Clinical trial NCT03633708: A Study of Etelcalcetide in Pediatric Subjects With Secondary Hyperparathyroidism and Chronic Kidney Disease on Hemodialysis
Official title: Phase 3, Randomized, Open-label, Controlled, Multiple Dose, Efficacy, Safety, Pharmacokinetic, and Pharmacodynamic Study of Etelcalcetide in Pediatric Subjects 28 Days to < 18 Years of Age With Secondary Hyperparathyroidism and Chronic Kidney Disease Receiving Maintenance Hemodialysis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Secondary Hyperparathyroidism
Chronic Kidney Disease
Keywords: sHPT
CKD
pediatric
Secondary Hyperparathyroidism
Chronic Kidney disease
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2018-08-16
Enrollment: 56
Sex: ALL
Minimum age (years): 0
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: SHPT is a common and serious co-morbidity that develops relatively early in the course of CKD, worsens with declining kidney function, and is associated with serious complications in children on dialysis. Children on dialysis experience a wide spectrum of bone abnormalities and growth retardation, in addition to increased risk for cardiovascular morbidity and mortality that manifests early in their adulthood. Traditional therapies for SHPT (eg, vitamin D sterols) are widely used in the pediatric dialysis population, and have the potential to aggravate complications of the disease by increasing serum calcium (Ca), serum phosphorus, and serum Ca times serum phosphorus product.

Etelcalcetide has been shown to be safe and efficacious in treating adult CKD patients with SHPT by simultaneously controlling intact parathyroid hormone (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. Although no previous studies have been conducted in pediatric patients with etelcalcetide (one single dose pharmacokinetic \[PK\] study is currently ongoing),Amgen anticipates minimal to moderate risk with a possibility of direct benefit to the pediatric subjects (age 28 days to 18 years) in this study. The burden of complications of SHPT in the pediatric dialysis population and the limitations of current standard therapy, underscore the need for studies of etelcalcetide in these patients to address this unmet medical need and inform the pediatric nephrology community of the potential use of etelcalcetide in children on hemodialysis with critical safety and efficacy data.

Eligibility criteria: Inclusion criteria

* Age of 28 days or older and less than 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 ≥ 400 pg/mL (42 pmol/L) during screening, on separate days and within 2 weeks of enrolment.
* Serum cCa value ≥ 9.0 mg/dL (2.25 mmol/L) for subjects ≥ 2 years of age and older and serum cCa value ≥ 9.6 mg/dL (2.4 mmol/L) for subjects 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 study.
* 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.

Exclusion Criteria Disease Related

* 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 study period.
* Anticipated or scheduled kidney transplant during the study period.
* Subject 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.
* 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 subject 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 subject 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 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 or 5 half-lives (whichever is longer) 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 \[SGOT\]) \> 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.
* Subject has a clinically significant electrocardiogram (ECG) abnormality during screening that, in the opinion of the investigator, could pose a risk to subject safety or interfere with the study evaluation.

Within the 60 days prior to enrollment

• New onset or worsening of a pre-existing seizure disorder.

Other Exclusions

* Subjects aged 28 days to 6 months of age who were born prematurely at \< 36 weeks gestational age.
* 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 contraception during treatment and for an additional 3 months after the last dose of investigational product.
* 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 (eg, 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) 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 has previously entered this study

