An open-label study to assess safety and efficacy of SZC in paediatric patients with hyperkalaemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

12 Sep 2019 → ongoing

Decision date (initial)

2024-04-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB, Sweden

External identifiers

EU CT number

2023-508455-38-00

EudraCT number

2018-001331-48

ClinicalTrials.gov

NCT03813407

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Efficacy, Safety

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 3

1. All phases secondary objective: To evaluate the change in S-K+ in children treated with SZC
2. MP secondary objectives: To evaluate change in serum aldosterone levels in children treated with SZC during the MP To evaluate change in serum electrolytes (including bicarbonate), spot urinary pH and urinary electrolytes levels in children treated with SZC during the MP
3. Long-term MP (LTMP) secondary objectives: To evaluate the ability of maintaining normokalaemia in children treated with SZC during the LTMP

Conditions and MedDRA coding

Hyperkalaemia

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001539-PIP01-13

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Provision of written informed consent of the participant or legal representative, and informed assent from the participant (as appropriate)
2. Female or male from birth to <18 years of age (for the study duration)
3. 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.
4. Participants must meet the following criteria for hyperkalaemia: Please refer to the Table 6 in the protocol.
5. 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.
6. Ability to have repeated blood draws or effective venous catheterisation.
7. 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.
8. Optional, LTMP only: a. 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. b. Participants who are normokalaemic at the end of MP or hyperkalaemic and not on maximum dose. c. Participants who would benefit from long-term treatment for their hyperkalaemia, as judged by the Investigator.

Exclusion criteria 24

1. Neonates with a gestational age <37 weeks at birth or a birth weight <2500 g.
2. Term and preterm neonates with suspected conditions predisposing them to intestinal ischaemia (eg, perinatal hypoxia or sepsis).
3. Participants with pseudohyperkalaemia caused by excessive fist clenching to enable venepuncture, by haemolysed blood specimens, or by severe leukocytosis or thrombocytosis.
4. Participants with hyperkalaemia due to soft-tissue damage from crush injury or burns.
5. Participants with hyperkalaemia due to a secondary cause, such as dehydration, excessive use of K+ supplements, or drug use (eg, betaadrenergic 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.
10. 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.
12. Known hypersensitivity or previous anaphylaxis to SZC or to components thereof.
13. Participants with cardiac arrhythmias that require immediate treatment.
14. Participants with a family history of long QT syndrome.
15. Participants on haemodialysis.
16. Participants with a history of bowel obstruction.
17. 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.
20. 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.
22. Females who are pregnant, breastfeeding, or planning to become pregnant.
23. 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.
24. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. CP primary endpoint: Normokalaemia achieved in the CP within 3 days (yes/no)
2. 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

Secondary endpoints 3

1. All phases secondary endpoint: S-K+ level at each scheduled visit
2. MP secondary endpoints: Change in serum aldosterone levels from baseline to Week 3 of the MP Change in serum electrolytes (including bicarbonate), and spot urinary pH and urinary electrolytes from baseline to week 3 of the MP
3. LTMP secondary endpoints: S-K+ value within normokalaemia range (yes/no) at each scheduled visit in the LTMP

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca AB, Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca AB, Information Center

Third parties 8

Locations

4 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 45 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications