FINE-ONE: A landmark phase 3 clinical trial evaluating KERENDIA
in adults with CKD and T1D1,5

In FINE-ONE, a randomized, double-blind, placebo-controlled trial, the efficacy and safety of KERENDIA were evaluated when added
to a stable dose of an ACEi or ARB in adults with CKD associated with T1D1

Primary outcome: efficacy1

Change in UACR from baseline over 6 months (averaged over Months 3 and 6)1

KERENDIA improved renal outcomes and reduced UACR in adults with CKD associated with T2D in the FIDELIO-DKD and FIGARO-DKD studies. Therefore, the effect on UACR was used to infer a reduction in the risk of sustained eGFR decline and end-stage kidney disease in adults with CKD associated with T1D.1

Criteria and baseline characteristics

*For participants with an eGFR ≥25 to <60 mL/min/1.73 m2, starting dose was 10 mg od. For participants with an eGFR ≥60 mL/min/1.73 m2, starting dose was 20 mg od. Up-titration
from 10 mg to 20 mg was permitted from Month 1 onward based on serum potassium and eGFR. Dose reduction was allowed at any time for safety reasons.1,5 †Patients were required
to be taking a stable dose of an ACEi or ARB as standard of care.1

ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor blocker; CKD=chronic kidney disease; eGFR=estimated glomerular filtration rate; R=randomization; T1D=type 1 diabetes; T2D=type 2 diabetes; UACR=urine albumin-to-creatinine ratio.

Trial Design UACR Safety

FIGARO-DKD and FIDELIO-DKD shared similar designs1,2,19,28,29

*On top of maximum-tolerated dose of either ACEi or ARB.2,28 †Up-titration of study drug was encouraged after visit 2, provided potassium value was ≤4.8 mEq/L and eGFR was stable; down-titration was allowed any time after treatment initiation for safety reasons.29,30 ‡The purpose of the mandatory run-in period was to allow for optimization of participant standard-of-care medical therapies. This included ensuring that a patient was pretreated with a maximum-tolerated labeled dose of either an ACEi or an ARB (preferably without dose adjustments or switching to a different ACEi or ARB) for >4 weeks prior to the screening visit.29,30 §Visits at month 1, month 4, and every 4 months thereafter.2,28 II4 weeks and 5 days after last dose.29,30

ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor blocker; CKD=chronic kidney disease; CV=cardiovascular; eGFR=estimated glomerular filtration rate; T2D=type 2 diabetes.

Key criteria and baseline characteristics

Select inclusion criteria12

  • Age ≥18 years
  • Type 1 diabetes
  • Continuously treated with insulin
  • HbA1c at screening <10.0%​
  • UACR ≥200-<5000 mg/g​
  • eGFR ≥25-<90 mL/min/1.73 m²​
  • On a stable dose of ACEi or ARB​
  • Serum potassium level ≤4.8 mEq/L​

Select exclusion criteria12

  • Mean BP >160/100 mmHg or mean systolic BP <90 mmHg at screening​
  • Hospitalization due to a CV event ≤4 weeks prior to screening​
  • Symptomatic heart failure with reduced ejection fraction with class 1A indications for MRAs​​
  • Current or previous (≤8 weeks prior to screening) treatment with a SGLT-2/1i
    or GLP-1RA​​

Select baseline characteristics13

  • Mean age: 51.6 ± 13.7​
  • Male: 65.3%​
  • BMI, kg/m2, mean ± SD: 27.6 ± 6.0​
  • Systolic BP, mmHg: 135.2 ± 16.7​
  • eGFR, mL/min/1.73 m2, mean ± SD: 58.8 ± 19.1​
  • UACR, mg/g, median (IQR): 549.0 (298.8-1190.7)​
  • Serum [K+], mEq/L, mean: 4.6 ± 0.4​
  • HbA1c, %, mean*: 7.6 ± 1.1
  • Duration of diabetes, years, mean: 32.0 ± 14.2​
  • CVD†: 24.4%​​
  • Hypertension: 85.5%​
  • ACEi or ARBs: 99.2%
  • Diuretics: 36.0%
  • Beta blockers: 27.3%​
  • Statins: 73.6%​
  • Platelet aggregation inhibitors‡: 31.4%

Renal outcomes trial1,28

FIDELIO-DKD (N=5674)

  • Primary composite renal endpoint
  • Secondary composite CV endpoint

Select inclusion criteria1

UACR of 30 to <300 mg/g, eGFR of 25 to <60 mL/min/1.73 m2,
and diabetic retinopathy or UACR of ≥300 mg/g and eGFR of 25 to <75 mL/min/1.73 m2

Select exclusion criteria1

Other conditions:

  • Symptomatic chronic HF with reduced ejection fraction (NYHA class II-IV)
  • Known significant nondiabetic kidney disease

Select baseline characteristics28

  • Median UACR of 852 mg/g
  • Mean eGFR of 44.3 mL/min/1.73 m2

*Values missing for 2 participants.13 †History of CVD was determined by the presence of one of the following in the medical history: myocardial infarction, coronary artery stenosis, cerebrovascular accident, transient ischaemic attack, peripheral arterial occlusive disease or cardiac failure.13​ ‡Excluding heparin.13​​

ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor blocker; BMI=body mass index; BP=blood pressure; CV=cardiovascular;
CVD=cardiovascular disease; eGFR=estimated glomerular filtration rate; GLP-1RA=glucagon-like peptide-1 receptor agonist; HbA1c=glycated hemoglobin; IQR=interquartile range; [K+]=potassium concentration; MRA=mineralocorticoid receptor antagonist; SD=standard deviation;​ SGLT-2/1i=sodium-glucose cotransporter-2/1 inhibitor; UACR=urine albumin-to-creatinine ratio.​​

KERENDIA for CKD associated with T2D:
efficacy and safety overview

FIGARO-DKD1,2

13%RRR

Primary CV composite endpoint1,2

On top of standard of care, 13% RRR vs placebo, HR=0.87 (95% CI: 0.76-0.98), P=0.026

32%placebo-
corrected RR

Exploratory analysis1

UACR reduction relative to placebo on top of standard of care: 32%
(95% CI: 30-35%), at month 4

Secondary renal composite endpoint1,2

The key secondary composite of kidney failure, sustained eGFR decline of ≥40%, or renal death occurred in 350 patients in the KERENDIA group (9.5%) and 395 patients in the placebo group (10.8%) (HR=0.87 [95% Cl: 0.76-1.01]). The difference was not statistically significant

FIDELIO-DKD1

18%RRR

Primary renal composite endpoint1

On top of standard of care, 18% RRR vs placebo, HR=0.82 (95% CI: 0.73-0.93), P=0.001

31%placebo-
corrected RR

Exploratory analysis1

UACR reduction relative to placebo on top of standard of care: 31%
(95% CI: 29-34%), at month 4

14%RRR

Secondary CV composite endpoint1

On top of standard of care, 14% RRR vs placebo, HR=0.86 (95% CI: 0.75-0.99), P=0.034

Safety: pooled data FIGARO-DKD and FIDELIO-DKD1

Adverse reactions reported in ≥1% of patients taking KERENDIA and more common than placebo

Hyperkalemia:
14% (KERENDIA: n=912/6510)
vs 6.9% (placebo: n=448/6489)

Hypotension:
4.6% (KERENDIA: n=302/6510)
vs 3.0% (placebo: n=194/6489)

Hyponatremia:
1.3% (KERENDIA: n=82/6510)
vs 0.7% (placebo: n=47/6489)

CI=confidence interval; CKD=chronic kidney disease; CV=cardiovascular; eGFR=estimated glomerular filtration rate; HR=hazard ratio; RR=relative reduction; RRR=relative risk reduction; T2D=type 2 diabetes; UACR=urine albumin-to-creatinine ratio.