Janus Kinase-STAT Inhibition to Reduce APOL1 Associated Kidney Disease

Inclusion Criteria:

• Adults 18-70 years

• High Risk APOL1 genotype (i.e., G1G1, G2G2, or G1G2)

• FSGS diagnosed by kidney biopsy or clinically diagnosed HTN-CKD

• UACR ≥300 mg/dL

• Estimated glomerular filtration rate (eGFR) ≥26 ml/min/1.73 m2 at screening

• Stable antihypertensive regimen for ≥ 1 month prior to enrolment

• Able to provide written informed consent

Exclusion Criteria:

• Diabetes

• HIV

• Sickle cell disease.

• Tip variant of FSGS.

• Systolic BP >180 mmHg or diastolic BP >90 mmHg based on average of 3 measurements.

• Active serious viral, bacterial, fungal or parasitic infection.

• Symptomatic herpes zoster infection within 12 weeks prior to study entry.

• Positive hepatitis B surface antigen during screening (could enroll aftertreatment).

• Previous kidney transplant.

• History of chronic liver disease with the most recent available aspartateaminotransferase (AST) or alanine aminotransferase (ALT) >1.5 times the ULN or themost recent available total bilirubin ≥1.5 times the ULN

• Hemoglobin <10 g/dL.

• Absolute lymphocyte count (ALC)<500cells/mm3 or absolute neutrophil count (ANC) < 1000 cells/mm3.

• Pregnant or nursing at time of enrollment

• Prior or current treatment with JAK inhibitor.

• Current use of potent immunosuppressants such as abatacept, adalimumab, anakinra,azathioprine, certolizumab, etanercept, golimumab, infliximab, probenecid,rituximab, ruxolitinib, sarilumab, tofacitinib, or tocilizumab.

• High dose corticosteroids (>10 mg per day of prednisone or equivalent) or anunstable dosing regimen of corticosteroids within 2 weeks of study entry or within 6weeks of planned randomization.