A Study to Test Safety and Efficacy of Baricitinib in Participants With Diabetic Kidney Disease

Study Overview
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Brief Summary
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This is a dose ranging study to evaluate the safety and efficacy of baricitinib in the treatment of participants with mild to moderate diabetic kidney disease.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Phase 2 Study to Evaluate the Safety and Renal Efficacy of Baricitinib in Patients With Diabetic Kidney Disease

Conditions
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Diabetic Kidney Disease

Intervention / Treatment
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* Drug: Baricitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with Type 2 diabetes treated with at least one antihyperglycemic medicine for 12 months Have diabetic kidney disease and receiving one of two specific medicines used to treat high blood pressure or diabetic kidney disease for at least 3 months Estimated Glomerular Filtration Rate (eGFR) of 25 to 70 milliliter per minute per 1.73 square meter (mL/min/1.73 m²) (as determined by the Chronic Kidney Disease Epidemiology Collaboration equation) and a urinary albumin/creatinine ratio (UACR) >300 milligram per gram (mg/g) and <5000 mg/g Exclusion Criteria: Too high blood pressure when you enter the study Some specific medicines used to treat high blood pressure or diabetic kidney disease Frequent high blood glucose levels Renal transplant or past history of dialysis Nonsteroidal anti-inflammatory drugs (NSAIDs) Had a special X-ray in the past 30 days which involved also receiving an injection of dye into the vein Major surgery within 8 weeks of study entry or will require major surgery during the study Some types of vaccination Shingles or currently have symptoms of a cold sore Serious viral, bacterial, fungal, or parasitic infection, or a urinary infection, Tuberculosis (TB) Human immunodeficiency virus (HIV) infection- the virus that causes Acquired immunodeficiency syndrome (AIDS) Have or had some blood disorders, enlarged lymph glands or spleen, or some cancers. Serious circulatory, breathing, liver, stomach or bowel problems, neurological or psychiatric disorders Heart attack or heart failure, or a stroke Other serious disorders or illnesses Electrocardiogram (ECG) heart trace abnormalities Alcohol or illegal drug abuse Donated more than 500 mL of blood in the last 30 days (no blood donations allowed during the study) Pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Administered orally, given as three placebo tablets in the morning and one placebo tablet in the evening for 24 weeks. | Drug: Placebo<br>* Administered orally<br>|
| Experimental: Baricitinib 0.75 mg/0.5 mg QD<br>Administered orally, 0.75 mg given as one 0.75 mg tablets and two placebo tablets in the morning and one placebo tablet in the evening for 24 weeks or 0.5 mg given as one 0.5 mg tablet and two placebo tablets in the morning and one placebo tablet in the evening for 24 weeks. Placebo tablets given to maintain blind. | Drug: Baricitinib<br>* Administered orally<br>* Other names: INCB28050;Drug: Placebo<br>* Administered orally<br>|
| Experimental: Baricitinib 0.75 mg/0.5 mg BID<br>Administered orally, 0.75 mg given as one 0.75 tablet and 2 placebo in the morning and one 0.75 mg tablet in the evening for 24 weeks or 0.5 mg given as one 0.5 mg tablet and two placebo tablets in the morning and one 0.5 mg tablet in the evening. Placebo tablets given to maintain blind. | Drug: Baricitinib<br>* Administered orally<br>* Other names: INCB28050;Drug: Placebo<br>* Administered orally<br>|
| Experimental: Baricitinib 1.5 mg/1 mg<br>Administered orally, 1.5 mg given as two 0.75 mg tablets and 1 placebo tablet in the morning and one placebo tablet in the evening for 24 weeks or 1 mg tablet and two placebo tablets in the morning and one placebo tablet in the evening for 24 weeks. Placebo tablets given to maintain blind. | Drug: Baricitinib<br>* Administered orally<br>* Other names: INCB28050;Drug: Placebo<br>* Administered orally<br>|
| Experimental: Baricitinib 4 mg/2.75 mg<br>Administered orally, 4 mg given as one tablet and 2 placebo tablets in the morning and one placebo tablet in the evening for 24 weeks or 2.75 mg given as two 1 mg tablets and one 0.75 mg tablet in the morning and one placebo tablet in the evening for 24 weeks. Placebo tablets given to maintain blind. | Drug: Baricitinib<br>* Administered orally<br>* Other names: INCB28050;Drug: Placebo<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Urinary Albumin/Creatinine Ratio (UACR) at Week 24 | UACR is a potential marker of chronic kidney disease, calculated as a ratio of Urinary Albumin and Urinary Creatinine. The least squares mean (LS mean) are from mixed model repeated measures (MMRM) analyses which include treatment, baseline estimated Glomerular Filtration Rate (eGFR) group (higher: 50 to 70 mL/min/1.73m² and lower: 25 to <50 mL/min/1.73m²), visit, treatment-by-visit interaction, baseline UACR, and baseline UACR-by-visit interaction. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Urinary Monocyte Chemotactic Protein 1 (MCP-1)/Creatinine Ratio |  | Baseline, Week 24 | 
| Change From Baseline in Creatinine Clearance at Week 24 | Creatinine clearance is the amount of creatinine cleared from kidney within 24 hours. The LS mean was from MMRM analyses which included treatment, baseline eGRF group, visit, treatment-by-visit interaction, baseline Creatinine Clearance, and baseline Creatinine Clearance-by-visit interaction. | Baseline, Week 24 | 
| Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Week 24 | EQ-5D-5L is a 2-part measurement. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1. A higher score indicates better health state. The second part is assessed using a visual analog scale (VAS) that ranged from 0 to 100mm, where 0 is the worst health you can imagine and 100 is the best health you can imagine. The LS means are analyzed using an analysis of covariance (ANCOVA) model with treatment, baseline eGFR group, and baseline VAS score or baseline health state index score as covariates. | Baseline, Week 24 | 
| Pharmacokinetics (PK): Area Under the Concentration-Time Curve at Steady State (AUC,ss) | Evaluable pharmacokinetic concentrations from the 2-week, 4-week, 8-week, 12-week, 16-week, 20-week and 24-week time points were combined and utilized in a population approach to determine the population mean estimate and standard deviation at steady-state. | Weeks 2 and 4 (1-2 hours postdose), 8 (3-6 hours postdose), 12 (in fasted state), 16 and 20 (6-9 hours postdose), 24 (in fasted state) |