Sotagliflozin Safety and Tolerability Among Renal Transplant Recipients

NCT05405556 | Completed Phase 2 FDA Drug

• 1 other identifier: 2022P000454
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Kidney Transplant

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Proportion of patients successfully completing the full treatment protocol, according to randomized groups

  16 weeks total

Other Outcomes (15)

• Safety Assessments

  4 weeks

• Safety Assessments

  12 weeks

• Safety Assessments

  Weeks 12-16 (off-drug)

Study Arms (2)

Patients and providers only aware of study eGFR values more than 25% below baseline

EXPERIMENTAL

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

Patients and providers aware of all study eGFR values

OTHER

All study-related eGFR measurements will be reported to the treating physician and patient.

Diagnostic Test: eGFR reporting

Interventions

eGFR reporting DIAGNOSTIC_TEST

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

Patients and providers aware of all study eGFR values; Patients and providers only aware of study eGFR values more than 25% below baseline

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Martina McGrath, MD: lead

Study Sites (1)

Brigham and Women's

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• 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

Study Officials

• Martina M McGrath, MBBCh

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Physician, Instructor in Medicine, Principal Investigator

Model Details: 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

Study Record Dates

• First Submitted: May 20, 2022
• First Posted: June 6, 2022
• Study Start: October 17, 2022
• Primary Completion: May 10, 2024
• Study Completion: November 16, 2024
• Last Updated: February 5, 2025

Record last verified: 2024-11

Locations

US (1)