Janus Kinase-STAT Inhibition to Reduce APOL1 Associated Kidney Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if the drug, baricitinib, is safe and effective in reducing high levels of albumin in the urine (albuminuria) in African American/Blacks with APOL1- associated focal segmental glomerulosclerosis (FSGS) and non-diabetic APOL1-associated chronic kidney disease due to hypertension (HTN-CKD).

Official Title
-----------------
Janus Kinase-STAT Inhibition to Reduce APOL1 Associated Kidney Disease

Conditions
-----------------
Chronic Kidney Diseases

Intervention / Treatment
-----------------
* Drug: Baricitinib
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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 after treatment). Previous kidney transplant. 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. 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 an unstable dosing regimen of corticosteroids within 2 weeks of study entry or within 6 weeks of planned randomization.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Baricitinib<br>Participants will take one pill of Baricitinib daily with their regular medications. | Drug: Baricitinib<br>* One pill daily<br>|
| Placebo Comparator: Placebo<br>Participants will take a Baricitinib placebo pill matching Baricitinib daily with their regular medications. | Drug: Placebo<br>* Baricitinib placebo pill<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in albuminuria (UACR) |  | Baseline, monthly for 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in eGFR as measured by blood test |  | Baseline, monthly for 6 months | 
| Percent change in urine CXCL 9-11 as measured by urine test |  | Baseline, monthly for 6 months | 
| Number of adverse events as measured by patient report |  | Up to 6 months | 
| Number of adverse events as measured by clinical lab value of hemoglobin less than 9.5g/dL |  | Up to 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
APOL1, focal segmental glomerulosclerosis (FSGS)