Clinical trial NCT05405556: Sotagliflozin Safety and Tolerability Among Renal Transplant Recipients
Official title: Sotagliflozin Safety and Tolerability Among Renal Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Transplant
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2022-06-06
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A pre-defined algorithm for suggested management of acute changes in eGFR will be provided to all treating physicians. To test the proportion of patients successfully completing the protocol according to two different eGFR reporting strategies, randomization at the patient level will occur as follows:

1. only study-related eGFR values \>25% below baseline will be reported to patients and providers
2. all study-related eGFR values will be provided to patients and providers
Primary purpose: TREATMENT

Brief summary: This is an investigator-initiated, randomized controlled trial in adult KTRs (N=50) with stable allograft function to assess: 1) the reversibility of the expected acute changes in eGFR with sotagliflozin (donated by Lexicon); 2) proportion of patients completing the protocol according to different eGFR reporting strategies (using a predefined algorithm to manage the expected pharmacological effect of sotagliflozin on eGFR); 3) safety and tolerability of sotagliflozin.


Eligibility criteria: Inclusion Criteria:

* Adults ≥18 years
* Recipients of kidney transplant with stable eGFR\*
* eGFR-creatinine (CKD-EPI 2021) ≥25 mL/min/1.73 m2
* Informed consent

  * Stable eGFR will be ascertained by careful chart review establishing that the patient's current graft has been functioning for at least 12 months post-transplantation, patients have not been treated for acute rejection within the prior 3 months, and a creatinine-based eGFR is stable (two consecutive measurements separated by at least 28 days within 5 mL/min/1.73 m2) and ≥25 mL/min/1.73 m2.

Exclusion Criteria:

* Recurrent urinary tract infections (\>2 episodes/year or antibiotic prophylaxis)
* Biopsy-proven acute rejection within 12 weeks
* Screening serum potassium \>5.5 mmol/L
* Uncontrolled hypertension (systolic blood pressure \>180/100 mmHg)
* New York Heart Association (NYHA) Class IV HF
* Myocardial infarction, unstable angina, revascularization procedure (e.g., stent or bypass graft surgery), or cerebrovascular accident within 12 weeks
* History of diabetic ketoacidosis
* Type 1 Diabetes Mellitus
* Hereditary glucose-galactose malabsorption or primary renal glucosuria
* Liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis); Alanine aminotransferase (ALT) levels \>2.0 times the upper limit of normal (ULN) or total bilirubin \>1.5 times the ULN, unless consistent with Gilbert's disease
* Malignancy within 5 years (exceptions: squamous and basal cell carcinomas of the skin and carcinoma of the cervix in situ, or a malignancy that in the opinion of the investigator is considered cured with minimal risk of recurrence)
* Human immunodeficiency virus antibody positive
* Major surgery within 12 weeks
* Atraumatic amputation within past 12 months of screening, or an active skin ulcer, osteomyelitis, gangrene, or critical ischemia of the lower extremity within 6 months of screening
* Combination use of ACEi and ARB
* Current use of an SGLT2 inhibitor (within 12 weeks prior to randomization)
* Known allergies, hypersensitivity, or intolerance to SGLT2i or its excipients
* Digoxin plasma level \>1.2 ng/mL
* Clofibrate, fenofibrate, dronedarone, or ranolazine treatment that has not been at a stable dose in the 30 days prior to screening or randomization, or a dose adjustment is expected
* Received an active investigational drug (including vaccines) other than a placebo agent, or used an investigational medical device within 12 weeks before Day 1/baseline
* Pregnant or breast-feeding or planning to become pregnant or breast-feed during the study
* Women of childbearing potential not willing to use a highly-effective method(s) of birth control, or who are unwilling or unable to be tested for pregnancy
* Any condition that in the opinion of the investigator would make participation not in the best interest of the subject

Primary outcomes:
measure: Reversibility of eGFR changes
timeFrame: 16 weeks total
Secondary outcomes:
measure: Proportion of patients successfully completing the full treatment protocol, according to randomized groups
timeFrame: 16 weeks total
Other outcomes:
measure: Safety Assessments
timeFrame: 4 weeks
measure: Safety Assessments
timeFrame: 12 weeks
measure: Safety Assessments
timeFrame: Weeks 12-16 (off-drug)
measure: Safety Assessments
timeFrame: 12 weeks
measure: Safety Assessments
timeFrame: 12 weeks
measure: Safety Assessments
timeFrame: 12 weeks
measure: Safety Assessments
timeFrame: 12 weeks
measure: Safety Assessments
timeFrame: 12 weeks
measure: Safety Assessments
timeFrame: 12 weeks
measure: Safety Assessments
timeFrame: 12 weeks
measure: Safety Assessments
timeFrame: 12 weeks
measure: Safety Assessments
timeFrame: 12 weeks
measure: Tolerability Assessments
timeFrame: 12 weeks
measure: Tolerability Assessments
timeFrame: 12 weeks
measure: Tolerability Assessments
timeFrame: 12 weeks
Locations:
city: Boston
country: United States
facility: Brigham and Women's
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Martina M McGrath, MBBCh
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.