Precision T1D Platform - New Therapies for Cardio-Renal Complications

Accelerating Breakthrough Targeted New Therapies for Cardio-Renal Complications in People With T1D (Precision T1D Platform)

Breakthrough T1D has awarded support for a joint University of Michigan-Oregon Health & Science University Center of Excellence (CoE) to address cardio-renal complications in T1D. The overarching hypothesis of the CoE is that individuals with T1D have unique endophenotypes determining their progression towards cardio-renal end organ damage. Defining the underlying molecular programs in T1D endophenotypes provides the rationale for testing existing or new drug candidates in mechanistic trials targeting T1D cardio-renal complications by matching endophenotypes to targeted therapies.

Study Overview

• Status: Not yet recruiting
• Conditions: Type 1 Diabetes; T1D Diabetic Chronic Kidney Disease; T1D Heart Failure; Cardio-renal Vascular Function and Failure
• Intervention / Treatment: Drug: Finerenone; Drug: Sotagliflozin

Detailed Description

This is a multicenter, open label pilot platform study to evaluate the impact of allocating patients with T1D and early signs of HF/DKD to targeted therapies based on their disease pathway activation signatures. The hypothesis is that stratifying T1D patients by molecularly-defined endophenotypes enables the use of targeted therapies that can more effectively prevent or slow cardio-renal complications.

There is no randomized allocation to treatment arms; rather, the eligible participant's clinical and biomarker data will be reviewed by the Molecular T1D Board (see section XX) which will adjudicate each participant to a treatment arm based on their based on their disease pathway activation signatures. Activation of different treatment arms may be initiated at different time points during the study.

The following sections describe the master protocol, outlining the requirements across all treatment arms, including the study-wide inclusion and exclusion criteria and study-wide procedures. Appendix A outlines any treatment arm/investigational agent specific information, including defining additional treatment-specific eligibility criteria and required study procedures.

The study schema can be found in Section 1.2 and the Schedule of Activities (SoA) in Section 1.3. Potential participants will undergo a two-part consent and screening process. The initial consent and screening visit will be limited to activities necessary for assessment by the Molecular T1D Board. Following review by the Molecular T1D Board, participants will be adjudicated to one treatment arm. At this time, participants will undergo the second consent and screening step, which will include information about specific requirements for their assigned investigational arm and, if in agreement, a complete eligibility assessment via a full screening visit. If the participant is deemed eligible, they will be notified and investigational product will be mailed to them directly. The screening visit results will also serve as the baseline results provided the first dose of study drug is taken within 14 (target) to 21 (limit) days of the screening visit. If more than 21 days, a retest of all laboratory measures will be performed.

Participants will receive open label treatment for 26 weeks, with planned study visits at weeks 2, 6, 12, 26, 30, 48, and 72. The total study duration of participation will be up to 78 weeks, inclusive of screening and follow-up visits. Participants will be enrolled in this study at Oregon Health and Science University and the University of Michigan.

The currently planned number of study arms is three, with 15-19 participants enrolled in each arm. The study sponsors will have the option to increase the number of study arms and potential targeted therapies, which would be documented in the appendices and this master protocol.

• Study Type: Interventional
• Enrollment (Estimated): 57
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Laura Nguyen; Phone Number: (971) 509-4222; Email: nguyelau@ohsu.edu
• Study Contact Backup: Name: Aly Carlson; Phone Number: (971) 610-3005; Email: carlsaly@ohsu.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
      • Sub-Investigator: Matthias Kretzler, MD
      • Contact: Hailey Desmond, MS; Phone Number: (734) 764-6955; Email: heturner@med.umich.edu
      • Principal Investigator: Lynn Ang, MD
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
      • Principal Investigator: Rodica Busui, MD, PhD
      • Sub-Investigator: Brian Davidson, MD
      • Contact: Laura Nguyen; Phone Number: 971-509-4222; Email: nguyelau@ohsu.edu
      • Contact: Aly Carlson; Phone Number: 971-610-3005
      • Sub-Investigator: Jonathan Purnell, MD
      • Sub-Investigator: David Ellison, MD
      • Sub-Investigator: Kristin Childress, MD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of T1D, defined as hyperglycemia requiring treatment with insulin within one year from diagnosis or, if the onset was after age 35 years, documentation of the presence of hyperglycemia and one or more of the following:

   1. presence of circulating T1D-associated autoantibodies, or
   2. history of hospitalization for diabetic ketoacidosis, or
   3. documented plasma C-peptide below the limit of detection with standard assay (with concurrent blood glucose >100 mg/dL)
2. Aged 18-75 years, inclusive
3. T1D duration >10 years
4. HbA1c: 7-10%

5. Meets one of the following, either

   1. UACR > 30 mg/dl with eGFR ≥ 60mL/min/1.73 m2 and receiving standard of care therapy for early DKD Stage 2, including renin angiotensin system blockade (RASB), unless contraindicated or not tolerated, or
   2. Early (Stage B HF) defined as NT-proBNP > 125 pg/mL
6. Willing and able to adhere to schedule of activities and protocol requirements, including written informed consent

Exclusion Criteria:

1. Diagnosis of Type 2 diabetes or monogenic forms of diabetes or diabetes secondary to pancreatic disease
2. Use of any active platform study therapies outside study assignment within 2 months prior to screening. See Appendix A for active therapy arms.:
3. Use of GLP-1 receptor agonists if in use for less than 1 month and/or not on stable dose for at least 2 weeks at screening
4. Use of aldosterone inhibitors within 2 months prior to screening
5. Immunosuppressive medications within 3 months prior to screening
6. Systolic BP>160 or diastolic BP >95 mmHg at screening
7. History of ≥3 severe hypoglycemic events requiring third-party assistance for correction within 3 months prior to screening

