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

Study Overview
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Brief Summary
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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).

Official Title
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An Open-label, Randomised, Active-controlled, Parallel Group, Multicentre, Phase 3 Study to Investigate the Safety and Efficacy of PA21 (Velphoro®) and Calcium Acetate (Phoslyra®) in Paediatric and Adolescent CKD Patients With Hyperphosphataemia

Conditions
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Hyperphosphatemia

Intervention / Treatment
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* Drug: PA21 (Velphoro®)
* Drug: Calcium Acetate (Phoslyra®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects 0 to <18 years at time of consent. Subjects with hyperphosphataemia 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. Subjects <1 year must have CKD. Appropriate written informed consent and, where appropriate/required assent, have been provided. Exclusion Criteria: Subjects with hypercalcaemia at screening Subjects with intact parathyroid hormone (iPTH) levels >700 pg/mL at screening. Subjects who are PB naïve who weigh <5 kg at screening. Subjects receiving stable doses of PBs who weigh <6 kg at screening Subjects requiring feeding tube sizes ≤6 FR (French catheter scale). Subjects with history of major gastrointestinal surgery or significant gastrointestinal disorders. Subjects with hypocalcaemia (serum total corrected calcium <1.9 mmol/L; <7.6 mg/dL) at screening. Subject is pregnant (e.g., positive human chorionic gonadotropin test) or breast feeding. Subject has a significant medical condition(s)

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PA21 (Velphoro®)<br>PA21 (Velphoro®), chewable tablets 500 mg iron PA21 (Velphoro®), chewable tablets 250 mg iron PA21 (Velphoro®), powder for oral suspension 500 mg iron PA21 (Velphoro®), powder for oral suspension 250 mg iron PA21 (Velphoro®), powder for oral suspension 125 mg iron | Drug: PA21 (Velphoro®)<br>* 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.<br>* Other names: sucroferric oxyhydroxide;|
| Active Comparator: Calcium Acetate (Phoslyra®)<br>Calcium Acetate (Phoslyra®) - Oral Solution: 667 mg calcium acetate per 5 mL. | Drug: Calcium Acetate (Phoslyra®)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum Phosphorus Level From Baseline to the End of Stage 1 in the PA21 Group |  | 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. | 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. | through study completion, up to 34 weeks after treatment start date | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum Phosphorus Level From Baseline to the End of Stage 1 in the Phoslyra Group |  | 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 |  | 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 | 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 | through study completion, up to 34 weeks after treatment start date | 
| Serum Phosphorus Values at Each Visit |  | through study completion, up to 34 weeks after treatment start date | 
| Serum Total Corrected Calcium at Each Time Point and Change From Baseline |  | From baseline through study completion, up to 34 weeks after treatment start date | 
| Participants With Sustained Hypercalcaemia | Number and percentages of participants with at least 1 episode of sustained hypercalcaemia (defined as total calcium value above the upper safety limit confirmed by repeat sample 1 week later) during the study | through study completion, up to 34 weeks after treatment start date | 
| Serum Total Corrected Calcium-Phosphorus Product at Each Time Point and Change From Baseline | Summary statistics of Serum total corrected calcium-phosphorus product at each time point and change from baseline, where serum total corrected calcium-phosphorus product correspond to the product of serum total calcium and Phosphorus, expressed in mmol^2/L^2 | From baseline through study completion, up to 34 weeks after treatment start date | 
| Serum iPTH Levels at Each Time Point and Change From Baseline |  | From baseline through study completion, up to 34 weeks after treatment start date | 
| Ferritin Values at Each Time Point and Change From Baseline |  | From baseline through study completion, up to 34 weeks after treatment start date | 
| Unsaturated Iron Binding Capacity Values at Each Time Point and Change From Baseline |  | From baseline through study completion, up to 34 weeks after treatment start date | 
| Iron Values at Each Time Point and Change From Baseline |  | From baseline through study completion, up to 34 weeks after treatment start date | 
| Transferrin Values at Each Time Point and Change From Baseline |  | From baseline through study completion, up to 34 weeks after treatment start date | 
| 25-Hydroxy Vitamin D Values at Each Time Point and Change From Baseline |  | From baseline through study completion, up to 34 weeks after treatment start date | 
| Bone Specific Alkaline Phosphatase Values at Each Time Point and Change From Baseline |  | From baseline through study completion, up to 34 weeks after treatment start date | 
| Type I Collagen C-Telopeptides Values at Each Time Point and Change From Baseline |  | From baseline through study completion, up to 34 weeks after treatment start date | 
| Fibroblast Growth Factor 23 Values at Each Time Point and Change From Baseline |  | From baseline through study completion, up to 34 weeks after treatment start date | 
| Osteocalcin-CL Values at Each Time Point and Change From Baseline |  | From baseline through study completion, up to 34 weeks after treatment start date | 
| Tartrate-resistant Acid Phosphatase 5b Values at Each Time Point and Change From Baseline |  | From baseline through study completion, up to 34 weeks after treatment start date | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PA21, phosphate binder