A Study to Understand the Genetics and Clinical Course of Focal Segmental Glomerulosclerosis (FSGS), Treatment-Resistant Minimal Change Disease (TR-MCD), and Diabetic Nephropathy (DN)

Study Overview
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Brief Summary
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This is a study with 2 parts. Part 1 comprises a visit to collect biological samples necessary for the molecular characterization of chronic kidney disease. Part 2 comprises an observational period of 5 visits over a period up to 8 weeks. During Part 2, baseline tests will be conducted, and urine will be collected approximately every 2 weeks for 8 weeks. Patients may participate in Part 1, Part 2, or both, and will be followed for up to 1 year consisting of data collection from the patient's medical records and home collection of urine samples every 4 months.

Official Title
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A Study to Characterize the Genetic, Biomarker, and Clinical Profile of Patients With Focal Segmental Glomerulosclerosis (FSGS), Treatment-Resistant Minimal Change Disease (TR-MCD), and Diabetic Nephropathy (DN)

Conditions
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Glomerulosclerosis, Focal Segmental, Minimal Change Disease, Diabetic Nephropathies

Intervention / Treatment
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* Other: FSGS/TR-MCD
* Other: Diabetic Nephropathy (DN)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For FSGS/TR-MCD patients : Competent and willing to provide informed consent and adhere to all study assessments and restrictions. Male or female ≥ 18 years of age with FSGS or TR-MCD at the time of providing written informed consent. Diagnosis of FSGS or TR-MCD, based on either biopsy or genetic testing. Urinary protein to creatinine ratio (UPCR) ≥ 1.0 g/g. Estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2. For DN patients: Competent and willing to provide informed consent and adhere to all study assessments and restrictions. Male or female ≥ 18 years of age with DN at the time of providing written informed consent. Diagnosis of type 2 diabetes Urinary albumin to creatinine ratio (UACR) ≥ 150 mg/g. Estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2. Exclusion Criteria: For FSGS/TR-MCD patients: Evidence of another kidney disease or kidney disease secondary to an infectious process. History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. Patients whose results are compatible with prior immunization or treatment may be included. Body mass index (BMI) > 42 kg/m2. Significant history or evidence of clinically significant disorder, condition, current illness, or disease that, in the opinion of the Investigator, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion (eg, severe cardiac disease, cardiac conduction defect, or severe or chronic hepatobiliary disease). History of malignancy not in remission within the last 5 years other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma in situ. History of any organ or bone marrow transplant, including kidney grafts. History of alcoholism or drug/chemical abuse within 12 months. Preplanned surgery or procedures that would interfere with the conduct of the study. For DN patients: Evidence of another kidney disease or kidney disease secondary to an infectious process. History of HIV, hepatitis B, or hepatitis C. Patients whose results are compatible with prior immunization or treatment may be included. BMI > 42 kg/m2. Significant history or evidence of clinically significant disorder, condition, current illness, or disease that, in the opinion of the Investigator, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion (eg, severe cardiac disease, cardiac conduction defect, or severe or chronic hepatobiliary disease). History of malignancy not in remission within the last 5 years other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma in situ. History of any organ or bone marrow transplant, including kidney grafts. History of alcoholism or drug/chemical abuse within 12 months. Preplanned surgery or procedures that would interfere with the conduct of the study. Renal disease that requires immunosuppressive therapy (currently, or in the past).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| FSGS/TR-MCD<br>Patients with FSGS/TR-MCD | Other: FSGS/TR-MCD<br>* This is a non-interventional study<br>|
| Diabetic Nephropathy (DN)<br>Patients with DN | Other: Diabetic Nephropathy (DN)<br>* This is a non-interventional study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Urine Protein-to-Creatinine Ratio (UPCR) |  | Approximately 1 year | 
| Change in Urine Albumin-to-Creatinine Ratio (UACR) |  | Approximately 1 year | 
| Estimated Glomerular Filtration Rate (eGFR) |  | Baseline/Biomarker collection visit | 
| Change in Estimated Glomerular Filtration Rate (eGFR) |  | Approximately 8 weeks | 
| Change in Urine Biomarker: Nephrin |  | Approximately 1 year | 
| Change in Urine Biomarker: Podocin |  | Approximately 1 year | 
| Change in Urine Biomarker: Rac1 |  | Approximately 1 year | 
| Change in Urine Biomarker: Synaptopodin |  | Approximately 1 year | 
| Change in Urine Biomarker: Urea |  | Approximately 1 year | 
| Change in Urine Biomarker: Other Exploratory |  | Approximately 1 year | 
| Change in Serum/Plasma Biomarker: Other Exploratory |  | Approximately 8 weeks | 
| Number of patients with genetic variants predicted to be associated with chronic kidney disease and functional consequence | DNA analysis of blood sample | Baseline/Biomarker collection visit | 
| Gene expression profile and phenotype of inducible pluripotent stem cell (iPSC)-generated organoids | Generation of iPSC from whole blood sample | Baseline/Biomarker collection visit | 
| Change from Baseline Patient-reported Assessment of FSGS Symptoms | FSGS/TR-MCD patients will assess disease symptomatology utilizing the FSGS Symptom Diary and FSGS Symptom Impact Questionnaire | Approximately 8 weeks | 
| Change from Baseline Patient-reported Assessment of Health Status | Patients will assess health status using the 36-Item Short Form Health Survey (SF-36) | Approximately 8 weeks | 
| Change from Baseline Patient-reported Assessment of Fatigue | Patients will assess the symptom of fatigue utilizing the Modified Fatigue Impact Scale | Approximately 8 weeks | 
| Change from Baseline Clinician-reported Assessment of Edema | Clinicians will assess edema in FSGS/TR-MCD patients using a standardized measurement of edema in FSGS/TR-MCD patients | Approximately 8 weeks | 
| Incidence of Untoward Medical Occurrences | Incidence of untoward medical occurrences that result in death; are life threatening; require inpatient hospitalization or prolongation of existing hospitalization; result in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; or result in an important medical event. | Approximately 1 year | 
| % of Patients with Change in Treatment | Change in treatment as indicated by patient medical record | Approximately 1 year |