioka, A., Konno, M., et al.[2019]

In a real-world study involving 1,190 dialysis patients, etelcalcetide effectively reduced parathyroid hormone (PTH) levels from a median of 636 pg/mL to 357 pg/mL, with a response rate increasing from 27% to 63% over time.

Etelcalcetide demonstrated a significantly lower incidence of side effects (3-4%) compared to cinacalcet (53%), suggesting it may improve patient adherence to treatment for secondary hyperparathyroidism (SHPT) with less pill burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etelcalcetide in Patients on Hemodialysis with Severe Secondary Hyperparathyroidism. Multicenter Study in "Real Life". Russo, D., Tripepi, R., Malberti, F., et al.[2020]

Etelcalcetide, a novel calcium-sensing receptor agonist, effectively reduced serum intact parathyroid hormone (iPTH) levels in Japanese hemodialysis patients, showing a significant decrease within 30 minutes of administration and sustained effects over multiple doses.

The drug also caused a gradual and sustained decrease in serum calcium levels, indicating its potential efficacy in managing secondary hyperparathyroidism in hemodialysis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single- and Multiple-Dose, Multicenter Study of Etelcalcetide in Japanese Hemodialysis Patients With Secondary Hyperparathyroidism. Yokoyama, K., Fukagawa, M., Shigematsu, T., et al.[2022]

Citations

1. parsabivhcp.com parsabivhcp.com/efficacy

Efficacy - Parsabiv® (etelcalcetide) One-third of patients given Parsabiv® had a reduction in PTH by week 4*—and by week 8 that number nearly doubled · Post-hoc analysis: Time to first occurrence* ...

2. clinicaltrials.gov clinicaltrials.gov/ct2/show/nct01785849

Efficacy and Safety of Etelcalcetide (AMG 416) in the ... Failure to submit primary and secondary outcomes ... Etelcalcetide Is Effective at All Levels of Severity of Secondary Hyperparathyroidism in Hemodialysis ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30859218/

One-year safety and efficacy of intravenous etelcalcetide in ... Conclusions: Etelcalcetide effectively lowered PTH and its effect was sustained, while no new safety concerns emerged over a 1-year treatment ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0211699524000900

Etelcalcetide: What we know eight years since its approval Regarding bone and mineral metabolism, etelcalcetide is effective in reducing serum levels of parathormone (PTH), calcium, phosphate and fibroblast growth ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6027851/

Etelcalcetide (Parsabiv) for Secondary ... The primary efficacy endpoint was the proportion of patients achieving a greater than 30% reduction from baseline mean PTH concentrations during the assessment ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2017/208325Orig1s000MedR.pdf

208325Orig1s000 - accessdata.fda.gov The report summarizes both non-clinical and clinical data regarding a potential association between etelcalcetide and. GIB and evidence ...