Sotagliflozin to Slow Kidney Function Decline in Persons With Type 1 Diabetes and Diabetic Kidney Disease

Ki vehet részt

• Type1 diabetes (T1D) continuously treated with insulin within one year from diagnosis
• Duration of T1D ≥ 8 years
• eGFR based on serum creatinine and cystatin c (2021 serum creatinine-cystatin C CKD-EPI equation) between 20 and 60 ml/min/1.73 m2 at screening (with the option of a second eGFR measurement within 4 weeks from the first one if the eGFR was in the range of >60 to ≤65 or ≥16 to <20 ml/min/1.73 m2)
• a. First morning void urinary albumin creatinine ratio (UACR) ≥200 mg/g at Screening or on repeat measurement within 4 weeks from the first one, or b. First morning void urinary UACR ≥100 mg/g at Screening or on repeat measurement within 4 weeks and at least one uACR >=30 in the previous 2 years while treated with RASB at a stable dose
• HbA1c at screening <10% (with the option of a second HbA1c measurement within 4 weeks from the first one if the HbA1c was ≤10.2%)
• Receiving standard of care, including renin angiotensin system blockers (RASB) at a clinically appropriate dose, unless contraindicated or not tolerated
• Willing and able to comply with schedule of events and protocol requirements, including written informed consent, and willing to wear a continuous glucose monitoring (CGM) device for the entire duration of the study
• a. Blood pressure ≤155/95 mmHg at screening, or b. BP ≤155/95 mmHg at the end of the run-in period, or c. consistent BP ≤155/95 mmHg on home monitoring during the run-in period, as determined by study site investigator, despite BP values >155/95 mmHg in clinic

Ki nem vehet részt

• Use of any SGLT inhibitor in the previous 2 months
• Use of dual medication RASB therapy (spironolactone, eplerenone, finerenone are allowed in combination with RASB therapy)
• Use of anti tumor necrosis factor (TNF) alpha biologic medications at screening
• History of kidney transplant or currently on chronic dialysis
• Illicit drug abuse within 6 months of screening
• Type 2 diabetes or monogenic forms of diabetes or diabetes secondary to pancreatic disease
• Known allergies, hypersensitivity, or intolerance to SOTA
• History of ≥3 severe hypoglycemic events (requiring third-party assistance for correction) within 3 months of screening
• History of diabetic ketoacidosis (DKA) or non-ketotic hyperosmolar state within 3 months of screening OR >1 episode of DKA or non-ketotic hyperosmolar state within 12 months of screening
• History of primary renal glycosuria
• History of biopsy-proven non-diabetic chronic kidney disease (CKD)
• History of severe acquired immune deficiency syndrome or human immunodeficiency virus (HIV) infection or severely immunocompromised status
• Cancer treatment (excluding non-melanoma skin cancer treated by excision, carcinoma in situ of the cervix or uterus, ductal breast cancer in situ, resected non-metastatic breast or prostate cancer) within one year of screening
• Any condition that may render the patient unable to comply with study requirements and/or complete the study
• Use of GLP-1 receptor agonists and other non-insulin glucose-lowering agents if not on stable dose for > 2 months at screening (patients can be rescreened after being on stable dose for > 2 months)
• Blood beta-hydroxybutyrate (BHB) >0.6 mmol/L for >2 hours on >2 occasions during the Run-in period
• Current or past history of decompensated cirrhosis (defined as variceal bleeding, ascites or hepatic encephalopathy), and/or known diagnosis of cirrhosis based on liver biopsy, imaging, or elastography, and/or aspartate aminotransferase (AST) or alanine transaminase (ALT) at screening >2 times upper limit of normal, and/or total bilirubin at screening >1.3 times upper limit of normal)
• Presence of a clinically significant medical history, physical examination, or laboratory finding that may interfere with any aspect of study conduct or interpretation of results
• Use of automated insulin delivery devices that are not approved by health regulatory agencies, or used in ways that do not align with manufacturer recommendations
• Inadequate beta hydroxybutyrate (BHB) testing (<50% of the prescribed measurements) during Run-in
• Heavy alcohol use (for men, 5 drinks or more on any day or 15 drinks or more per week; for women, 4 drinks or more on any day or 8 drinks or more per week)
• Participation in another interventional clinical research study within 30 days of screening
• Breastfeeding, pregnancy, or unwillingness to be on contraception during the trial