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

NCT06217302 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: STUDY00000249
• Study Type: interventional
• Target: 150
• Locations: 2 countries
• Sites: 19

Brief Summary

Powerful new drugs that can prevent or delay end stage kidney disease (ESKD) - so called sodium-glucose cotransporter-2 inhibitors (SGLT2i) - are now available for patients with type 2 diabetes. Whether these drugs have similar effects in patients with type 1 diabetes (T1D) remains unknown because of the few studies in this population, due to concerns about the increase in risk of diabetic ketoacidosis (DKA, a serious, potentially fatal acute complication of diabetes due to the accumulation of substances called ketone bodies) observed with SGLT2i therapy in T1D. One of the few T1D studies conducted to date showed that implementing an enhanced DKA prevention plan can reduce the risk of DKA associated with the SGLT2i sotagliflozin (SOTA) to very low levels. In the present study, a similar DKA prevention program will be used to carry-out a 3-year trial to test the kidney benefit of SOTA in 150 persons with T1D and moderate to advanced DKD. After a 2-month period, during which diabetes care will be standardized and education on monitoring and minimizing DKA implemented, eligible study subjects will be randomly assigned (50/50) to take one tablet of SOTA (200 mg) or a similarly looking inactive tablet (placebo) every day for 3 years followed by 2-months without treatment. Neither the participants nor the study staff will know whether a person was assigned to taking SOTA or the inactive tablet. Kidney function at the end of the study will be compared between the two treatment groups to see whether SOTA prevented kidney function loss in those treated with this drug as compared to those who took the inactive tablet. The DKA prevention program will include participant education, close follow-up with study staff, continuous glucose monitoring, and systematic ketone body self-monitoring with a meter provided by the study. If successful, this study will provide efficacy and safety data that could be used to seek FDA approval of SOTA for the prevention of kidney function decline in patients with T1D and DKD.

Conditions

Diabetic Nephropathies; Kidney Failure, Chronic; Diabetes Mellitus Type 1; Heart Failure

Keywords

Diabetic Nephropathies; Kidney Failure, Chronic; Type 1 diabetes; Heart failure; Cardiovascular disease; Glomerular filtration rate; SGLT2 inhibitors; Diabetic kidney disease

Outcome Measures

Primary Outcomes (1)

• eGFR at the end of the wash-out period following the treatment period

  eGFR at the end of the 8-week drug washout period following the 3-year treatment period, estimated from Central Lab serum creatinine and cystatin C using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and adjusted by its baseline value. Baseline and end-of-washout eGFRs will be considered as the average of two eGFR values taken on two separate days before randomization (V2 and V4) and after the washout (V18 and V19), respectively.

  End of the 2-month wash-out period following the 3-year treatment period (weeks 162 and 164)

Secondary Outcomes (1)

• Time to ≥40% eGFR decline from baseline, kidney failure , or death from renal causes

  Up to the end of the 2-month wash-out period following the 3-year treatment period (week 0 to 164)

Other Outcomes (23)

• eGFR at the end of the 3-yr treatment period

  End of the 3-year treatment period (week 156)

• Time to fatal or non-fatal cardiovascular disease (CVD) events

  Up to the end of the 2-month wash-out period following the 3-year treatment period (week 0 to 164)

• Time to hospitalization or urgent visit for heart failure or CV death

  Up to the end of the 2-month wash-out period following the 3-year treatment period (week 0 to 164)

Study Arms (2)

Sotagliflozin

ACTIVE COMPARATOR

Oral sotagliflozin at a dose of 200 mg (one tablet) per day for three years followed by a 2-month wash-out period.

Drug: Sotagliflozin

Placebo

PLACEBO COMPARATOR

Oral tablets similar to sotagliflozin tablets but containing no active drug (one tablet per day for three years followed by a 2-month wash-out period).

Drug: Placebo

Interventions

Sotagliflozin DRUG

Oral sotagliflozin (200 mg per day)

Also known as: INPEFA

Sotagliflozin

Placebo DRUG

Inactive tablets identical to sotagliflozin tablets

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Type 2 diabetes or monogenic forms of diabetes or diabetes secondary to pancreatic disease;
• 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;
• 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 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);
• Use of anti tumor necrosis factor (TNF) alpha biologic medications at screening;
• 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;
• Blood beta-hydroxybutyrate (BHB) \>0.6 mmol/L for \>2 hours on \>2 occasions during the Run-in period;
• Inadequate beta hydroxybutyrate (BHB) testing (\<50% of the prescribed measurements) during Run-in;
• History of primary renal glycosuria;
• History of biopsy-proven non-diabetic chronic kidney disease (CKD);
• History of kidney transplant or currently on chronic dialysis;
• 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).

