Sotagliflozin Safety and Tolerability Among Renal Transplant Recipients (START)

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.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant
• Intervention / Treatment: Diagnostic test: eGFR reporting

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients and providers only aware of study eGFR values more than 25% below baseline; Any study-related eGFR value more than 25% below the baseline measurement will be reported to the patient and treating physician.	Diagnostic test: eGFR reporting; To test the proportion of patients successfully completing the protocol according to different eGFR reporting strategies, randomization in a 1:1 fashion at the patient level (n=50) will occur as follows: only study-related eGFR values >25% below baseline will be reported to patients and providers; all study-related eGFR will be provided to patients and providers
Other: Patients and providers aware of all study eGFR values; All study-related eGFR measurements will be reported to the treating physician and patient.	Diagnostic test: eGFR reporting; To test the proportion of patients successfully completing the protocol according to different eGFR reporting strategies, randomization in a 1:1 fashion at the patient level (n=50) will occur as follows: only study-related eGFR values >25% below baseline will be reported to patients and providers; all study-related eGFR will be provided to patients and providers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reversibility of eGFR changes	Following 12 weeks of open-label drug treatment, participants will stop drug and be followed for a further four weeks (16 weeks total). Reversibility will be assessed as the proportion of patients who return to baseline eGFR (+/- 10%) by the end of the 4-week off-treatment period.	16 weeks total

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients successfully completing the full treatment protocol, according to randomized groups	Following 12 weeks of open-label drug treatment, participants will stop drug and be followed for a further four weeks. The proportion of patients completing the full 16 weeks will be compared according to randomized groups.	16 weeks total

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Assessments	- Acute changes in eGFR (baseline to 4 weeks)	4 weeks
Safety Assessments	- Longer-term changes in eGFR (baseline to 12 weeks and 4 weeks to 12 weeks)	12 weeks
Safety Assessments	- Reversibility of changes in eGFR (12 to 16 weeks - after drug discontinuation)	Weeks 12-16 (off-drug)
Safety Assessments	- Acute Kidney Injury (>50% increase in serum creatinine/40% decline in eGFR within one week), which will be assessed throughout the on-drug period of 12 weeks	12 weeks
Safety Assessments	- All adverse events (AEs)	12 weeks
Safety Assessments	- All serious adverse events (SAEs)	12 weeks
Safety Assessments	- Diarrhea	12 weeks
Safety Assessments	- Infection requiring treatment with anti-microbials (including urogenital infection and urinary tract infections)	12 weeks
Safety Assessments	- Severe hypoglycemia (event that requires assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions)	12 weeks
Safety Assessments	- Diabetic ketoacidosis	12 weeks
Safety Assessments	- Hyperkalemia (>5.5 mmol/L)	12 weeks
Safety Assessments	- Hypotension (symptomatic SBP <90 mmHg or hypotension requiring adjustment in blood pressure medications or treatment in an emergency or hospitalized setting)	12 weeks
Tolerability Assessments	- Proportion of participants able to complete the full 12 weeks of treatment, according to randomized arm	12 weeks
Tolerability Assessments	- Study medication discontinuation rates	12 weeks
Tolerability Assessments	- KDQOL-36 questionnaire	12 weeks

Collaborators and Investigators

• Sponsor: Martina McGrath, MD
• Investigators: Principal Investigator: Martina M McGrath, MBBCh, Brigham and Women's Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2022
• Primary Completion (Actual): May 10, 2024
• Study Completion (Actual): November 16, 2024

Study Registration Dates

• First Submitted: May 20, 2022
• First Submitted That Met QC Criteria: June 1, 2022
• First Posted (Actual): June 6, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 3, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 2022P000454

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Only sharing of anonymized data will be considered as per approved protocol. Written requests for data sharing will be considered on a case-by-case basis from qualified external researchers, based on scientific merit.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No