A Study to Investigate the Safety and Efficacy of PA21 (Velphoro®) and Calcium Acetate (Phoslyra®) in Paediatric and Adolescent Chronic Kidney Disease (CKD) Patients With Hyperphosphataemia

Phase 3TerminatedNCT02688764

Vifor Fresenius Medical Care Renal Pharma85 enrolled

Overview

This is a Phase 3, Open-label, Randomised, Active-controlled, Parallel Group, Multicentre Study to Investigate the Safety and Efficacy of PA21 (Velphoro®) and Calcium Acetate (Phoslyra®) in Paediatric and Adolescent CKD Patients with Hyperphosphataemia. The aim of this Phase 3 clinical study is to demonstrate similar efficacy of PA21 (Velphoro) in paediatric and adolescent patients with CKD, and to provide safety and dosing information for this patient population. The Phoslyra (comparator) group provides information for a descriptive comparison of PA21 against a commonly used calcium-based phosphate binder (calcium acetate).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hyperphosphatemia

Interventions

During Stage 1 (Open-Label Dose Titration; up to 10 weeks), PA21 subjects will receive PA21 at a starting dose based on their age. Dose of PA21 will be increased or decreased as required for efficacy (to achieve age specific target serum phosphorus level), provided a subject has been receiving that dose for a minimum of 2 weeks, and for safety or tolerability reasons at any time. During Stage 2 (Open-Label Safety Extension, 24 week safety extension),subjects will continue on the dose received at the end of Stage 1, unless a dose change is required. Doses may be titrated for efficacy (to achieve age specific target Serum phosphorus levels), provided a subject has been receiving that dose for a minimum of 2 weeks, and for safety or tolerability reasons at any time during Stage 2.

Calcium Acetate (Phoslyra®)DRUG

During Stage 1 (Open-Label Dose Titration; up to 10 weeks), Phoslyra subjects will receive Phoslyra either at a starting dose based on their weight or, if considered more appropriate by the Investigator, at an equivalent dose of their previous phosphate binder (PB), calcium-based or sevelamer. Dose of Phoslyra will be increased or decreased as required for efficacy (to achieve age specific target serum phosphorus level), provided a subject has been receiving that dose for a minimum of 2 weeks, and for safety or tolerability reasons at any time. During Stage 2 (Open-Label Safety Extension, 24 week safety extension),subjects will continue on the dose received at the end of Stage 1, unless a dose change is required. Doses may be titrated for efficacy (to achieve age specific target Serum phosphorus levels), provided a subject has been receiving that dose for a minimum of 2 weeks, and for safety or tolerability reasons at any time during Stage 2.

Eligibility

Sex: ALLMax age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Subjects 0 to \<18 years at time of consent. 2. Subjects with hyperphosphataemia 3. Subjects ≥1 year with CKD Stages 4-5 defined by a glomerular filtration rate \<30 mL/min/1.73 m2 or with CKD Stage 5D receiving adequate maintenance haemodialysis (HD) or peritoneal dialysis (PD) for at least 2 months prior to screening. 4. Subjects \<1 year must have CKD. 5. Appropriate written informed consent and, where appropriate/required assent, have been provided. Exclusion Criteria: 1. Subjects with hypercalcaemia at screening 2. Subjects with intact parathyroid hormone (iPTH) levels \>700 pg/mL at screening. 3. Subjects who are PB naïve who weigh \<5 kg at screening. Subjects receiving stable doses of PBs who weigh \<6 kg at screening 4. Subjects requiring feeding tube sizes ≤6 FR (French catheter scale). 5. Subjects with history of major gastrointestinal surgery or significant gastrointestinal disorders. 6. Subjects with hypocalcaemia (serum total corrected calcium \<1.9 mmol/L; \<7.6 mg/dL) at screening. 7. Subject is pregnant (e.g., positive human chorionic gonadotropin test) or breast feeding. 8. Subject has a significant medical condition(s)

Locations (38)

University of Alabama at Birmingham School of Medicine

Birmingham, Alabama, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

University of Miami - Miller School of Medicine

Miami, Florida, United States

Nicklaus Children's Hospital

Miami, Florida, United States

Nemours Children's Clinic - Orlando

Orlando, Florida, United States

Outcomes

Primary Outcomes

Change in Serum Phosphorus Level From Baseline to the End of Stage 1 in the PA21 Group

Time frame: From Baseline to the End of Stage 1 (up to 10 weeks after treatment start date)

Number and Percentage of Participants Who Withdrew Due to Treatment Emergent Adverse Events

Any adverse event Leading to Study Drug Withdrawal is considered.

Time frame: through study completion, up to 34 weeks after treatment start date

Number and Percentage of Participants With Any Treatment Emergent Adverse Event

Please note that in this section we are presenting just the overview of the adverse events experienced by the trial participants, in particular, the number of participants with at least one TEAEs until end of stage 2. Please refer to the detailed tables included on the Adverse Event Module for specifics.

Time frame: through study completion, up to 34 weeks after treatment start date

Secondary Outcomes

Change in Serum Phosphorus Level From Baseline to the End of Stage 1 in the Phoslyra Group

Time frame: From Baseline to the End of Stage 1 (up to 10 weeks after treatment start date)

Change in Serum Phosphorus Level From Baseline to the End of Stage 2 in Both Groups

Time frame: From baseline to study completion, up to 34 weeks after treatment start date

Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage

Number and percentages of participants with serum phosphorus levels below, within and above age-dependent target ranges at baseline, at the end of Stage 1 and at the end of Stage 2. The age target ranges for serum phosphorus levels are: * 0 to \<1 year 1.62-2.52 mmol/L * 1 year to \<6 years 1.45-2.10 mmol/L * 6 years to \<13 years 1.16-1.87 mmol/L * 13 years to ≤18 years 0.74-1.45 mmol/L

Time frame: through study completion, up to 34 weeks after treatment start date

Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage

Number and percentages of participants with serum phosphorus levels below, within and above age-dependent normal ranges at baseline, at the end of Stage 1 and at the end of Stage 2. The age related normal ranges for serum phosphorus levels are: * 0 to \<1year 1.36 - 2.62 mmol/L * 1 year to \<6 years 1.03 - 1.97 mmol/L * 6 years to \<9 years 1.03 - 1.97 mmol/L * 9 years to \<10 years 1.03 - 1.97 mmol/L * 10 years to \<15 years 1.00 - 1.94 mmol/L * 15 years to ≤18 years 0.71 - 1.65 mmol/L

Time frame: through study completion, up to 34 weeks after treatment start date

Serum Phosphorus Values at Each Visit

Time frame: through study completion, up to 34 weeks after treatment start date

Serum Total Corrected Calcium at Each Time Point and Change From Baseline