Effect of patiromer in children under 12 years of age with high blood potassium levels

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vifor Pharma Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

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

Trial duration

14 Feb 2025 → ongoing

Decision date (initial)

2025-02-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sponsor: Vifor Pharma Inc.

External identifiers

EU CT number

2023-505252-21-00

ClinicalTrials.gov

NCT05766839

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Safety, Pharmacodynamic, Dose response

To assess change in potassium levels from baseline to Day 28 following administration of different doses of patiromer administered in children 0 to <12 years of age with hyperkalaemia

Secondary objectives 1

1. To assess the safety and tolerability of patiromer in children 0 to <12 years of age with hyperkalaemia.

Conditions and MedDRA coding

Hyperkalemia

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-001720-PIP01-14

Plan to share IPD

Yes

IPD plan description

CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at [email protected] .

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Paediatric participants (<12 years of age) with hyperkalaemia at screening.
2. Participant’s age should not reach 12 years during the 28 days of the PD/ dose-ranging period.
3. Participant is able to receive regular external feeding and medication, including via tubes, e.g., PEG or entero-gastric feeding tube.
4. At screening/baseline, the results from 2 separate and consecutive potassium assessments using the same measurement method (whole blood, plasma, or serum) need to be above the age-appropriate upper limit of normal (ULN). At least 1 sample needs to be taken at screening/baseline and 1 sample should not be older than 30 days, i.e., a historical sample. The average of the 2 potassium values needs to be above the age appropriate ULN of the measurement method plus 0.5 mEq/l (equivalent to 0.5 mmol/l). If the 2 samples are taken on the day of screening/baseline, the 2 individual potassium values must not differ from each other by more than 0.5 mEq
5. In the opinion of the Investigator, the participant is expected to require treatment for hyperkalaemia for at least 28 days upon enrolment in the study.
6. If taking any RAASi, beta blockers, fludrocortisone, or diuretic medications, must be on a stable dose for at least 14 days prior to screening.
7. Parent(s) or legally acceptable representative(s) has provided the appropriate written informed consent, in accordance with local regulations. The assent of the child should also be obtained when appropriate or if requested by the IRB/EC/IEC. The written informed consent must be provided before any study-specific procedures are performed including screening procedures.
8. Parent(s) or legally authorised representative(s) or another appropriate person delegated by the legally authorised representatives must be available to help the study-site personnel ensure follow-up; accompany the participant to the study site on each assessment day according to the Schedule of Events (Table 1, Table 2) (e.g., able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures); accurately and reliably dispense investigational product as directed.
9. Non-Norway sites: Females of child bearingchildbearing potential must be non-lactating; must have a negative pregnancy test at screening; and must have used an effective, acceptable form of contraception (e.g., abstinence) for at least 1 month prior to patiromer administration. Females of child bearing potential must agree to continue using contraception throughout the study and for 1 month after the last dose of patiromer
10. If undergoing peritoneal dialysis, participants must be on a stable treatment plan for a minimum of 4 weeks prior to screening, or at least 8 weeks prior to screening if newly initiated on peritoneal dialysis.

