A Phase 3 Study of Etelcalcetide in Children With Secondary Hyperparathyroidism Receiving Hemodialysis

Phase 3, Single-arm, Open-label, Multidose, Titration, Pharmacokinetic, Pharmacodynamic, and Safety Study of Etelcalcetide in Children and Adolescents ≥ 2 to < 18 Years of Age With Secondary Hyperparathyroidism and Chronic Kidney Disease Receiving Maintenance Hemodialysis

Assess the efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of etelcalcetide in the treatment of secondary hyperparathyroidism (SHPT) in pediatric subjects between ≥ 2 to < 18 years of age, with chronic kidney disease (CKD) on hemodialysis

Study Overview

• Status: Recruiting
• Conditions: Secondary Hyperparathyroidism
• Intervention / Treatment: Drug: Etelcalcetide

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Recruiting
    • Universitair Ziekenhuis Gent
• Czechia
  • Praha 5, Czechia, 150 06
    • Recruiting
    • Fakultni nemocnice v Motole
• France
  • Bron cedex, France, 69677
    • Terminated
    • Hospices Civils de Lyon Hopital Femme Mere Enfant
  • Paris, France, 75012
    • Completed
    • Hôpital Armand Trousseau
• Germany
  • Bonn, Germany, 53127
    • Recruiting
    • Kindernierenzentrum Bonn
  • Hamburg, Germany, 20246
    • Recruiting
    • Universitaetsklinikum Hamburg Eppendorf
  • Hannover, Germany, 30625
    • Completed
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany, 69120
    • Recruiting
    • Universitaetsklinikum Heidelberg, Zentrum fuer Kinder und Jugendmedizin
  • Koeln, Germany, 50937
    • Recruiting
    • Universitaetsklinikum Koeln
• Greece
  • Athens, Greece, 11527
    • Recruiting
    • General Children Hospital Panagioti and Aglaias Kyriakou
  • Thessaloniki, Greece, 54642
    • Recruiting
    • Ippokrateio General Hospital of Thessaloniki
• Hungary
  • Budapest, Hungary, 1083
    • Terminated
    • Semmelweis Egyetem
  • Szeged, Hungary, 6720
    • Terminated
    • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Altalanos Orvostudomanyi Kar
• Italy
  • Firenze, Italy, 50139
    • Recruiting
    • Azienda ospedaliera universitaria Meyer
• Lithuania
  • Vilinus, Lithuania, 08406
    • Terminated
    • Childrens Hospital, Affiliate of Vilnius University Hospital Santaros Klinikos
• Poland
  • Krakow, Poland, 30-663
    • Recruiting
    • Uniwersytecki Szpital Dziecięcy w Krakowie
• Portugal
  • Porto, Portugal, 4050-651
    • Recruiting
    • Unidade Local de Saude de Santo Antonio, EPE - Hospital de Santo Antonio
• Spain
  • Andalucía
    • Sevilla, Andalucía, Spain, 41013
      • Recruiting
      • Hospital Universitario Virgen del Rocío
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Recruiting
      • Hospital Universitari Vall d Hebron
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Recruiting
    • Royal Hospital for Sick Children
  • London, United Kingdom, WC1N 3JH
    • Terminated
    • Great Ormond Street Hospital for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject's legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated.
• Male or female subjects greater than or equal to 2 to less than 18 years of age at the time of enrollment.
• Targeted Dry weight greater than or equal to 7 kg at the time of screening Week -1.
• Diagnosed with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT) undergoing hemodialysis/hemodiafiltration three times per week (TIW) at the time of screening greater than or equal to 1 month.
• Diagnosis of secondary hyperparathyroidism (SHPT) with the mean of the 2 consecutive central laboratory intact parathyroid hormone (iPTH) values greater than 300 pg/mL during screening, on separate days and within 2 weeks of enrollment obtained from the central laboratory during screening.
• Serum corrected calcium (cCa) value greater than or equal to 9.0 mg/dL obtained from the central laboratory during screening.
• Dialysate calcium (Ca) level greater than or equal to 2.5 mEq/L for at least 1 month prior to screening and throughout the duration of the study.
• Subject receiving active vitamin D sterols must have had no more than a maximum dose change of 50% within the 2 weeks prior to screening laboratory assessments, remain stable through enrollment, and be expected to maintain stable doses for the duration of the study, except for adjustments allowed per protocol.
• Subject 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 enrollment, and be expected to maintain stable dose for the duration of the study, except for adjustments allowed per protocol.
• Subject receiving calcium (Ca) supplements must have had no more than a maximum dose change of 50% within the 2 weeks prior to screening laboratory assessments, remain stable through enrollment, and be expected to maintain stable dose for the duration of the study, except for adjustments allowed per protocol.
• Secondary hyperparathyroidism (SHPT) not due to vitamin D deficiency, per investigator assessment.

