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

Hyperphosphatemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02688764
• Other study ID #: PA-CL-PED-01
• Status: Terminated
• Phase: Phase 3
• Start date: May 26, 2016
• Est. completion date: February 21, 2019

Study information

• Verified date: August 2019
• Source: Vifor Fresenius Medical Care Renal Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 85
• Est. completion date: February 21, 2019
• Est. primary completion date: February 21, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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)

Related Conditions & MeSH terms

• Hyperphosphatemia

Intervention

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.
• 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.

Locations

Country	Name	City	State
France	Hôpital Jeanne de Flandre	Lille
France	Chu de Lyon - Hopital Femme Mere Enfant	Lyon
France	Service de Néphrologie et Endocrinologie pédiatriques	Montpellier cedex 5
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	Universitätsklinikum Gießen und Marburg GmbH	Marburg
Lithuania	Hospital Of Lithuanian University Of Health Sciences Kaunas Clinics	Kaunas
Lithuania	Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos	Vilnius
Poland	Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa w Bialymstoku	Bialystok
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Uniwersytecki Szpital Dzieciecy w Krakowie - Prokocimiu	Krakow
Poland	Instytut "Pomnik - Centrum Zdrowia Dziecka"	Warszawa
Romania	Spitalul Clinic Fundeni Bucuresti	Bucure?ti	Bucharest
Romania	Spitalul Clinic de Urgenta pentru copii "Maria Sklodowska Curie"	Bucuresti	Bucharest
Russian Federation	Children's Republican Clinical Hospital	Kazan
Russian Federation	St. Vladimir Children's City Clinical Hospital	Moscow
Russian Federation	St. Petersburg GBUZ "Children's City Hospital No. 1"	Saint Petersburg
United States	The University of New Mexico	Albuquerque	New Mexico
United States	University of Michigan Hospital	Ann Arbor	Michigan
United States	Emory-Children's Center	Atlanta	Georgia
United States	University of Alabama at Birmingham School of Medicine	Birmingham	Alabama
United States	The University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Texas Children's Hospital - Texas Children's Feigin Center	Houston	Texas
United States	The University of Texas Medical School at Houston	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Nicklaus Children's Hospital	Miami	Florida
United States	University of Miami - Miller School of Medicine	Miami	Florida
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Weill Cornell Medical College	New York	New York
United States	University of Oklahoma Medical Center	Oklahoma City	Oklahoma
United States	Nemours Children's Clinic - Orlando	Orlando	Florida
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Oregon Health and Science University, Doernbecher Children's Hospital	Portland	Oregon
United States	Washington University School of Medicine in St. Louis	Saint Louis	Missouri
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Vifor Fresenius Medical Care Renal Pharma

Countries where clinical trial is conducted

United States,  France,  Germany,  Lithuania,  Poland,  Romania,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	Serum Phosphorus Values at Each Visit		through study completion, up to 34 weeks after treatment start date
Secondary	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
Secondary	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
Secondary	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
Secondary	Serum iPTH Levels at Each Time Point and Change From Baseline		From baseline through study completion, up to 34 weeks after treatment start date
Secondary	Ferritin Values at Each Time Point and Change From Baseline		From baseline through study completion, up to 34 weeks after treatment start date
Secondary	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
Secondary	Iron Values at Each Time Point and Change From Baseline		From baseline through study completion, up to 34 weeks after treatment start date
Secondary	Transferrin Values at Each Time Point and Change From Baseline		From baseline through study completion, up to 34 weeks after treatment start date
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Osteocalcin-CL Values at Each Time Point and Change From Baseline		From baseline through study completion, up to 34 weeks after treatment start date
Secondary	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