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

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

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 Overview

• Status: Terminated
• Conditions: Hyperphosphatemia
• Intervention / Treatment: Drug: PA21 (Velphoro®); Drug: Calcium Acetate (Phoslyra®)

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Lille, France
    • Hôpital Jeanne de Flandre
  • Lyon, France
    • CHU de Lyon - Hopital Femme Mere Enfant
  • Montpellier cedex 5, France, 34295
    • Service de Néphrologie et Endocrinologie pédiatriques
• Germany
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen
  • Marburg, Germany, 35043
    • Universitätsklinikum Gießen und Marburg GmbH
• Lithuania
  • Kaunas, Lithuania, LT-50009
    • Hospital of Lithuanian University of Health Sciences Kaunas Clinics
  • Vilnius, Lithuania, 8406
    • Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos
• Poland
  • Białystok, Poland, 15-274
    • Uniwersytecki Dziecięcy Szpital Kliniczny im. L. Zamenhofa w Białymstoku
  • Gdansk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne
  • Krakow, Poland, 30-663
    • Uniwersytecki Szpital Dzieciecy w Krakowie - Prokocimiu
  • Warszawa, Poland
    • Instytut "Pomnik - Centrum Zdrowia Dziecka"
• Romania
  • Bucharest
    • Bucureşti, Bucharest, Romania, 077120
      • Spitalul Clinic de Urgenta pentru Copii "Maria Sklodowska Curie"
    • București, Bucharest, Romania, 22322
      • Spitalul Clinic Fundeni Bucureşti
• Russian Federation
  • Kazan, Russian Federation
    • Children's Republican Clinical Hospital
  • Moscow, Russian Federation
    • St. Vladimir Children's City Clinical Hospital
  • Saint Petersburg, Russian Federation
    • St. Petersburg GBUZ "Children's City Hospital No. 1"
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham School of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
    • Miami, Florida, United States, 33136
      • University of Miami - Miller School of Medicine
    • Orlando, Florida, United States, 32827
      • Nemours Children's Clinic - Orlando
  • Georgia
    • Atlanta, Georgia, United States, 30322-1014
      • Emory-Children's Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine in St. Louis
  • New Jersey
    • Hackensack, New Jersey, United States, 07601-1914
      • Hackensack University Medical Center
    • Livingston, New Jersey, United States, 07039-5672
      • Saint Barnabas Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-0001
      • The University of New Mexico
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University, Doernbecher Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
  • Texas
    • Dallas, Texas, United States, 75390
      • The University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • The University of Texas Medical School at Houston
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital - Texas Children's Feigin Center
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PA21 (Velphoro®); 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®); 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.; Other Names: sucroferric oxyhydroxide
Active Comparator: Calcium Acetate (Phoslyra®); Calcium Acetate (Phoslyra®) - Oral Solution: 667 mg calcium acetate per 5 mL.	Drug: Calcium Acetate (Phoslyra®); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vifor Fresenius Medical Care Renal Pharma
• Investigators: Principal Investigator: Larry A Greenbaum, MD; PhD, Children's Healthcare of Atlanta at Egleston

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2016
• Primary Completion (Actual): February 21, 2019
• Study Completion (Actual): February 21, 2019

Study Registration Dates

• First Submitted: February 17, 2016
• First Submitted That Met QC Criteria: February 22, 2016
• First Posted (Estimate): February 23, 2016

Study Record Updates

• Last Update Posted (Actual): September 10, 2019
• Last Update Submitted That Met QC Criteria: August 28, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: PA21; phosphate binder
• Additional Relevant MeSH Terms: Metabolic Diseases; Phosphorus Metabolism Disorders; Hyperphosphatemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Chelating Agents; Sequestering Agents; Calcium; Calcium acetate
• Other Study ID Numbers: PA-CL-PED-01