Clinical trial NCT05237388: Janus Kinase-STAT Inhibition to Reduce APOL1 Associated Kidney Disease
Official title: Janus Kinase-STAT Inhibition to Reduce APOL1 Associated Kidney Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Kidney Diseases
Keywords: APOL1
focal segmental glomerulosclerosis (FSGS)
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institute on Minority Health and Health Disparities (NIMHD)
name: Eli Lilly and Company
First posted: 2022-02-14
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Percent change in albuminuria (UACR)
timeFrame: Baseline, monthly for 6 months
Secondary outcomes:
measure: Percent change in eGFR as measured by blood test
timeFrame: Baseline, monthly for 6 months
measure: Percent change in urine CXCL 9-11 as measured by urine test
timeFrame: Baseline, monthly for 6 months
measure: Number of adverse events as measured by patient report
timeFrame: Up to 6 months
measure: Number of adverse events as measured by clinical lab value of hemoglobin less than 9.5g/dL
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Research at Pickett Road
state: North Carolina
Study officials:
affiliation: Duke University
name: Opeyemi Olabisi, MD
role: PRINCIPAL_INVESTIGATOR
References: