An Open-label Study to Assess Safety and Efficacy of SZC in Paediatric Patients With Hyperkalaemia
brief summary
Sodium zirconium cyclosilicate has been shown to be effective and safe in adults for the treatment of hyperkalaemia, and therefore it is expected to be beneficial in children. This study will evaluate the efficacy, safety and tolerability of sodium zirconium cyclosilicate for the treatment of hyperkalaemia in children \<18 years of age. Approximately 140 participants will enter CP at approximately 46 sites in locations including but not limited to Europe and North America for this study. Treatment will include 3 phases: the CP, MP, and LTMP. Enrolment will start in 2 cohorts, ages 6 to \< 12 years and 12 to \< 18 years. After review of accumulated data, the independent Data Monitoring Committee (iDMC) will recommend whether to open enrolment in the ages 2 to \< 6 years cohort and later in the ages 0 to \< 2 years cohort. All eligible participants with hyperkalaemia will enter an open-label Correction Phase (CP) receiving a fixed dose of SZC three times daily (TID) for up to 3 days until normokalaemia is achieved. Within each age cohorts 2 to \< 18 years, initial participants will be allocated to the dose level (DL) based on body weight equivalent to an adult 5 g TID. After recommendation of higher DLs by the iDMC, subsequent participants may be allocated in the CP to on body weight equivalent to an adult 10 g TID and then potentially on body weight equivalent to an adult 15 g TID. All participants in the ages 0 to \< 2 years cohort will be assigned to the same DL which will be decided based on data from older age cohorts. Participants who successfully achieve normokalaemia in the CP will enter a 28-day open-label Maintenance Phase (MP), which will be initiated with once daily administration of the dose received TID in the CP. During MP, the Investigator is able to titrate the dose up or down in the range 2.5 g to 15 g body weight equivalent to maintain normokalaemia. For participants who, at the end of MP, are normokalaemic or hyperkalaemic without being on maximum dose, the MP is followed by the option to continue the study in a long term maintenance phase (LTMP) where the same titration regimen is used as in MP
detailed description
Protocol title: An open-label study to assess safety and efficacy of SZC in paediatric patients with hyperkalaemia
Rationale: Sodium zirconium cyclosilicate has been shown to be effective and safe in adults for the treatment of hyperkalaemia, and therefore it is expected to be beneficial in children. This study will evaluate the efficacy, safety and tolerability of sodium zirconium cyclosilicate for the treatment of hyperkalaemia in children \<18 years of age
Primary Objective: Correction phase (CP) primary objective:
1. To evaluate the ability to achieve normokalaemia during the CP when initiating treatment with SZC of different dose levels (DLs) in children with hyperkalaemia 28-day Maintenance Phase (MP) primary objective: 2. To evaluate the ability to maintain normokalaemia during the MP when continuing SZC treatment in children achieving normokalaemia
Secondary Objectives: All phases secondary objective: 3. To evaluate the change in S-K+ in children treated with SZC
MP secondary objectives: 4. To evaluate change in serum aldosterone levels in children treated with SZC during the MP 5. To evaluate change in serum electrolytes (including bicarbonate), spot urinary pH and urinary electrolytes levels in children treated with SZC during the MP
Long-term MP (LTMP) secondary objectives: 6. To evaluate the ability of maintaining normokalaemia in children treated with SZC during the LTMP
Safety Objective: 7. To evaluate the safety and tolerability of SZC in the 3 phases (CP, MP, and LTMP)
Tertiary/Exploratory: 8. To evaluate the acceptability and palatability of SZC through the study
Overall design: This is a Phase 3, international, multi-centre, open-label study assessing different doses of SZC. The population to be studied is hyperkalaemic children \< 18 years. Dosing will mirror the regimen approved for adults using body weight equivalent doses. Enrolment will start in 2 cohorts, ages 6 to \< 12 years and 12 to \< 18 years. After review of accumulated data, the independent Data Monitoring Committee (iDMC) will recommend whether to open enrolment in the ages 2 to \< 6 years cohort and later in the ages 0 to \< 2 years cohort.
The study will be conducted in approximately 11 countries and 46 sites. All eligible participants with hyperkalaemia will enter an open-label Correction Phase (CP) receiving a fixed dose of SZC three times daily (TID) for up to 3 days until normokalaemia is achieved. Within each age cohorts 2 to \< 18 years, initial participants will be allocated to the dose level (DL) based on body weight equivalent to an adult 5 g TID. After recommendation of higher DLs by the iDMC, subsequent participants may be allocated in the CP to on body weight equivalent to an adult 10 g TID and then potentially on body weight equivalent to an adult 15 g TID. All participants in the ages 0 to \< 2 years cohort will be assigned to the same DL which will be decided based on data from older age cohorts.