Primary outcomes:
measure: Proportion of participants with ≥ 30% reduction from baseline in intact parathyroid hormone (iPTH) level during the efficacy assessment phase (EAP)
timeFrame: Baseline and Weeks 20-27
Secondary outcomes:
measure: Maximum serum concentration (Cmax) of etelcalcetide
timeFrame: 10-30 minutes post dose on Day 1 and 10-30 minutes post dose on Weeks 5, 9, 13, 17, and 21
measure: Minimum serum concentration (Cmin) of etelcalcetide
timeFrame: 10-30 minutes post dose on Day 1 and 10-30 minutes post dose on Weeks 5, 9, 13, 17, and 21
measure: Incidence of adverse events
timeFrame: Day 1 to 30 days after last dose of etelcalcetide (up to approximately 30 weeks)
measure: Frequency of hypocalcemia
timeFrame: Up to approximately 30 Weeks
measure: Number of participants with corrected serum calcium levels at any time during the study
timeFrame: Up to approximately 30 Weeks
measure: Number of participants with serum phosphorous levels below normal for age
timeFrame: Up to approximately 30 Weeks
measure: Number of participants with predialysis iPTH levels below normal
timeFrame: Up to approximately 30 Weeks
measure: Change from baseline in systolic blood pressure
timeFrame: Week -2, Week -1, Day1, and Weeks 4, 8, 12, 16, 20, 24, and 27
measure: Change from baseline in diastolic blood pressure
timeFrame: Week -2, Week -1, Day1, and Weeks 4, 8, 12, 16, 20, 24, and 27
measure: Change from baseline in heart rate
timeFrame: Week -2, Week -1, Day1, and Weeks 4, 8, 12, 16, 20, 24, and 27
measure: Change in Tanner Stage
timeFrame: Week -2 and Week 27
measure: Change in height
timeFrame: Day 1 and Week 27
measure: Change in weight
timeFrame: Week -2, Day 1, and Week 27
measure: Achievement of ≥ 30% reduction in iPTH from baseline on two consecutive visits
timeFrame: Up to approximately 30 Weeks
measure: Mean change from baseline in predialysis iPTH
timeFrame: Baseline and Weeks 20-27
measure: Percentage change from baseline in predialysis iPTH
timeFrame: Baseline and Weeks 20-27
measure: Percentage change from baseline in corrected total serum calcium
timeFrame: Baseline and Weeks 20-27
measure: Percentage change from baseline in corrected total serum phosphorous
timeFrame: Baseline and Weeks 20-27
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Childrens Hospital of Los Angeles
state: California
city: Aurora
country: United States
facility: Childrens Hospital Colorado
state: Colorado
city: Kansas City
country: United States
facility: Childrens Mercy Hospital
state: Missouri
city: New York
country: United States
facility: Mount Sinai Kidney Center - B1 Renal Treatment
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Oklahoma City
country: United States
facility: The Childrens Hospital at Oklahoma University Medical Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Childrens Hospital of Philadelphia
state: Pennsylvania
city: Dallas
country: United States
facility: Childrens Medical Center Dallas
state: Texas
city: Salt Lake City
country: United States
facility: Primary Childrens Hospital Outpatient Services
state: Utah
city: Cuidad Autonoma de Buenos Aires
country: Argentina
facility: Hospital Italiano
state: Buenos Aires
city: Escobar
country: Argentina
facility: Fresenius Escobar
state: Buenos Aires
city: San Miguel de Tucuman
country: Argentina
facility: Centro Infantil Del Rinon
state: Tucuman
city: New Delhi
country: India
facility: Fortis Flt Lt Rajan Dhall Hospital
state: Delhi
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
state: Delhi
city: New Delhi
country: India
facility: Sir Ganga Ram Hospital
state: Delhi
city: Bangalore
country: India
facility: Manipal Hospital
state: Karnataka
city: Belagavi
country: India
facility: KLES Dr Prabhakar Kore Hospital and Medical Research Centre
state: Karnataka
city: Kolkata
country: India
facility: NRS Medical College and Hospital
state: West Bengal
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Yangsan-si, Gyeongsangnam-do
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Kota Bharu
country: Malaysia
facility: Hospital Raja Perempuan Zainab II
state: Kelantan
city: Seremban
country: Malaysia
facility: Hospital TuanKu Jaafar
state: Negri Sembilan
city: Kuala Lumpur
country: Malaysia
facility: Hospital Wanita Dan Kanak-Kanak Kuala Lumpur
state: Wilayah Persekutuan
city: Moscow
country: Russian Federation
facility: SBHI Pediatrics city clinical hospital of Saint Vladimir
city: Saint Petersburg
country: Russian Federation
facility: SBHI Children's City Multidisciplinary Clinical Specialized Center of High Medical Technologies
city: Samara
country: Russian Federation
facility: State Budgetary Healthcare Institution Samara Regional Clinical Hospital na V D Seredavin
city: Singapore
country: Singapore
facility: National University Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi Hastanesi
city: Ankara
country: Turkey
facility: Baskent Universitesi Ankara Hastanesi
city: Ankara
country: Turkey
facility: Gazi Universitesi Saglik Arastirma ve Uygulama Merkezi Gazi Hastanesi
city: Ankara
country: Turkey
facility: Ankara Bilkent Sehir Hastanesi
city: Elazig
country: Turkey
facility: Firat Universitesi Hastanesi
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Cerrahpasa Tip Fakultesi
city: Istanbul
country: Turkey
facility: Marmara Universitesi Tip Fakultesi Hastanesi
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi Hastanesi
city: Kayseri
country: Turkey
facility: Erciyes Universitesi Tip Fakultesi Hastanesi
city: Kyiv
country: Ukraine
facility: National Childrens Specializated Hospital Okhmadit
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: