A trial to learn how well baxdrostat with dapagliflozin works compared to dapagliflozin alone and how safe it is in adults with chronic kidney disease (CKD) and high blood pressure

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astrazeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

5 Jun 2024 → ongoing

Decision date (initial)

2024-05-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response, Efficacy

To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin to slow CKD progression, assessed as the effect on change in eGFR (eGFR estimated glomerular filtration rate) over time.

Secondary objectives 5

1. 1.To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin at reducing UACR (urine albumin-creatinine ratio).
2. 2.To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin at reducing SBP (Systolic blood pressure).
3. 3.To determine whether baxdrostat/dapagliflozin compared with placebo/dapagliflozin slows CKD progression and reduces the risk of ESKD (End-stage kidney disease).
4. 4.To determine whether baxdrostat/dapagliflozin compared with placebo/dapagliflozin slows the rate of kidney function decline after the hemodynamically-mediated acute effect on GFR (Glomerular Filtration Rate).
5. To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of MACE (composite of CV death, HF with or without hospitalizuation, MI, stroke)

Conditions and MedDRA coding

Chronic kidney disease (CKD) and hypertension.

Regulatory references

Scientific advice from competent authorities

Pharmaceuticals And Medical Devices Agency, Food And Drug Administration, European Medicines Agency

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 Vivli.org. All requests 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 6

1. Participants of any sex and gender must be ≥ 18 years old, or older, at the time of signing the informed consent.
2. Participants with CKD and eGFR ≥ 30 and < 90 mL/min/1.73 m2 at screening
3. Urine albumin creatinine ratio > 200 mg/g (22.6 mg/mmol) and < 5000 mg/g (565 mg/mmol) at screening
4. Participants with history of HTN and a SBP ≥ 130 mmHg at screening and ≥ 120 mmHg at the randomisation visit
5. Stable and maximum tolerated dose of an ACE inhibitor or an ARB (not both) for at least 4 weeks prior to Screening Visit
6. 6. Central laboratory serum potassium must meet the following criteria at the Screening Visit, based on screening eGFR: o for participants with screening eGFR ≥ 45 mL/min/1.73 m2, potassium must be ≥ 3.0 and ≤ 4.8 mmol/L at the Screening Visit o for participants with screening eGFR < 45 mL/min/1.73 m2, potassium must be ≥ 3.0 and ≤ 4.5 mmol/L at the Screening Visit

Exclusion criteria 12

1. Medical Conditions 1. Systolic blood pressure > 180 mmHg, or DBP > 110 mmHg at screening.
2. Known hyperkalaemia, defined as potassium of ≥ 5.5 mmol/L within 3 months at screening.
3. Serum sodium < 135 mmol/L at the Screening Visit, determined as per central laboratory.
4. Type 1 diabetes mellitus or uncontrolled Type 2 diabetes mellitus with HbA1c > 10.5% (> 91 mmol/mol) at Screening.
5. New York Heart Association functional HF class IV at screening.
6. Stroke, transient ischaemic cerebral attack, valve implantation or valve replacement, carotid surgery, or carotid angioplasty, acute coronary syndrome, or hospitalisation for worsening heart failure within previous 3 months prior to randomisation.
7. Any dialysis (including for acute kidney injury) within 3 months prior to Screening Visit.
8. Any acute kidney injury within 3 months prior to the Screening Visit
9. History of organ transplant or bone marrow transplant, or planned organ transplant within 6 months following randomisation (including kidney transplant).
10. History or ongoing allergy/hypersensitivity, as judged by the investigator, to SGLT2 inhibitor (eg, empagliflozin) or ASI.
11. Any clinical condition requiring systemic immunosuppression therapy other than stable maintenance therapy for at least 3 months prior to Visit 1.
12. Any use of mineralocorticoid receptor antagonists (such as spironolactone, eplerenone, or finerenone), potassium-sparing diuretics (such as triamterene or amiloride), or potassium binders (such as sodium zirconium cyclosilicate, patiromer, or sodium polystyrene sulfonate) within 4 weeks prior to screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in eGFR to post treatment.

Secondary endpoints 5

1. 1. Change from baseline in UACR.
2. 2. Change from baseline in systolic BP (blood pressure).
3. 3. Kidney hierarchical composite endpoint.* *Defined as the most severe outcome of the following: 1. Death; 2. KFRT (chronic dialysis or kidney transplant); 3. Sustained GFR < 15 mL/min/1.73 m2; 4. Sustained GFR decline from baseline of ≥ 57%; 5 Sustained GFR decline from baseline of ≥ 50%; or 6. individual change from baseline to post-treatment eGFR if none of the outcomes occurred.
4. 4. Change in eGFR from following randomisation.
5. 5. Time to the first occurrence of any of the components of the composite of: 1) CV death 2) HF with and without hospitalisation 3) MI 4) Stroke

Investigational products

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

Test 3

Placebo 1

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 Clinical Study Information Center

Public contact point

Organisation

Astrazeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

15 EU/EEA countries · 180 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 153 files

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

Application history

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