An Open-label Study to Assess Safety and Efficacy of SZC in Paediatric Patients With Hyperkalaemia
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 140
- 试验地点
- 72
- 主要终点
- Correction phase (CP) primary objective: To evaluate the ability to achieve normokalaemia during the CP when initiating treatment with SZC of different dose levels in children with hyperkalaemia
研究概览
简要总结
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
详细描述
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:
- 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:
- 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
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
All phases in the study are open-label
入排标准
- 年龄范围
- 0 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of written informed consent of the participant or legal representative, and informed assent from the participant (as appropriate)
- •Female or male from birth to < 18 years of age (for the study duration).
- •Participants (including those receiving a stable peritoneal dialysis regimen for a minimum of 2 months) requiring long-term treatment of hyperkalaemia (chronic hyperkalaemia) in the age cohort ≥ 2 years, and participants requiring either short- or long-term treatment for hyperkalaemia (acute and chronic hyperkalaemia) in the age cohort < 2 years.
- •Participants must meet the following criteria for hyperkalaemia: Please refer to the Table 6 in the protocol.
- •Using digital ECG, QT interval corrected by Bazett's method (QTcB) must meet the age-appropriate parameters at Screening: a. For participants aged 0 to ≤ 3 days after birth: < 450 ms b. For participants aged >3 days to < 12 years: < 440 ms c. For participants aged ≥ 12 to < 18 years: < 450 ms (male), < 460 ms (female) All QTcB values outside the reference values specified in the protocol should be manually re-measured and re-calculated, and if there is a difference in measurement between the automatic and manual ECG, the manual measurement should always be considered correct.
- •Ability to have repeated blood draws or effective venous catheterisation.
- •Females of childbearing potential (defined as a female with potential of becoming pregnant who has experienced her menarche) must have a negative pregnancy test within one day prior to the first dose of SZC on CP Study Day 1 and sexually active females of childbearing potential must be using 2 forms of medically acceptable contraception with at least one being a barrier method
- •Optional open-label, LTMP only:
- •Provision of written informed consent of the participant or legal representative, and informed assent from the participant (as appropriate) to take part in the LTMP.
- •Participants who are normokalaemic at the end of MP or hyperkalaemic and not on maximum dose.
- •Participants who would benefit from long-term treatment for their hyperkalaemia, as judged by the Investigator.
排除标准
- •Neonates with a gestational age < 37 weeks at birth or a birth weight < 2500 g.
- •Term and preterm neonates with suspected conditions predisposing them to intestinal ischaemia (eg, perinatal hypoxia or sepsis).
- •Participants with pseudohyperkalaemia caused by excessive fist clenching to enable venepuncture, by haemolysed blood specimens, or by severe leukocytosis or thrombocytosis.
- •Participants with hyperkalaemia due to soft-tissue damage from crush injury or burns.
- •Participants with hyperkalaemia due to a secondary cause, such as dehydration, excessive use of K+ supplements, or drug use (eg, beta-adrenergic antagonists) and that would be more appropriately treated with other interventions (eg, fluid resuscitation, dose adjustments of medications).
- •6. Participants with transient iatrogenic hyperkalaemia (eg, due to treatment with tacrolimus).
- •7. Participants treated with lactulose, rifaximin (XIFAXAN™), or other nonabsorbed antibiotics for hyperammonaemia within the last 7 days.
- •8. Participants treated with CPS, sodium polystyrene sulfonate (eg, KAYEXALATE™), or patiromer within the last 4 days prior to first dose of study treatment.
- •9. Participants with a life expectancy of less than 3 months.
- •Participants who are known to have tested Human Immunodeficiency Virus (HIV) positive.
- •11. Presence of any condition which, in the opinion of the Investigator, places the participant at undue risk or potentially jeopardises the quality of the data to be generated.
- •Known hypersensitivity or previous anaphylaxis to SZC or to components thereof.
- •13. Participants with cardiac arrhythmias that require immediate treatment.
- •Participants with a family history of long QT syndrome.
- •Participants on haemodialysis.
- •Participants with a history of bowel obstruction.
- •Participants with severe gastrointestinal disorder or major gastrointestinal surgery (eg, large bowel resection).
- •18. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- •19. Previous treatment with SZC.
- •Treatment with a drug or device within the last 30 days prior to first dose of study treatment that has not received regulatory approval at the time of study entry.
- •21. Previous enrolment in the present study.
- •Females who are pregnant, breastfeeding, or planning to become pregnant.
- •Judgement by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
- •If the participant has evidence of Coronavirus disease 2019 (COVID-19) within 2 weeks prior to enrolment (a positive COVID-19 test or suspicion of COVID-19 infection) the participant cannot be enrolled in the study.
研究组 & 干预措施
Active Arm ( Sodium Zirconium Cyclosilicate SZC)
Dosage formulation: 5 g sachets 2.5 g sachets 0.25 g sprinkle capsules 0.125 g sprinkle capsules (can be manufactured to support participants <2 years of age) Route of administration: Oral Dosing instructions: SZC is provided as a powder. At the time of dosing SZC is mixed with a quantity of water or sprinkled onto semi-solid food (eg, milk, baby food, yogurt, or ice cream) within an hour of drug administration. Packaging and labelling: Study treatment will be provided in sachets packed in cartons or sprinkle capsules in high density polyethylene bottles, as appropriate for the dose. Each carton of sachets, individual sachets, and bottle of capsules will be labelled in accordance with Good Manufacturing Practice Annex 13 and per country regulatory requirement. Participant-specific dosing cards (diary) will be provided.