8. Evidence of either of the following:

   1. History of diabetic ketoacidosis (DKA) or non-ketotic hyperosmolar state within 3 months prior to screening, or
   2. >1 episode of DKA or non-ketotic hyperosmolar state within 12 months prior to screening
9. Serum potassium > 5 mmol/L at screening
10. Absolute neutrophil count < 2.0 × 109 per L at screening
11. Platelet count < 120 × 109 per L at screening
12. Known active tuberculosis, HIV, or hepatitis B or C at screening
13. 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 AST or ALT >2 times upper limit of normal, and/or total bilirubin >1.3 times upper limit of normal at screening
14. History of severe acquired immune deficiency syndrome or severely immunocompromised status in the opinion of the investigator
15. History of biopsy-proven non-diabetic CKD
16. History of any other cause of HF (viral, congenital, valvular)
17. History of heart or renal transplant or currently on chronic dialysis
18. Cancer treatment, excluding non-melanoma skin cancer treated by excision, carcinoma in situ of the cervix or uterus, ductal breast cancer in situ, resected non-metastatic breast or prostate cancer, within one year prior to screening
19. Illicit drug abuse within 6 months prior to screening in the opinion of the investigator
20. Current heavy alcohol use (for men, ≥5 drinks on any day or ≥15 drinks per week; for women, ≥4 drinks on any day or ≥8 drinks per week)
21. Participation in another interventional clinical research study within 30 days prior to screening
22. Breastfeeding, pregnancy, or unwillingness to be on contraception during the trial
23. Presence of a clinically significant medical history, physical examination, laboratory finding or other investigator concern that may interfere with any aspect of study conduct or interpretation of results

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: Finerenone; Study participants with biomarker profiles showing a match for finerenone will be adjudicated to this treatment arm. The clinically recommended dose for finerenone based on manufacturer guidelines is 20 mg once daily (oral) if screening eGFR is ≥60 mL/min/1.73 m2.	Drug: Finerenone; Each treatment arm will be a different unique drug. There will be no crossing over of participants between arms. Each participant that is adjudicated to their treatment arm will remain on that arm for the duration of the study through study completion.; Other Names: KERENDIA
Experimental: Sotagliflozin; Study participants with biomarker profiles that match with sotagliflozin will be adjudicated to this treatment arm. The clinically recommended dose of sotagliflozin is 200 mg per the manufacturer guidelines. The dose of 200 mg has a lower DKA risk and similar kidney benefits to the higher doses.	Drug: Sotagliflozin; Each treatment arm will be a different unique drug. There will be no crossing over of participants between arms. Each participant that is adjudicated to their treatment arm will remain on that arm for the duration of the study through study completion.; Other Names: INPEFA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Markers of Renal Health [Safety and Tolerability]	The primary efficacy endpoints are measures of early (week 26) outcomes on markers of renal health, defined as the percent change from baseline to week 26 in UACR.	26 weeks
Markes of Cardio Health [Safety and Tolerability]	The primary efficacy endpoints are measures of early (week 26) outcomes on markers of cardio health as defined by the percent change from baseline to week 26 in NT-proBNP.	26 weeks
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	The primary safety endpoints are defined as incidence of serious adverse events, adverse events and clinically significant abnormal laboratory tests.	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immediate Outcomes of Renal Health (week 6)	The secondary endpoints are measures of immediate outcomes on markers of renal health as defined by changes from baseline to week 6 in UACR.	20 weeks
Immediate Outcomes of Cardio Health (week 6)	The secondary endpoints are measures of immediate outcomes on markers of cardio health as defined by changes from baseline to week 6 in NT-proBNP.	20 weeks
Immediate (week 6) and Early (week 26) Outcomes of Nephron Function Failure	The secondary endpoints are measures of immediate outcomes on markers of renal function failure as defined by changes from baseline to week 6 and from baseline to week 26 in eGFR.	26 weeks

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: University of Michigan; Breakthrough T1D
• Investigators: Study Chair: Rodica Busui, MD, PhD, Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: May 11, 2026
• First Posted (Actual): May 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Heart Failure; Type 1 Diabetes; T1D; Platform Trial; DKD; Diabetic Chronic Kidney Disease
• Additional Relevant MeSH Terms: Endocrine System Diseases; Cardiovascular Diseases; Heart Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Heart Failure; Diabetes Mellitus, Type 1; (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol; finerenone
• Other Study ID Numbers: 30027

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: A limited dataset along with other study related materials (i.e., protocol, consent template, etc.) will be shared with other researchers/investigators at other institutions such as the University of Michigan via a data use agreement initiated by the primary site, Oregon Health & Science University.
• IPD Sharing Time Frame: The sharing of information will be available as soon as both institutions sign the data use agreement for a limited dataset. However, the sharing of protocols and consent form language are currently being shared as both institutions are collaborating to draft these documents. This collaborating is facilitated by a subaward contract between two institutions.
• IPD Sharing Access Criteria: Only study personnel working on the study will have access to study related information. All information is kept on secure share drives at each respective institution and access is only possible if the personnel is an employee with institutional specific credentials to securely log in.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

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.: Yes