Resumen

Este es un ensayo clínico de Fase 3 de etelcalcetida en participantes pediátricos con hiperparatiroidismo secundario (HPTS) y enfermedad renal crónica (ERC) en hemodiálisis.

Descripción detallada

El HPTS es una comorbilidad común y grave que se desarrolla de forma relativamente temprana en el curso de la ERC, empeora con el deterioro de la función renal y está asociado con complicaciones graves en niños en diálisis. Los niños en diálisis experimentan una amplia gama de anomalías óseas y retraso del crecimiento, además de un mayor riesgo de morbilidad y mortalidad cardiovascular que se manifiesta tempranamente en su adultez. Las terapias tradicionales para el HPTS (por ejemplo, esteroles de vitamina D) son ampliamente utilizadas en la población pediátrica en diálisis y tienen el potencial de agravar las complicaciones de la enfermedad al aumentar el calcio sérico (Ca), el fósforo sérico y el producto de Ca sérico por fósforo sérico. Se ha demostrado que etelcalcetida es segura y eficaz para tratar a pacientes adultos con ERC y HPTS, controlando simultáneamente la hormona paratiroidea intacta (iPTH), el Ca y el fósforo, y recientemente ha sido aprobada para uso en pacientes adultos con HPTS tratados con hemodiálisis tanto en Estados Unidos como en Europa. Aunque no se han realizado ensayos clínicos previos en pacientes pediátricos con etelcalcetida (actualmente está en curso un ensayo de farmacocinética [FK] de dosis única), Amgen prevé un riesgo mínimo a moderado con posibilidad de beneficio directo para los participantes pediátricos (de 28 días a 18 años de edad) en este ensayo clínico. La carga de complicaciones del HPTS en la población pediátrica en diálisis y las limitaciones de la terapia estándar actual subrayan la necesidad de realizar ensayos clínicos de etelcalcetida en estos pacientes, a fin de abordar esta necesidad médica no cubierta e informar a la comunidad de nefrología pediátrica sobre el potencial uso de etelcalcetida en niños en hemodiálisis con datos críticos de seguridad y eficacia.

Elegibilidad

Edad mínima: 0 YearsEdad máxima: 18 YearsSexo: ALL

Criterios de inclusión

Age of 28 days \< 18 years.
Dry weight ≥ 7 kg during screening.
Diagnosed with CKD and SHPT undergoing hemodialysis at the time of screening.
Diagnosis of SHPT with the mean of the 2 consecutive central laboratory iPTH values ≥ 300 pg/mL (32 pmol/L) during screening, on separate days and within 2 weeks of enrolment.
Serum corrected calcium (cCa) value ≥ 9.0 mg/dL (2.25 mmol/L) for participants ≥ 2 years of age and older and serum cCa value ≥ 9.6 mg/dL (2.4 mmol/L) for participants 28 days to \< 2 years of age obtained from the central laboratory during screening.
Dialysate Ca level ≥ 2.5 mEq/L during screening for at least 4 weeks prior to screening and throughout the duration of the trial.
No more than a maximum prescribed dose change of 50% for active vitamin D sterols/phosphate binders/Ca supplements within the 2 weeks prior to screening assessments and remain stable.
SHPT not due to vitamin D deficiency, per investigator assessment.

Criterios de exclusión

History of congenital long QT syndrome, second or third degree heart block, ventricular tachyarrhythmia's or other conditions associated with prolonged QT interval.
Anticipated or scheduled parathyroidectomy during the trial period.
Anticipated or scheduled kidney transplant during the trial period.
Participant has received a parathyroidectomy within 6 months prior to randomization.
Other Medical Conditions
• History of other malignancy, except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years.
Prior/Concomitant Therapy
Use of concomitant medications that may prolong the corrected QT interval (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 electrocardiogram (ECG) monitoring and potential electrolyte monitoring.
Receipt of cinacalcet therapy within 30 days prior to screening assessments and through randomization.
Receipt of etelcalcetide within 6 months prior to screening assessments and through randomization.
All herbal medicines (eg, St. John's wort), vitamins, and supplements consumed by the participant within the 30 days prior to randomization, 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 participant participation.
Use of any over-the-counter or prescription medications within the 14 days or 5 half-lives (whichever is longer) prior to randomization that are not established therapies for participants 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 participant participation. Paracetamol for analgesia will be allowed.
Prior/Concurrent Clinical Trial Experience • Currently receiving treatment in another investigational device or drug trial, or less than 30 days or 5 half-lives (whichever is longer) since ending treatment on another investigational device or drug trial(s). Other investigational procedures while participating in this trial are excluded.
Diagnostic Assessments During Screening
Participant 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 \[SGOT\]) \> 2.0 times the upper limit of normal (ULN).
Corrected QT interval (QTc) \> 500 ms, using Bazett's formula.
QTc ≥ 450 to ≤ 500 ms, using Bazett's formula, unless written permission to enroll is provided by the investigator after consultation with a pediatric cardiologist.
Participant has a clinically significant ECG abnormality during screening that, in the opinion of the investigator, could pose a risk to participant safety or interfere with the trial evaluation.
Within the 60 days prior to enrollment
• New onset or worsening of a pre-existing seizure disorder.
Other Exclusions
Participants aged 28 days to 6 months of age who were born prematurely at \< 36 weeks gestational age.
Female participant 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 trial 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 participants of childbearing potential unwilling to use 1 highly-effective or acceptable method of contraception during treatment and for an additional 3 months after the last dose of investigational product.
Participant has known sensitivity to etelcalcetide or excipients to be administered during dosing.
Participant likely to not be available to complete all protocol-required trial visits or procedures, and/or to comply with all required trial procedures (eg, to the best of the participant and investigator's knowledge).
History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety or interfere with the trial evaluation, procedures, or completion.
Participant has previously entered this trial.

Intervenciones

drug

Etelcalcetide

Etelcalcetide has been shown to be safe and efficacious in treating adult CKD patients with SHPT by simultaneously controlling iPTH, Ca, and phosphorus and has recently been approved for use in adult patients with SHPT treated with hemodialysis in both the United States and Europe

other

Standard of Care

Standard of care, which can include therapy with vitamin D sterols, Ca supplementation, and/or phosphate binders

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Etelcalcetide

Standard of Care

Ubicaciones

Fresenius Escobar

Hospital Italiano

Centro Infantil Del Rinon

Patrocinadores

Contactos

Amgen Call Center