Phase III, multicenter, open-label, randomized clinical trial to evaluate efficacy of Sodium Zirconium Cyclosilicate (Lokelma) compared to standard of care to manage hyperkalemia in patients with chronic kidney disease (CKD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Instituto De Investigacion Sanitaria Fundacion Para La Investigacion Del Hospital Clinico De Valencia-INCLIVA

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

12 Dec 2022 → ongoing

Decision date (initial)

2024-09-16

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca

External identifiers

EU CT number

2024-517631-43-00

EudraCT number

2020-003229-47

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To analyze the proportion of patients achieving sK of < 5.5 mEq/L with Sodium zirconium cyclosilicate (SZC) versus discontinuation of RAASi and/or MRA in patients with hyperkalemia and non dialysis CKD.

Conditions and MedDRA coding

Hyperkalemia in patients with chronic kidney disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patients must present serum potassium levels of 5.5-6.5 mEq/L at patient selection visit (V0)
2. Patients must present serum potassium levels of 5.0-6.5 mEq/L at randomization visit (V1).
3. Provision of patient or legal representative informed consent prior to any study specific procedures
4. Individuals receiving background standard of care for HF and treated according to locally recognized guidelines. Specific treatment should include RAASi and/or MRA treatment at first consultation and at least should have been stable for ≥ 4 weeks at maximum tolerated doses
5. Patients with CKD not on dialysis (Stages 2-5: estimated glomerular filtration rate (eGFR) between 15-60 ml/min/1,73m2 or eGFR between 60-90 ml/min/ 1.73 m2 with albuminuria/creatinuria (> 30 mg/g) in the previous three months). The estimated GFR can be reported by the laboratory or calculated by the researcher with serum creatinine, age, and sex (CKD-EPI equation).
6. Over 18 years at the time of signing ICF
7. Negative pregnancy test (urine or serum) for female subjects of childbearing potential
8. Female subjects must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign ICF) and for 3 months after the last dose of SZC. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used

Exclusion criteria 17

1. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
2. Previous enrollment or randomization in the present study
3. HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease.
4. Current acute decompensated HF, hospitalization due to decompensated HF, myocardial infarction, unstable angina, stroke or transient ischemic attack within 12 weeks prior to enrollment
5. Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting or valvular repair/replacement within 12 weeks prior to enrollment or planned to undergo any of these operations after randomization).
6. Implantation of a Cardiac Resynchronization Therapy (CRT) device or Implantable Cardioverter Defibrillator (ICD) within 12 weeks prior to enrollment or intent to perform atrial fibrillation ablation or to implant a CRT or ICD device.
7. Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or transplantation or implantation expected after randomization
8. Oropharingeal dysfunction that precludes normal swallow
9. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.
10. Patients with amputated limbs or pacemaker devices will be excluded of bioimpedance analysis
11. Participation in another clinical study with an investigational product during the last 6 months
12. Patients with a known hypersensitivity to SZC or any of the excipients of the product
13. Treated with potassium binding resins such as sodium polystyrene sulfonate (SPS; e.g. Kayexalate®) or calcium polystyrene sulfonate (CPS; e.g. Resonium®) or the cation exchange polymer, patiromer sorbitex calcium (Veltassa®), within 7 days prior to the first dose of study drug
14. Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements
15. Subjects with a family history of long QT syndrome, presence of cardiac arrhythmias or conduction defects that require immediate treatment, or a QTc (corrected QT interval) of ≥ 550 msec.
16. History of QT prolongation associated with other medications that required discontinuation of that medications
17. Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of patients achieving serum potassium < 5.5mEq/L at three or all timepoints (7, 30, 60 or 90 days) after follow up (90 days) in both groups.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Instituto De Investigacion Sanitaria Fundacion Para La Investigacion Del Hospital Clinico De Valencia-INCLIVA

Sponsor organisation

Instituto De Investigacion Sanitaria Fundacion Para La Investigacion Del Hospital Clinico De Valencia-INCLIVA

Address

Avenida Menendez Y Pelayo 4

City

Valencia

Postcode

46010

Country

Spain

Scientific contact point

Organisation

Instituto De Investigacion Sanitaria Fundacion Para La Investigacion Del Hospital Clinico De Valencia-INCLIVA

Contact name

UICEC

Public contact point

Organisation

Instituto De Investigacion Sanitaria Fundacion Para La Investigacion Del Hospital Clinico De Valencia-INCLIVA

Contact name

UICEC

Locations

1 EU/EEA country · 4 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 4 files

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

Application history

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