An Open-Label Phase 2 Study of N-Acetyl-D-Mannosamine (ManNAc) in Subjects With Primary Focal Segmental Glomerulosclerosis

* INCLUSION CRITERIA: Individuals must meet all the following inclusion criteria to be eligible to participate in this study: * Prior kidney biopsy demonstrating FSGS obtained within 10 years prior to the screening visit. * Age \>=18 years weighing more than 50 kg. * If the patient is on immunosuppressive therapy (e.g., prednisone, cyclosporine, tacrolimus or mycophenolate mofetil) he/she should be on these medications for at least 3 months prior to study evaluation and should be on a stable dose of the medication for at least 4 weeks before start of trial, with no plans to alter the regimen during 12 weeks of study period, except to stabilize levels and/or for any safety concerns. * Subjects will be allowed to continue with standard of care (SOC) non-immunosuppressant antiproteinuric agents to include RAAS inhibitors, mineralocorticoid antagonists (MRA), sodium-glucose co-transporter-2 inhibitors (SGLT2i), non-dihydropyridine calcium channel blockers (NDHP-CCBs), and glucagon-like peptide-1 (GLP-1) receptor agonists, in addition to other SOC adjuvant therapies such as diuretics, if they are able to maintain a stable dose throughout the trial. Subjects and their primary nephrologists will be encouraged to optimize their SOC treatments as much as possible prior to trial commencement. Subjects must be on a stable dose for at least 4 weeks before start of trial. Subjects should attempt to keep stable doses of both immunosuppressants and anti-proteinuric drugs throughout trial duration, to avoid confounding effects. Patients not receiving any of these SOC agents either due to allergy or intolerance will still be eligible. * Subjects must have a spot random urine PCR of \>= 2g/g on each of 3 measurements collected on at least 2 separate days during screening period plus a 24-hr urine protein collection of \>= 2g/day. The rationale for using this degree of proteinuria is that proteinuria beyond this threshold value significantly increases the risk of progressive decline of renal functions in the absence of effective therapies to mitigate this risk. Conversely, this threshold value could also allow for the selection of a cohort of patients who are most likely to benefit from ManNAc therapy. * Subjects with an estimated glomerular filtration rate (eGFR) \>=45 mL/min/1.73/m\^2 using the race-free CKD-EPI 2021 equation based on creatinine and cystatin-C \[Inker et al, 2021\]. The rationale is that below this eGFR threshold, sialic acid, the key metabolite of ManNAc markedly accumulates and may potentially result in systemic toxicity. Prior pharmacokinetic studies have shown that renal elimination of sialic acid is primarily through glomerular filtration, and it is neither reabsorbed nor secreted in the renal tubules. Hence decline in eGFR below 45 mL/min/1.73m\^2 directly correlates with rising blood sialic acid levels \[Fuentes et al, 2020\], in addition, these subjects may not benefit as much from ManNAc therapy as they have advanced disease pathology, which may be irreversible. Future studies with personalized precision ManNAc dosing may benefit the patient population with eGFR \<45 mL/min/1.73m\^2. * Subjects of reproductive potential must be willing to use at least one effective form of birth control throughout the trial period, unless they have had a permanent birth control procedure/intervention including but not limited to hysterectomy, tubal ligation and/or vasectomy. These may include the following: barrier methods (such as condoms), oral or depot injection (for example, Norplant or Depo-Provera) contraception medication, and/or intrauterine devices. * Evidence of a personally signed and dated informed consent indicating that the patient has been informed of all pertinent aspects of the study and their willingness to comply with all aspects of the study and their willingness to comply with all aspects of the study protocol, including treatment plan, laboratory tests, baseline and follow-up visits and procedures that include completion of daily diaries to record symptoms and medication intake. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: * Individuals who are unwilling or unable to provide informed consent. * Individual presenting for initial therapy of uncontrolled nephrotic syndrome which we define as proteinuria as measured by spot urine protein:creatinine ratio \>3g/g or 24-hour urine protein excretion of \>3.5g/day with symptomatic peripheral edema or pulmonary edema, hypoalbuminemia (serum albumin \<3.0g/dl), electrolyte disturbances (related or unrelated to medical therapy), and/or active thromboembolism (initiated on systemic anticoagulation in the last 3 months). The rationale for this criterion is that patient presenting for initial therapy for uncontrolled nephrotic syndrome may need to be initiated on various medications including immunosuppressives as well as non-immunosuppressive drugs which can significantly change the level of proteinuria. Additionally, fluid shifts due to diuretic use for treating edema can alter GFR which could confound the pharmacokinetics and pharmacodymanics of the investigational drug. * Individuals who acutely require optimization of volume status with intravenous diuretics to control volume overload, as this may result in fluid shifts between the intravascular space and the remainder of extracellular fluid volume. This might alter drug pharmacokinetics and pharmacodynamics as mentioned above in # 2. * Individuals with a psychiatric illness or neurological disease that in the judgement of the investigators would interfere with the ability to adhere with the requirements of this protocol. This includes, but is not limited to, uncontrolled/untreated psychotic depression, bipolar disorder, schizophrenia, substance abuse or dependence, antisocial personality disorder, panic disorder, or behavioral problems, which might interfere with effective communication. * Vulnerable individuals, including those with impaired cognitive function or are incarcerated. * Individuals whose renal biopsy shows evidence of an additional pathology along with FSGS. * Renal biopsy showing interstitial fibrosis and tubular atrophy (IFTA) \>50% per biopsy report. * Individuals with uncontrolled hypertension with blood pressures consistently \>140/90 mmHg on 3 or more community clinic blood pressure measurements. * Individuals with clinical evidence of any type of active infection including but not limited to HIV, Hepatitis B and/or Hepatitis C or patients who are positive on screening test for HIV including antibody or viral load, HBV surface antigen and/or HCV antibody. If a patient is positive for HCV antibody, then an HCV viral load will be measured to identify subjects with active infection. Additional tests may include those to screen for active CMV, Infectious Mononucleosis (Epstein-Barr Virus), parvovirus B19 and/or COVID-19 infection as per investigator judgement. * Individuals with evidence and/or documented history of progressive deterioration of liver functions, including the production of clotting factors, removal of toxic metabolic products, bile excretion for at least 6 months, routine hepatic laboratory indices including but not limited to (AST, ALT, or GGT) greater than 3 times the upper limit of normal, and/or individuals with a documented history and/or diagnosis of chronic liver disease. * Individuals with hypertriglyceridemia \>500 mg/dL. * Individuals with a documented history of malignancy (identified in last 5 years or on active therapy at time of screening). * Individuals with a documented history of Type I or Type II Diabetes Mellitus * Individuals with documented history of hematological conditions commonly associated with FSGS such as sickle cell disease and myeloproliferative disorders. * Individuals with a documented history of cardiac conditions commonly associated with FSGS such as congenital cyanotic heart disease. Individuals with a documented history of connective tissue disorders commonly associated with FSGS such as SLE and multiple sclerosis. * Individuals taking medications (either currently or within the last 6 months) associated with FSGS such as interferons, lithium, androgenic steroids, sirolimus, heroin, anthracyclines and bisphosphonates. * Individuals who are pregnant, will be breastfeeding or refuse birth control anytime during the study. * Individuals who have received treatment with another investigational drug, investigational device, or approved therapy for investigational use less than 60 days prior to planned ManNAc dosing. * Individuals with hypersensitivity to ManNAc. * Individuals who have been treated with ManNAc, sialic acid, IVIG, and/or other supplements containing sialic acid (e.g., sialyllactose) less than 60 days prior to planned ManNAc dosing. * Individuals who received a renal or any other solid organ and/or bone marrow/stem cell transplantation. * Individuals who in the judgment of the investigator, have a condition that places the subject at increased risk for AEs or has any other illness or clinical condition that might confound the results of the study or pose an additional risk in administering study drug to the subject. * Patients who need systemic immunosuppressive or glucocorticoid therapy for non-renal indication at any time throughout the trial. * Any patient receiving rituximab, cyclosphosphamide and/or plasmapheresis within 6 months of screening. * A documented history of active alcohol and/or substance abuse within the past 2 years. * Any patient with collapsing FSGS variant on renal biopsy. * Individuals with clinical history suggesting a post-adaptive FSGS such as those with neonatal history of low birth weight, congenital anomaly of the kidney or urinary tract (CAKUT) based on renal ultrasound findings or history of nephrectomy, vesicoureteral reflux or obesity as defined by Body Mass Index (BMI) \> 40kg/m\^2.