Diabetes Complications, Diabetes Mellitus, Diabetic Nephropathies, Endocrine System Diseases, Glomerulonephritis, Glomerulosclerosis, Focal Segmental, Kidney Diseases, Nephritis, Nephrosis, Nephrosis, Lipoid, Urologic Diseases
Conditions
Brief summary
This is a phase 2a study evaluating the safety and tolerability of multiple ascending doses of GFB-887 in patients with diabetic nephropathy (DN), focal segmental glomerulosclerosis (FSGS), and treatment-resistant minimal change disease (TR-MCD).
Detailed description
Approximately 125 patients will be enrolled in this study across the United States. Patients with DN and FSGS/TR-MCD will be randomized in 3 ascending dose cohorts to receive either GFB-887 or placebo.
Interventions
DRUGGFB-887
Investigational Medicinal Product (IMP)
DRUGPlacebo
Matching
Sponsors
Goldfinch Bio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Multiple-ascending, placebo-controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* All patients: 1. Male or female 18-75 years of age, of any race, at the time of signing informed consent. 2. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 at Screening. 3. Currently receiving an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). * For DN patients: 1. Diagnosis of type 2 diabetes with glycated hemoglobin (HbA1c) level ≤11% at Screening. 2. UACR ≥ 150 mg/g. * For FSGS/TR-MCD patients: 1. Diagnosis of FSGS based on either biopsy or genetic testing or TR-MCD based on biopsy. 2. UPCR ≥ 1.0 g/g.
Exclusion criteria
* All patients: 1. Evidence of another (non-DN, non-FSGS/TR-MCD, respectively) kidney disease. 2. History of malignancy, unless in remission for at least 5 years other than adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, or prostate cancer not expected to require treatment over the course of the study. 3. History of any organ or bone marrow transplant, including kidney grafts. 4. History of alcoholism or drug/chemical abuse within 12 months prior to Screening. * For DN patients: 1. Renal disease that requires immunosuppressive therapy (currently, or in the past). 2. Body mass index (BMI) \>45 kg/m2. * For FSGS/TR-MCD patients: 1. Currently on calcineurin inhibitors or history of resistance to calcineurin inhibitors. 2. Body mass index (BMI) \>40 kg/m2. 3. Known history of severe or chronic hepatobiliary disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage change in Urine Protein-to-Creatinine Ratio (UPCR) | 12 weeks |
| Percentage change in Urine Albumin-to-Creatinine Ratio (UACR) | 12 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Percentage change in 24-hour urine protein excretion | 12 weeks |
| Percentage change in 24-hour urine albumin excretion | 12 weeks |
| Proportion of patients (DN or FSGS/TR-MCD) with a UACR/UPCR decrease of at least 30% of baseline | 12 weeks |
| Proportion of patients (DN or FSGS/TR-MCD) with a UACR/UPCR decrease of at least 40% of baseline | 12 weeks |
| Proportion of patients (DN or FSGS/TR-MCD) with a UACR/UPCR decrease of at least 50% of baseline | 12 weeks |
| Proportion of FSGS/TR-MCD patients achieving a modified partial remission | 12 weeks |
| Incidence of clinically significant changes in 12-lead electrocardiogram (ECG) parameters, vital signs measurements, and physical examinations | Approximately 12 weeks |
| Incidence of clinically significant changes in laboratory parameters | 12 weeks |
| Plasma pharmacokinetics (PK) parameters: maximum observed plasma concentration (Cmax) | 12 weeks |
| Plasma PK parameters: time of the observed plasma concentration (Tmax) | 12 weeks |
| Plasma PK parameters: area under the plasma concentration-time curve (AUC) | 12 weeks |
| Incidence and severity of adverse events | 12 weeks |
| Proportion of FSGS/TR-MCD patients achieving a complete remission | 12 weeks |
Countries
United States
Outcome results
None listed