Sponsors & Collaborators

• Stanford University: collaborator
• Montefiore Medical Center: collaborator
• University of Toronto: collaborator
• University Health Network, Toronto: collaborator
• University of Calgary: collaborator
• University of Alberta: collaborator
• University of British Columbia: collaborator
• Institut de Recherches Cliniques de Montreal: collaborator
• LMC Diabetes & Endocrinology Ltd.: collaborator
• Alessandro Doria: lead
• The Cleveland Clinic: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator
• The Kidney Foundation of Canada: collaborator
• University of Michigan: collaborator
• University of Colorado, Denver: collaborator
• Northwestern University: collaborator
• Washington University School of Medicine: collaborator
• State University of New York - Upstate Medical University: collaborator
• Providence Medical Research Center: collaborator
• Joslin Diabetes Center: collaborator
• Lexicon Pharmaceuticals: collaborator
• DexCom, Inc.: collaborator
• University of Washington: collaborator
• Breakthrough T1D: collaborator
• AdventHealth: collaborator

Study Sites (19)

Stanford University Medical Center

Stanford, California, 94305, United States

RECRUITING

Barbara Davis Center / University of Colorado Denver

Aurora, Colorado, 80045, United States

RECRUITING

AdventHealth

Orlando, Florida, 32803, United States

RECRUITING

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

RECRUITING

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

RECRUITING

Albert Einstein College of Medicine / Montefiore Medical Center

The Bronx, New York, 10461, United States

RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

University of Texas Southwestern

Dallas, Texas, 75390, United States

RECRUITING

University of Washington

Seattle, Washington, 98105, United States

RECRUITING

Providence Sacred Heart Medical Center

Spokane, Washington, 99204, United States

RECRUITING

Unversity of Calgary

Calgary, Alberta, T2T 5C7, Canada

RECRUITING

Alberta Diabetes Institute

Edmonton, Alberta, T6G 2E1, Canada

RECRUITING

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

RECRUITING

LMC Diabetes and Endocrinology

Toronto, Ontario, M4G 3E8, Canada

RECRUITING

Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

RECRUITING

Institut de Recherches Cliniques de Montréal

Montreal, Quebec, H2W 1R7, Canada

RECRUITING

Related Publications (5)

• van Raalte DH, Bjornstad P, Persson F, Powell DR, de Cassia Castro R, Wang PS, Liu M, Heerspink HJL, Cherney D. The Impact of Sotagliflozin on Renal Function, Albuminuria, Blood Pressure, and Hematocrit in Adults With Type 1 Diabetes. Diabetes Care. 2019 Oct;42(10):1921-1929. doi: 10.2337/dc19-0937. Epub 2019 Aug 1.

  PMID: 31371432 BACKGROUND

• Bhatt DL, Szarek M, Pitt B, Cannon CP, Leiter LA, McGuire DK, Lewis JB, Riddle MC, Inzucchi SE, Kosiborod MN, Cherney DZI, Dwyer JP, Scirica BM, Bailey CJ, Diaz R, Ray KK, Udell JA, Lopes RD, Lapuerta P, Steg PG; SCORED Investigators. Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease. N Engl J Med. 2021 Jan 14;384(2):129-139. doi: 10.1056/NEJMoa2030186. Epub 2020 Nov 16.

  PMID: 33200891 BACKGROUND

• Bhatt DL, Szarek M, Steg PG, Cannon CP, Leiter LA, McGuire DK, Lewis JB, Riddle MC, Voors AA, Metra M, Lund LH, Komajda M, Testani JM, Wilcox CS, Ponikowski P, Lopes RD, Verma S, Lapuerta P, Pitt B; SOLOIST-WHF Trial Investigators. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. N Engl J Med. 2021 Jan 14;384(2):117-128. doi: 10.1056/NEJMoa2030183. Epub 2020 Nov 16.

  PMID: 33200892 BACKGROUND

• Markham A, Keam SJ. Sotagliflozin: First Global Approval. Drugs. 2019 Jun;79(9):1023-1029. doi: 10.1007/s40265-019-01146-5.

  PMID: 31172412 BACKGROUND

• Nardone M, Kugathasan L, Sridhar VS, Dutta P, Campbell DJT, Layton AT, Perkins BA, Barbour S, Lam TKT, Levin A, Lovblom LE, Mucsi I, Rabasa-Lhoret R, Rac VE, Senior P, Sigal RJ, Stanimirovic A, Persson F, Stougaard EB, Doria A, Cherney DZI. Modeling Cardiorenal Protection with Sodium-Glucose Cotransporter 2 Inhibition in Type 1 Diabetes: An Analysis of DEPICT-1 and DEPICT-2. Clin J Am Soc Nephrol. 2025 Apr 1;20(4):529-538. doi: 10.2215/CJN.0000000641. Epub 2025 Feb 7.

  PMID: 39918875 DERIVED

MeSH Terms

Conditions

Diabetic Nephropathies; Kidney Failure, Chronic; Diabetes Mellitus, Type 1; Heart Failure; Cardiovascular Diseases

Interventions

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Heart Diseases

Study Officials

• Alessandro Doria, MD PhD MPH

  Joslin Diabetes Center

  PRINCIPAL INVESTIGATOR

• Michael Mauer, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

• David Cherney, MD PhD

  University of Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christine Mendonca

CONTACT

617-334-2257; christine.mendonca@joslin.harvard.edu

Alexis Puthussery

CONTACT

617-975-8235; aputhuss@joslin.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior Investigator and Professor of Medicine

Study Record Dates

• First Submitted: January 9, 2024
• First Posted: January 22, 2024
• Study Start: October 31, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (13); CA (6)