Sotagliflozin to Slow Kidney Function Decline in Persons With Type 1 Diabetes and Diabetic Kidney Disease
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-75
SponsorAlessandro Doria
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
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);
Trial design
Design model
Parallel
Treatments tested in this trial
Sotagliflozin
DrugOral sotagliflozin (200 mg per day)
Placebo
DrugInactive tablets identical to sotagliflozin tablets
Treatment groups
150 Participants
are divided into 2 treatment groupsGroup A: SotagliflozinActive comparator 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
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.
Time frame
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
Time from randomization to 1. sustained ≥40% eGFR decline (based on eGFR estimated from serum creatinine and cystatin C using the 2021 CKD-EPI equation) confirmed after 30 days; 2. kidney failure, defined by eGFR ≤10ml/min/ 1.73m2 confirmed after 30 days or occurring within 30 days prior to death, or initiation of maintenance kidney replacement therapy; or 3. death from kidney-related causes. If an eGFR value meeting the above criteria is observed at the last study visit or immediately before a participant is lost to follow-up or withdraws from the study, no confirmation of this value will be necessary.
Time frame
Up to the end of the 2-month wash-out period following the 3-year treatment period (week 0 to 164)Other outcomes
1
eGFR at the end of the 3-yr treatment period
eGFR at the end of the 3-yr treatment period (before the washout period) adjusted for the baseline value
Time frame
End of the 3-year treatment period (week 156)2
Time to fatal or non-fatal cardiovascular disease (CVD) events
Time to fatal or non-fatal CVD events (CV death, non-fatal myocardial infarction, non-fatal stroke, or coronary, carotid, or peripheral revascularization procedures)
Time frame
Up to the end of the 2-month wash-out period following the 3-year treatment period (week 0 to 164)3
Time to hospitalization or urgent visit for heart failure or CV death
Time to hospitalization or urgent visit for heart failure or death for cardiovascular causes
Time frame
Up to the end of the 2-month wash-out period following the 3-year treatment period (week 0 to 164)4
Time to hospitalization for heart failure
Time to hospitalization for heart failure
Time frame
Up to the end of the 2-month wash-out period following the 3-year treatment period (week 0 to 164)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Alessandro Doria
Lead sponsor
Joslin Diabetes Center
Sponsor institution
Canadian Institutes of Health Research (CIHR)
Collaborator
The Kidney Foundation of Canada
Collaborator
The Cleveland Clinic
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
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
Joslin Diabetes Center
Collaborator
Lexicon Pharmaceuticals
Collaborator
DexCom, Inc.
Collaborator
University of Washington
Collaborator
Breakthrough T1D
Collaborator
AdventHealth
Collaborator
Source ClinicalTrials.gov