ETELCALCETIDE for Secondary hyperparathyroidism (secondary hyperparathyroidism, SHPT)|Chronic kidney disease on maintenance hemodialysis (Chronic kidney disease, CKD, on hemodialysis)

Inclusion criteria

• {"criterion_text":"- 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\n- Serum cCa value ≥9.0 mg/dL obtained from the central laboratory during screening\n- Dialysate Ca level ≥ 2.5 mEq/L for at least 1 month prior to screening and throughout the duration of the study\n- 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\n- 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\n- Subject receiving 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\n- SHPT not due to vitamin D deficiency, per investigator assessment\n- Male or female subjects ≥ 2 to < 18 years of age at the time of enrollment\n- Targeted dry weight ≥ 7 kg at the time of screening Week -1\n- Diagnosed with CKD and SHPT undergoing hemodialysis/hemodiafiltration TIW or QIW at the time of screening ≥ 1 month\n- Diagnosis of SHPT with the mean of the 2 consecutive central laboratory iPTH values > 300 pg/mL during screening, on separate days and within 2 weeks of enrollment obtained from the central laboratory during screening"}

Exclusion criteria

• {"criterion_text":"- 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\n- Receipt of etelcalcetide therapy within 6 months prior to screening assessments and through enrollment (Amendment 3 and later only).\n- 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\n- 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).\n- Any previous use of etelcalcetide prior to screening and through enrollment (Original protocol, Amendment 1, and Amendment 2 only).\n- 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\n- Subject has previously entered this study (Amendment 3 and later only).\n- 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]) > 1.5 times the upper limit of normal (ULN)\n- Corrected QT interval > 500 ms, using Bazett’s formula\n- Corrected QT interval ≥ 450 to ≤ 500 ms, using Bazett’s formula, unless written permission to enroll is provided by the investigator after consultation with a pediatric cardiologist\n- 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\n- Anemia, which in the opinion of the investigator makes it not advisable to undergo sequential blood draws\n- New onset or worsening of a pre-existing seizure disorder\n- 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\n- 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)\n- Anticipated or scheduled parathyroidectomy during the study period\n- Female subjects of childbearing potential with a positive pregnancy test assessed at screening by a serum pregnancy test\n- Subject has known sensitivity to etelcalcetide or excipients to be administered during dosing\n- 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\n- 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\n- Subject has previously entered this study or previously received treatment with etelcalcetide (Original protocol, Amendment 1 and Amendment 2 only).\n- History of unstable chronic heart failure within the last 1 year prior to screening\n- 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\n- Anticipated or scheduled kidney transplant during the study period\n- Subject has received a parathyroidectomy within 6 months prior to enrollment\n- Current malignancy or history of other malignancy, except non-melanoma skin cancers within the last 5 years\n- Use of concomitant medications that may prolong the QTc (eg, ondansetron, albuterol, sotalol, amiodarone, erythromycin, or clarithromycin). Refer to CredibleMeds.org for guidance. Certain medications may be allowed based on review by the medical monitor and require additional ECG monitoring and potential electrolyte monitoring.\n- Receipt of cinacalcet therapy within 30 days prior to screening and through enrollment"}

Primary endpoints

• {"endpoint_text":"- Percent change in IPTH from baseline during the efficacy assessment period (EAP) at weeks 20 to 26","definition_or_measurement_approach":"Measured as percent change in intact parathyroid hormone (iPTH) from baseline using central laboratory iPTH values during the efficacy assessment period (EAP) at weeks 20–26."}

Secondary endpoints

• {"endpoint_text":"- Achievement of a > 30% reduction from baseline in mean IPTH during the EAP","definition_or_measurement_approach":"Proportion of subjects achieving >30% reduction from baseline in mean iPTH during the EAP (central laboratory measurements)."}
• {"endpoint_text":"- Percent change from baseline in corrected total serum calcium (Ca) and serum phosphorus from baseline during the EAP","definition_or_measurement_approach":"Percent change from baseline in corrected total serum calcium and serum phosphorus measured by central laboratory during the EAP."}
• {"endpoint_text":"- Occurence of corrected serum Ca levels <8.0 mg/dL (2.0 mmol/L) any time during the study","definition_or_measurement_approach":"Incidence of corrected serum calcium <8.0 mg/dL (2.0 mmol/L) at any time during the study (laboratory assessment)."}
• {"endpoint_text":"- Changes in laboratory parameters, incluidng clinical chemistry","definition_or_measurement_approach":"Descriptive changes in laboratory parameters including clinical chemistry values (central laboratory assessments)."}
• {"endpoint_text":"- Occurence of hypocalcemia (corrected serum Ca levels <8.4 mg/dL)","definition_or_measurement_approach":"Incidence of corrected serum calcium <8.4 mg/dL during the study."}
• {"endpoint_text":"- Etelcalcetide plasma concentrations before and at the end of dialysis after single and multiple doses","definition_or_measurement_approach":"Plasma concentration measurements of etelcalcetide pre- and post-dialysis after single and multiple doses (PK sampling schedule)."}
• {"endpoint_text":"- Etelcalcetide PK parameters including, but not limited to, maximum plasma concentration ( Cmax) and plasma trough concentrations (Cmin)","definition_or_measurement_approach":"Calculation of PK parameters (e.g., Cmax, Cmin) from plasma concentration–time data collected per protocol."}

Belgium

Earliest CTIS Part Ii Submission Date

11-12-2023

Latest Decision Or Authorization Date

30-01-2024

Processing Time Days

50

Number Of Sites

1

Number Of Participants

1

Italy

Earliest CTIS Part Ii Submission Date

11-12-2023

Latest Decision Or Authorization Date

14-02-2024

Processing Time Days

65

Number Of Sites

1

Number Of Participants

3

Poland

Earliest CTIS Part Ii Submission Date

11-12-2023

Latest Decision Or Authorization Date

29-02-2024

Processing Time Days

80

Number Of Sites

1

Number Of Participants

1

Portugal

Earliest CTIS Part Ii Submission Date

11-12-2023

Latest Decision Or Authorization Date

30-01-2024

Processing Time Days

50

Number Of Sites

1

Number Of Participants

1

Greece

Earliest CTIS Part Ii Submission Date

11-12-2023

Latest Decision Or Authorization Date

04-03-2024

Processing Time Days

84

Number Of Sites

2

Number Of Participants

7

Czechia

Earliest CTIS Part Ii Submission Date

11-12-2023

Latest Decision Or Authorization Date

01-02-2024

Processing Time Days

52

Number Of Sites

1

Number Of Participants

3

Germany

Earliest CTIS Part Ii Submission Date

11-12-2023

Latest Decision Or Authorization Date

31-01-2024

Processing Time Days

51

Number Of Sites

3

Number Of Participants

9

Spain

Earliest CTIS Part Ii Submission Date

11-12-2023

Latest Decision Or Authorization Date

04-03-2024

Processing Time Days

84

Number Of Sites

2

Number Of Participants

1

Primary sponsor

Full Name

Amgen Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Excelya Greece CRO Single Member S.A.

Responsibilities

Monitoring, Submission Activities

Name

Quipment

Responsibilities

Equipment provisioning

Name

Almac Clinical Technologies LLC

Responsibilities

code: 3

Name

Labcorp Central Laboratory Services S.a.r.l.

Responsibilities

code: 4

Third parties

• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"code: 3","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Quipment","duties_or_roles":"Equipment provisioning","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Greece","full_name":"Excelya Greece CRO Single Member S.A.","duties_or_roles":"Monitoring, Submission Activities","organisation_type":"Pharmaceutical company"}