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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

4 Oct 2019 → ongoing

Decision date (initial)

2024-01-30

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Amgen Inc.

External identifiers

EU CT number

2023-506471-10-00

EudraCT number

2018-004608-21

WHO UTN

U1111-1296-0784

ClinicalTrials.gov

NCT03969329

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of etelcalcetide in reducing the intact parathyroid hormone (IPTH) level in children ages ≥ 2 to <18 years with secondary hyperparathyroidism (SHPT) receiving maintenance hemodialysis

Secondary objectives 4

1. To evaluate the efficacy of etelcalcetie in reducing the IPTH level by > 30%
2. To characterize change in laboratory markers of chronic Kidney disease (CKD) following etelcalcetide treatment
3. To characterize the safety of etelcalcetide treatment based on laboratory values
4. To characterize the pharmacokinetic (PK) of etelcalcetide treatment after single and multiple doses

Conditions and MedDRA coding

Secondary hyperparathyroidism (SHPT) in pediatric patients with chronic kidney disease (CKD) in hemodialysis

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Swedish Medical Products Agency, Austrian Agency For Health And Food Safety

EMA paediatric investigation plan (PIP)

EMEA-001554-PIP01-13

Plan to share 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 Information on IPD sharing Access Criteria, Time Frame and Supporting Information Type is available on ClinicalTrials.gov (https://clinicaltrials.gov/study/NCT03969329?term=20170724&rank=1) and on the Amgen Clinical Trials portal (http://www.amgen.com/datasharing).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 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
2. 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
3. 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
4. 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
5. SHPT not due to vitamin D deficiency, per investigator assessment
6. Male or female subjects ≥ 2 to < 18 years of age at the time of enrollment
7. Targeted dry weight ≥ 7 kg at the time of screening Week -1
8. Diagnosed with CKD and SHPT undergoing hemodialysis/hemodiafiltration TIW or QIW at the time of screening ≥ 1 month
9. 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
10. Serum cCa value ≥9.0 mg/dL obtained from the central laboratory during screening
11. Dialysate Ca level ≥ 2.5 mEq/L for at least 1 month prior to screening and throughout the duration of the study

Exclusion criteria 28

1. 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
2. Anemia, which in the opinion of the investigator makes it not advisable to undergo sequential blood draws
3. History of unstable chronic heart failure within the last 1 year prior to screening
4. 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
5. Anticipated or scheduled kidney transplant during the study period
6. Subject has received a parathyroidectomy within 6 months prior to enrollment
7. Current malignancy or history of other malignancy, except non-melanoma skin cancers within the last 5 years
8. 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.
9. Receipt of cinacalcet therapy within 30 days prior to screening and through enrollment
10. Receipt of etelcalcetide therapy within 6 months prior to screening assessments and through enrollment (Amendment 3 and later only).
11. 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
12. 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).
13. Any previous use of etelcalcetide prior to screening and through enrollment (Original protocol, Amendment 1, and Amendment 2 only).
14. 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
15. Subject has previously entered this study (Amendment 3 and later only).
16. 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)
17. Corrected QT interval > 500 ms, using Bazett’s formula
18. 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
19. 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
20. New onset or worsening of a pre-existing seizure disorder
21. 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
22. 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)
23. Anticipated or scheduled parathyroidectomy during the study period
24. Female subjects of childbearing potential with a positive pregnancy test assessed at screening by a serum pregnancy test
25. Subject has known sensitivity to etelcalcetide or excipients to be administered during dosing
26. 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
27. 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
28. Subject has previously entered this study or previously received treatment with etelcalcetide (Original protocol, Amendment 1 and Amendment 2 only).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change in IPTH from baseline during the efficacy assessment period (EAP) at weeks 20 to 26

Secondary endpoints 7

1. Achievement of a > 30% reduction from baseline in mean IPTH during the EAP
2. Percent change from baseline in corrected total serum calcium (Ca) and serum phosphorus from baseline during the EAP
3. Occurence of corrected serum Ca levels <8.0 mg/dL (2.0 mmol/L) any time during the study
4. Changes in laboratory parameters, incluidng clinical chemistry
5. Occurence of hypocalcemia (corrected serum Ca levels <8.4 mg/dL)
6. Etelcalcetide plasma concentrations before and at the end of dialysis after single and multiple doses
7. Etelcalcetide PK parameters including, but not limited to, maximum plasma concentration ( Cmax) and plasma trough concentrations (Cmin)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1799

Country

United States

Scientific contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Public contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Third parties 4

Locations

8 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 60 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications