Baricitinib for Chronic Kidney Disease

(JUSTICE Trial)

Overseen By Maurice Smith

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Duke University

Must be taking: Antihypertensives

Must not be taking: JAK inhibitors, Immunosuppressants, Corticosteroids

Disqualifiers: Diabetes, HIV, Sickle cell, others

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called baricitinib (also known as Olumiant) to determine its safety and effectiveness in reducing high levels of protein in the urine, often indicating kidney issues. It specifically targets African American or Black individuals with certain kidney conditions linked to a genetic factor called APOL1. Participants will take either baricitinib or a placebo (a pill with no active drug) alongside their regular medications. Suitable candidates have been diagnosed with kidney problems not caused by diabetes, such as high blood pressure-related kidney disease, and have stable blood pressure treatment. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants the opportunity to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial requires that you have been on a stable antihypertensive medication regimen for at least 1 month before joining. You cannot participate if you are currently using certain potent immunosuppressants or high-dose corticosteroids. The protocol does not specify other medication restrictions, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that baricitinib is likely to be safe for humans?

Research has shown that baricitinib is generally safe for most people and has been used to treat conditions like diabetic kidney disease. However, it is not recommended for individuals with severe kidney problems, such as those on dialysis or with very low kidney function. The drug may not exit the body quickly in these cases, potentially increasing its effects and side effects.

Most people taking baricitinib have not reported serious side effects, though some have experienced mild issues like nausea or headaches. Consulting a doctor is crucial for those with kidney concerns before considering baricitinib. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic kidney disease?

Unlike the standard treatments for chronic kidney disease, which often include blood pressure medications and blood sugar control, Baricitinib is unique because it targets the Janus kinase (JAK) pathway. This pathway plays a crucial role in inflammation and immune response, offering a novel way to address kidney damage that these traditional treatments may not fully tackle. Researchers are excited about Baricitinib as it could potentially reduce inflammation more effectively, possibly slowing down the progression of kidney disease in a way current options do not.

What evidence suggests that baricitinib might be an effective treatment for chronic kidney disease?

Research has shown that baricitinib, a medication that blocks certain proteins causing inflammation, may help with kidney problems. In people with diabetic kidney disease, baricitinib reduced the amount of albumin in urine, a sign of kidney issues. This trial will evaluate baricitinib's potential to address similar problems in chronic kidney disease from other causes, such as high blood pressure. Although baricitinib has mainly been studied in diabetes, its mechanism offers hope for broader applications. Additionally, baricitinib has proven effective in treating rheumatoid arthritis, even in individuals with some kidney issues, indicating its potential benefits for kidney health. Participants in this trial will receive either baricitinib or a placebo to assess its effectiveness in chronic kidney disease. ^{3 6 7 8 9}

Who Is on the Research Team?

Opeyemi Olabisi, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for African American/Black adults aged 18-70 with high-risk APOL1 genotype, diagnosed FSGS or HTN-CKD without diabetes, HIV, sickle cell disease, recent serious infections, previous kidney transplant, certain liver conditions or low blood counts. Participants must have stable blood pressure and not be on potent immunosuppressants.

Inclusion Criteria

My blood pressure medication has not changed in the last month.

I have been diagnosed with FSGS or have high blood pressure-related kidney disease.

Able to provide written informed consent

Exclusion Criteria

I am currently taking strong medications to suppress my immune system.

I have had a kidney transplant.

I have been treated with a JAK inhibitor before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Baricitinib or a placebo daily to assess the reduction of albuminuria

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Baricitinib

Trial Overview

The study tests if baricitinib can safely reduce albuminuria in patients with APOL1-associated kidney diseases compared to a placebo. It's focused on those who don't have diabetes but suffer from FSGS or chronic kidney disease due to hypertension.

How Is the Trial Designed?

Group I: Baricitinib Experimental Treatment 1 Intervention

Participants will take one pill of Baricitinib daily with their regular medications.

Group II: Placebo Placebo Group 1 Intervention

Participants will take a Baricitinib placebo pill matching Baricitinib daily with their regular medications.

Baricitinib is already approved in United States, European Union for the following indications:

Approved in United States as Olumiant for:

• Rheumatoid arthritis
• Severe alopecia areata
• COVID-19

Approved in European Union as Olumiant for:

• Rheumatoid arthritis
• Severe alopecia areata
• COVID-19

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

National Institute on Minority Health and Health Disparities (NIMHD)

Collaborator

Trials

473

Recruited

1,374,000+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

Baricitinib has shown real-world effectiveness in treating moderate-to-severe rheumatoid arthritis, with 8.7-60% of patients achieving remission within 12 weeks and 20.2-81.6% reaching low disease activity by 24 weeks, indicating its efficacy across various patient backgrounds.

The safety profile of baricitinib remains consistent with previous clinical studies, and it demonstrates high drug persistence rates comparable to anti-tumor necrosis factor drugs, suggesting it is a reliable treatment option for patients with rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Literature Review of Real-World Evidence on Baricitinib for the Treatment of Rheumatoid Arthritis. Hernández-Cruz, B., Kiltz, U., Avouac, J., et al.[2023]

In a study of 98 rheumatoid arthritis patients treated with Baricitinib or Tofacitinib over a period from September 2017 to January 2020, both medications significantly reduced disease activity scores without showing differences in effectiveness between the two treatments.

The safety profile for both drugs was comparable, with similar rates of adverse events, including infections, and no serious complications such as tuberculosis or cardiovascular events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world Effectiveness and Safety of JAK Inhibitors in Rheumatoid Arthritis: A Single-centre Study. González Mazarío, R., Fragío Gil, JJ., Ivorra Cortés, J., et al.[2022]

In a study using uninephrectomized BKS-Lepr-/- (db/db) mice, the addition of Bromoindirubin-3'-oxime (BIO) to standard treatments (metformin, ramipril, and empagliflozin) significantly improved kidney function and podocyte health, indicating its potential as a renoprotective agent in type 2 diabetes.

The combination of BIO with standard therapies showed additive benefits in reducing kidney damage markers, such as albuminuria and glomerulosclerosis, suggesting that using multiple drugs may help slow the progression of chronic kidney disease (CKD) in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Testing for Residual Progression of Diabetic Kidney Disease in Mice Beyond Therapy with Metformin, Ramipril, and Empagliflozin. Motrapu, M., Świderska, MK., Mesas, I., et al.[2021]

In a study of 36,951 individuals with chronic kidney disease (CKD) and type 2 diabetes (T2D), metformin was the most commonly prescribed glucose-lowering therapy, with patients spending a median of approximately 75% of their follow-up time on this medication.

As kidney function declined (measured by eGFR), there was a noticeable trend of reduced metformin prescriptions, indicating a need for better management strategies for CKD patients with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucose-lowering treatment pathways of individuals with chronic kidney disease and type 2 diabetes according to the Kidney Disease: Improving Global Outcomes 2012 risk classification. Pollock, C., Sanchez, JJG., Carrero, JJ., et al.[2023]

Dapagliflozin significantly reduced the risk of serious kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) across all levels of frailty, demonstrating its efficacy regardless of frailty status.

The safety profile of dapagliflozin was consistent across frailty categories, with a lower occurrence of serious adverse events compared to placebo, indicating it is a safe treatment option for frail patients with CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Dapagliflozin in Patients with Chronic Kidney Disease across the Spectrum of Frailty. Vart, P., Butt, JH., Jongs, N., et al.[2023]

Baricitinib demonstrated a consistent safety profile over 128 weeks in patients with rheumatoid arthritis, with treatment-emergent adverse events occurring in 63% of patients on 4 mg and 67% on 8 mg, and no unexpected late safety signals identified.

Clinical improvements in disease symptoms were maintained beyond the initial 24-week blinded period, with similar or increased rates of disease improvement observed at weeks 76 and 128, indicating the long-term efficacy of baricitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Baricitinib Through 128 Weeks in an Open-label, Longterm Extension Study in Patients with Rheumatoid Arthritis. Keystone, EC., Genovese, MC., Schlichting, DE., et al.[2021]

In a study of 1,450 type 2 diabetic patients with advanced chronic kidney disease (CKD), SGLT2 inhibitors significantly reduced the rates of kidney-related adverse events (7.7% vs. 24.1%) and major adverse cardiovascular events (MACE) (9.6% vs. 15.1%) compared to a control group.

Patients using SGLT2 inhibitors also showed improved kidney function (eGFR increased by 0.4 ml/min/1.73 m²) and better glycemic control (HbA1c decreased by -0.40%), with only a slight increase in urinary tract infections, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGLT2 inhibitors reduce adverse kidney and cardiovascular events in patients with advanced diabetic kidney disease: A population-based propensity score-matched cohort study. Chan, GC., Ng, JK., Chow, KM., et al.[2023]

In a Phase 2 study involving 129 adults with Type 2 diabetes at high risk for diabetic kidney disease, baricitinib (4 mg daily) significantly reduced morning urine albumin-creatinine ratio (UACR) by 41% after 24 weeks compared to placebo, indicating its efficacy in lowering albuminuria.

Baricitinib also decreased several inflammatory biomarkers over the study period, although it was associated with a higher rate of anemia (32%) compared to placebo (3.7%), highlighting a potential safety concern that needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK1/JAK2 inhibition by baricitinib in diabetic kidney disease: results from a Phase 2 randomized controlled clinical trial. Tuttle, KR., Brosius, FC., Adler, SG., et al.[2021]

In a study of 87 Japanese participants with type 2 diabetes and chronic kidney disease, SGLT2 inhibitors showed a significant improvement in renal function, particularly in those with normoalbuminuria (A1) and microalbuminuria (A2) after 2 years of treatment.

Participants with normoalbuminuria experienced a greater increase in estimated glomerular filtration rate (eGFR) compared to those with macroalbuminuria (A3), indicating that SGLT2 inhibitors may be more effective in preserving kidney function in patients with lower levels of albumin in their urine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of sodium-glucose cotransporter 2 inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease with normoalbuminuria. Nakamura, A., Miyoshi, H., Kameda, H., et al.[2022]

Baricitinib, a selective JAK1 and JAK2 inhibitor, was found to be safe and well tolerated in healthy volunteers, with no serious treatment-related adverse events reported during the studies.

The drug demonstrated predictable pharmacokinetics, achieving peak plasma concentration within 1.5 hours and showing a dose-linear response, which suggests it could be effective for treating rheumatoid arthritis and other inflammatory disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetics, pharmacodynamics, and safety of baricitinib, an oral JAK 1/2 inhibitor, in healthy volunteers. Shi, JG., Chen, X., Lee, F., et al.[2021]

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Baricitinib for Chronic Kidney Disease (JUSTICE Trial)

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Renal Impairment. There are limited data for baricitinib in patients with severe renal impairment: • Baricitinib is not recommended for patients who are on ...