Exclusion criteria 20

1. Preterm birth infants with <37 weeks of gestation cannot be included in Cohort 3.
2. In the opinion of the Investigator, any medical condition, uncontrolled systemic disease, or serious intercurrent illness that would significantly decrease study compliance or jeopardise the safety of the participant or potentially affect the quality of the data such as: hyperkalaemia at screening that requires emergency intervention; cardiovascular event or intervention within 3 months prior to screening; a haemodynamically unstable arrhythmia; hospitalisation for heart failure within the past 3 months; poorly controlled blood pressure; poorly controlled diabetes mellitus or frequent need for adjustment in insulin prescription or recent hospitalisation for treatment of hyper or hypoglycaemia.
3. If the child is being breastfed: a) There is suspicion of current alcohol or substance misuse/abuse in breastfeeding mother b) The breastfeeding mother is taking potassium supplements
4. Participants who due to their general condition, e.g., anaemia or low body weight, are not suitable to have blood volume withdrawn as specified in the Schedule of Events
5. Participant with pseudo-hyperkalaemia due to haemolysis or to abnormally high numbers of platelets (above ULN), leukocytes (above ULN), or erythrocytes (above ULN) at screening based on results obtained from the local laboratory.
6. Any participant with evidence of potential potassium-related 12-lead electrocardiogram (ECG) changes (i.e., changes consistent with hyper- or hypokalaemia) at screening.
7. Any participant with serum magnesium <1.4 mg/dl (0.58 mmol/l) at screening/baseline.
8. Any of the following renal conditions: maintenance haemodialysis, renal artery stenosis, and acute kidney injury (defined by 2012 Kidney Disease Improving Global Outcomes) or a history of acute renal insufficiency in the past 3 months. Note: chronic kidney disease (CKD) is not excluded.
9. A history of or current diagnosis of a severe gastrointestinal (GI) diagnosis or surgery that could affect GI transit of the drug (delayed gastric emptying), such as a severe swallowing disorder, severe gastroesophageal reflux, uncorrected pyloric stenosis, intussusception, any other intestinal obstruction (e.g., Hirschsprung disease, chronic intestinal pseudo obstruction, clinically significant postsurgical abdominal adhesions) or any gut-shortening surgical procedure prior to screening. Pre-gastric above-mentioned pathologies may be disregarded in case of existence of a PEG or entero-gastric feeding tube, as the PEG or entero gastric feeding tube will serve for nutrition and investigational product administration
10. Liver enzymes (alanine aminotransferase or aspartate aminotransferase) more than 3 times the ULN at screening, based on the local laboratory, as well as the participant’s respective age
11. If the child is being breastfed: a) There is suspicion of current alcohol or substance misuse/abuse in breastfeeding mother b) The breastfeeding mother is taking potassium supplements
12. Scheduled for kidney transplant procedure during the first 28 days after Day 1.
13. History of sudden infant death in a sibling (only for participants <2 years of age at screening
14. Has severe hypoxaemia, respiratory acidosis, asphyxia, or hypotension 3 months before screening based on assessment of the Investigator.
15. Participant treated with sodium polystyrene sulphonate, calcium polystyrene sulphonate, or sodium zirconium cyclosilicate within the last 48 hours prior to fulfilling the baseline potassium assessments requested in Inclusion Criterion 4.
16. Use of the following medications if doses have not been stable for at least 14 days prior to screening or if doses are anticipated to change during the 4-week PD/dose-ranging period: digoxin, bronchodilators, theophylline, heparins (including low molecular heparins), tacrolimus, mycophenolate mofetil, cyclosporine, trimethoprim, or cotrimoxazole.
17. Use of any investigational product for an unapproved indication within 30 days prior to screening or within 5 half-lives, whichever is longer
18. Known hypersensitivity to patiromer or its components
19. In the opinion of the Investigator, parent(s) or legal representative(s) inability to comply with the protocol.
20. Norway sites only: Females of child-bearing potential (i.e., those who have reached menarche on or before the baseline visit).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Changes in potassium levels from baseline to Day 28.

Secondary endpoints 6

1. Changes in potassium levels from baseline to Day 3, Day 7, and Day 14 and end of the study Part 1 and during the optional safety-extension period.
2. Occurrence of TEAEs and SAEs.
3. Change in vital signs, 12-lead ECG, and clinical safety laboratory evaluations.
4. Laboratory safety endpoints of special interest including occurrence of blood potassium: − Below the LLN. − Above the ULN
5. Occurrence of blood magnesium: − <1.4 mg/dl (<0.58 mmol/l) − <1.2 mg/dl (<0.49 mmol/l) − <1.0 mg/dl (<0.41 mmol/l)
6. Occurrence of serum calcium, phosphate, fluoride, creatinine, bicarbonate, and blood urea nitrogen levels that are outside of normal range of the respective age.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vifor Pharma Inc.

Sponsor organisation

Vifor Pharma Inc.

Address

1000 1st Avenue Suite 300

City

King Of Prussia

Postcode

19406-1333

Country

United States

Scientific contact point

Organisation

Vifor Pharma Inc.

Contact name

Medical Contact Point

Public contact point

Organisation

Vifor Pharma Inc.

Contact name

Medical Contact Point

Third parties 12

Locations

11 EU/EEA countries · 16 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 70 files

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

Application history

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