Exclusion Criteria:

• Disease Related:
• History of congenital long QT syndrome, second or third degree heart block, ventricular tachyarrhythmia's, history of symptomatic ventricular dysrhythmias Torsades de Pointes or other conditions associated with prolonged QT interval.
• Anticipated or scheduled parathyroidectomy during the study period.
• Anticipated or scheduled kidney transplant during the study period.
• Subject has received a parathyroidectomy within 6 months prior to enrollment.
• Other Medical Conditions:
• Current malignancy or history of other malignancy, except non-melanoma skin cancers within the last 5 years.
• Prior/Concomitant Therapy:
• Use of concomitant medications that may prolong the QTc (eg, ondansetron, albuterol, sotalol, amiodarone, erythromycin, or clarithromycin). Refer to CredibleMeds.org for guidance.
• Receipt of cinacalcet therapy within 30 days prior to screening and through enrollment.
• Receipt of etelcalcetide therapy within 6 months prior to screening and through enrollment.
• All herbal medicines (eg, St. John's wort), vitamins, and supplements consumed by the subject within the 30 days prior to enrollment, and continuing use if applicable, will be reviewed by the Principal Investigator and the Amgen Medical Monitor. Written documentation of the review and Amgen acknowledgment is required for subject participation.
• Use of any over-the-counter or prescription medications within the 14 days or 5 half-lives (whichever is longer) prior to enrollment that are not established therapies for subjects with renal disease or other conditions secondary to renal disease will be reviewed by the Principal Investigator and the Amgen Medical Monitor. Written documentation of the review and Amgen acknowledgment is required for subject participation. Paracetamol for analgesia will be allowed.
• Prior/Concurrent Clinical Study Experience:
• Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
• Diagnostic Assessments During Screening:
• Subject has significant abnormalities on the most recent central laboratory test during the screening period prior to enrollment per the Investigator including but not limited to the following: a. Serum transaminase (alanine aminotransferase [ALT] or serum glutamic pyruvic transaminase [SGPT], aspartate aminotransferase [AST], or serum glutamic oxaloacetic transaminase [SGOT]) greater than 1.5 times the upper limit of normal (ULN).
• Corrected QT interval greater than 500 ms, using Bazett's formula.
• Corrected QT interval greater than or equal to 450 to less than or equal to 500 ms, using Bazett's formula, unless written permission to enroll is provided by the investigator after consultation with a pediatric cardiologist.
• Subject has a clinically significant electrocardiogram (ECG) abnormality (eg, unstable arrhythmia) during screening that, in the opinion of the investigator, could pose a risk to subject safety or interfere with the study evaluation.
• Within the 3 Months Prior to Screening:
• New onset or worsening of a pre-existing seizure disorder.
• Subjects on anti-convulsant medication must be on a stable and therapeutic dose for 3 months prior to screening (if blood level monitoring is clinically available, then the subject must have a therapeutic blood level within 1 week of enrollment).

Other Exclusions:

• Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 3 months after the last dose of etelcalcetide. (Females of childbearing potential should only be included in the study after a confirmed menstrual period and a negative highly sensitive serum pregnancy test within 7 days prior to the first dose of investigational product).
• Female subjects of childbearing potential unwilling to use 1 highly effective or acceptable method of effective contraception during treatment and for an additional 3 months after the last dose of investigational product. Refer to Appendix 5 for additional contraceptive information.
• Female subjects of childbearing potential with a positive pregnancy test assessed at screening by a serum pregnancy test.
• Subject has known sensitivity to etelcalcetide or excipients to be administered during dosing.
• Subject 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 subject and investigator's knowledge.
• History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) or unacceptable physical findings, that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation procedures or completion.
• Subject previously has entered this study or previously received treatment with etelcalcetide.
• Anemia, which in the opinion of the investigator makes it not advisable to undergo sequential blood draws.
• History of unstable chronic heart failure within the last 1 year prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Etelcalcetide; Patients will receive etelcalcetide in addition to standard of care

Drug: Etelcalcetide; Etelcalcetide has been shown to be safe and efficacious in treating adult chronic kidney disease (CKD) patients with secondary hyperparathyroidism (SHPT) by simultaneously controlling intact parathyroid hormone (iPTH), calcium (Ca), and phosphorus and has recently been approved for use in adult patients with secondary hyperparathyroidism (SHPT) treated with hemodialysis in both the United States and Europe; Other Names: Parsabiv - brand name

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in intact parathyroid hormone (iPTH) from baseline during the efficacy assessment period (EAP) at weeks 20 to 26	To evaluate the efficacy of etelcalcetide in reducing the intact parathyroid hormone (iPTH) level in children ages equal to or greater than 2 to less than 18 years with secondary hyperparathyroidism (SHPT) receiving maintenance hemodialysis	20 to 26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of a greater than 30% reduction from baseline in mean intact parathyroid hormone (iPTH) during the efficacy assessment period (EAP)	To evaluate the efficacy of etelcalcetide	20 to 26 weeks
Percent change from baseline in corrected total serum calcium (Ca) and serum phosphorus from baseline during the EAP	To characterize change in laboratory markers of chronic kidney disease	20 to 26 weeks
Proportion of subjects achieving corrected serum calcium (Ca) levels less than 8.0 mg/dL (2.0 mmol/L) at any time during the study	To characterize the safety of etelcalcetide treatment based on laboratory values	During the treatment period
Proportion of subjects with hypocalcemia (corrected serum calcium levels less than 8.4 mg/dL)	To characterize the safety of etelcalcetide treatment based on laboratory values	During the treatment period
Etelcalcetide plasma concentrations before and at the end of dialysis after single and multiple doses	Etelcalcetide plasma concentrations before and at the end of dialysis after single and multiple doses	During the treatment period
Etelcalcetide PK parameter of maximum-observed concentration (Cmax)	Etelcalcetide plasma concentrations before and at the end of dialysis after single and multiple doses	During the treatment period
Etelcalcetide pharmacokinetic (PK) parameter of plasma trough concentrations (Cmin)	To characterize the pharmacokinetic (PK) of etelcalcetide treatment after single and multiple doses	During the treatment period
Subject incidence of all treatment-emergent adverse events	To characterize the safety of etelcalcetide treatment based on adverse events. Nature, frequency, severity, and relationship to treatment of all adverse events, including those of special interest reported during the study	During the treatment period

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2019
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: May 29, 2019
• First Submitted That Met QC Criteria: May 29, 2019
• First Posted (Actual): May 31, 2019

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Paediatric; Chronic kidney disease (CKD); Secondary hyperparathyroidism (sHPT)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Parathyroid Diseases; Neoplastic Processes; Hyperparathyroidism; Neoplasm Metastasis; Hyperparathyroidism, Secondary
• Other Study ID Numbers: 20170724

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities.There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes