Janus Kinase-STAT Inhibition to Reduce APOL1 Associated Kidney Disease

Prior treatment

• Symptomatic herpes zoster infection within 12 weeks prior to study entry.
• Previous kidney transplant.
• Prior or current treatment with JAK inhibitor.
• High dose corticosteroids (\>10 mg per day of prednisone or equivalent) or an unstable dosing regimen of corticosteroids within 2 weeks of study entry or within 6 weeks of planned randomization.

Other illness

• Diabetes
• HIV
• Sickle cell disease.
• Active serious viral, bacterial, fungal or parasitic infection.
• Positive hepatitis B surface antigen during screening (could enroll after treatment).

Lab values

• History of chronic liver disease with the most recent available aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>1.5 times the ULN or the most 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.

Other

• Tip variant of FSGS.
• Systolic BP \>180 mmHg or diastolic BP \>90 mmHg based on average of 3 measurements.
• Pregnant or nursing at time of enrollment
• Current use of potent immunosuppressants such as abatacept, adalimumab, anakinra, azathioprine, certolizumab, etanercept, golimumab, infliximab, probenecid, rituximab, ruxolitinib, sarilumab, tofacitinib, or tocilizumab.

• 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