Etelcalcetide for Secondary Hyperparathyroidism

Recruiting at 39 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

Trial Summary

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.

What data supports the effectiveness of the drug Etelcalcetide for secondary hyperparathyroidism?

Research shows that Etelcalcetide effectively lowers parathyroid hormone and calcium levels in patients with secondary hyperparathyroidism, especially those on hemodialysis, by targeting the calcium-sensing receptor. ^{1 2 3 4 5}

Is Etelcalcetide safe for humans?

Etelcalcetide has been studied for safety in hemodialysis patients with secondary hyperparathyroidism, showing a safety and tolerability profile in clinical studies and post-marketing surveillance in Japan. ^{1 2 3 4 6}

What makes the drug Etelcalcetide unique for treating secondary hyperparathyroidism?

Etelcalcetide is unique because it is a second-generation calcimimetic (a drug that mimics calcium) that is administered intravenously, which can reduce the burden of taking pills. It directly binds to the calcium-sensing receptor to lower parathyroid hormone levels, and it has fewer side effects compared to other treatments like cinacalcet. ^{1 2 3 6 7}

What is the purpose of this trial?

This is a Phase 3 Study of Etelcalcetide in Pediatric Subjects With Secondary Hyperparathyroidism and Chronic Kidney Disease on Hemodialysis

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Etelcalcetide: First Global Approval. [2019]

2. Japan pubmed.ncbi.nlm.nih.gov

Effect of etelcalcetide on parathyroid hormone secretion by primary hyperparathyroidism patient-derived primary parathyroid cells. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Etelcalcetide (Parsabiv) for Secondary Hyperparathyroidism in Adults With Chronic Kidney Disease on Hemodialysis. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

A Single- and Multiple-Dose, Multicenter Study of Etelcalcetide in Japanese Hemodialysis Patients With Secondary Hyperparathyroidism. [2022]

5. Netherlands 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. [2019]

6. Japan 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. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Etelcalcetide in Patients on Hemodialysis with Severe Secondary Hyperparathyroidism. Multicenter Study in "Real Life". [2020]