干预措施: Sodium Zirconium Cyclosilicate (SZC) Reduced Dose Level (Drug)
Active Arm ( Sodium Zirconium Cyclosilicate SZC)
Dosage formulation: 5 g sachets 2.5 g sachets 0.25 g sprinkle capsules 0.125 g sprinkle capsules (can be manufactured to support participants <2 years of age) Route of administration: Oral Dosing instructions: SZC is provided as a powder. At the time of dosing SZC is mixed with a quantity of water or sprinkled onto semi-solid food (eg, milk, baby food, yogurt, or ice cream) within an hour of drug administration. Packaging and labelling: Study treatment will be provided in sachets packed in cartons or sprinkle capsules in high density polyethylene bottles, as appropriate for the dose. Each carton of sachets, individual sachets, and bottle of capsules will be labelled in accordance with Good Manufacturing Practice Annex 13 and per country regulatory requirement. Participant-specific dosing cards (diary) will be provided.
干预措施: Sodium Zirconium Cyclosilicate (SZC) Dose Level 1 (DL1) (Drug)
Active Arm ( Sodium Zirconium Cyclosilicate SZC)
Dosage formulation: 5 g sachets 2.5 g sachets 0.25 g sprinkle capsules 0.125 g sprinkle capsules (can be manufactured to support participants <2 years of age) Route of administration: Oral Dosing instructions: SZC is provided as a powder. At the time of dosing SZC is mixed with a quantity of water or sprinkled onto semi-solid food (eg, milk, baby food, yogurt, or ice cream) within an hour of drug administration. Packaging and labelling: Study treatment will be provided in sachets packed in cartons or sprinkle capsules in high density polyethylene bottles, as appropriate for the dose. Each carton of sachets, individual sachets, and bottle of capsules will be labelled in accordance with Good Manufacturing Practice Annex 13 and per country regulatory requirement. Participant-specific dosing cards (diary) will be provided.
干预措施: Sodium Zirconium Cyclosilicate (SZC) Dose Level 2 (DL2) (Drug)
Active Arm ( Sodium Zirconium Cyclosilicate SZC)
Dosage formulation: 5 g sachets 2.5 g sachets 0.25 g sprinkle capsules 0.125 g sprinkle capsules (can be manufactured to support participants <2 years of age) Route of administration: Oral Dosing instructions: SZC is provided as a powder. At the time of dosing SZC is mixed with a quantity of water or sprinkled onto semi-solid food (eg, milk, baby food, yogurt, or ice cream) within an hour of drug administration. Packaging and labelling: Study treatment will be provided in sachets packed in cartons or sprinkle capsules in high density polyethylene bottles, as appropriate for the dose. Each carton of sachets, individual sachets, and bottle of capsules will be labelled in accordance with Good Manufacturing Practice Annex 13 and per country regulatory requirement. Participant-specific dosing cards (diary) will be provided.
干预措施: Sodium Zirconium Cyclosilicate (SZC) Dose Level 3 (DL3) (Drug)
Active Arm ( Sodium Zirconium Cyclosilicate SZC)
Dosage formulation: 5 g sachets 2.5 g sachets 0.25 g sprinkle capsules 0.125 g sprinkle capsules (can be manufactured to support participants <2 years of age) Route of administration: Oral Dosing instructions: SZC is provided as a powder. At the time of dosing SZC is mixed with a quantity of water or sprinkled onto semi-solid food (eg, milk, baby food, yogurt, or ice cream) within an hour of drug administration. Packaging and labelling: Study treatment will be provided in sachets packed in cartons or sprinkle capsules in high density polyethylene bottles, as appropriate for the dose. Each carton of sachets, individual sachets, and bottle of capsules will be labelled in accordance with Good Manufacturing Practice Annex 13 and per country regulatory requirement. Participant-specific dosing cards (diary) will be provided.
干预措施: Sodium Zirconium Cyclosilicate (SZC) Dose During 28 Day Maintenance Phase (Drug)
结局指标
主要结局
Correction phase (CP) primary objective: To evaluate the ability to achieve normokalaemia during the CP when initiating treatment with SZC of different dose levels in children with hyperkalaemia
时间窗: 3 days
Normokalaemia achieved in the CP within 3 days (yes/no)
28-day Maintenance Phase (MP) primary objective: To evaluate the ability to maintain normokalaemia during the MP when continuing SZC treatment in children achieving normokalaemia
时间窗: last two scheduled visits in the MP
28-day MP primary endpoint: Serum potassium (S-K+) value within normokalaemia range (yes/no) at each of the last two scheduled visits in the MP
次要结局
- Long-term MP (LTMP) secondary objectives: To evaluate the ability of maintaining normokalaemia in children treated with SZC during the LTMP(at each scheduled visit)
- MP secondary objectives: To evaluate change in serum aldosterone levels in children treated with SZC during the MP(from baseline to Week 3 of the MP)
- All phases secondary objective: To evaluate the change in S-K+ in children treated with SZC(at each scheduled visit)
- MP Secondary objective: To evaluate change in serum electrolytes (including bicarbonate), spot urinary pH and urinary electrolytes levels in children treated with SZC during the MP(from baseline to week 3 of the MP)