Phase 2 Study: ManNAc for FSGS Shows Promise in Reducing Proteinuria

Status: RECRUITING | Phase: PHASE2 Condition(s): Focal Segmental Glomerulosclerosis Intervention(s): ManNAc (DRUG) Background: Focal segmental glomerulosclerosis (FSGS) is a disease that causes scarring in parts of the kidneys that filter waste. This can lead to protein loss in the urine, which can worsen kidney function. The kidneys may fail over time, and dialysis or a kidney transplant may be needed. Other treatments for this disease do not always work and often have adverse effects. Better treatments for FSGS are needed. Objective: To test a study drug (ManNAc) in people with FSGS. Eligibility: People aged 18 years and older with FSGS. Design: Participants will have 5 to 6 clinic visits over 14 weeks. Two of the visits will require overnight stays for 2 or 3 nights. ManNAc is a white powder that comes in a sachet. It is dissolved in water and taken twice a day by mouth. Participants will take their first dose at the clinic. They will learn how to store ManNAc and prepare each dose. They will record their doses in a diary. They will also write down any adverse effects or troubles they have using the drug at home. During clinic visits, participants will have physical exams with blood and urine tests. They will complete questionnaires about their health, sleep habits, and fatigue symptoms. During overnight visits, participants will also have 24-hour urine collection. A study team member will call participants 1 week after the first dose to check on their health. Follow-up phone calls will then be every 2 weeks after each clinic visit. Participants may meet with a dietitian to discuss nutrition while taking the ManNAc. Participants may choose to have genetic tests. Detailed: Study Description: Phase 2, open-label, single-arm, single-center study of ManNAc 2,000 mg oral (PO) twice daily (BID) for 12 weeks in 15 subjects with primary focal segmental glomerulosclerosis (FSGS). The study will characterize the long-term safety, tolerability, pharmacokinetics, and efficacy of ManNAc for proteinuria reduction in subjects with primary FSGS. We hypothesize that ManNAc will be safe and well-tolerated and will reduce proteinuria in subjects with primary FSGS. Objectives: Primary Efficacy Objective: Determine the efficacy of ManNAc therapy in reducing proteinuria in subjects with primary FSGS. Primary Safety Objective: Assess the long-term safety and tolerability of orally administered ManNAc to subjects with primary FSGS. Secondary Objectives: * Evaluate the long Primary Outcome(s): Determine the efficacy of ManNAc therapy in reducing proteinuria in subjects with primary FSGS.; Assess the long-term safety and tolerability of orally administered ManNAc to subjects with primary FSGS. Enrollment: 30 (ESTIMATED) Lead Sponsor: National Human Genome Research Institute (NHGRI) Start: 2026-04-01 | Primary Completion: 2027-11-30