A Study in Participants With Diabetic Kidney Disease

Study Overview
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Brief Summary
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The purpose of this study is to determine if LY2382770 is safe and effective at protecting kidney function in participants with kidney disease due to diabetes.

Detailed Description
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The primary objective is to determine if LY2382770, administered monthly for 1 year, is more effective than placebo at slowing the progression of diabetic kidney disease in participants treated with an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB).

Official Title
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A Randomized, Double-Masked, Placebo-Controlled, Multicenter, Phase 2 Study to Evaluate the Safety and Renal Efficacy of LY2382770 in Patients With Diabetic Kidney Disease Due to Type 1 or Type 2 Diabetes

Conditions
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Diabetic Kidney Disease, Diabetic Nephropathy, Diabetic Glomerulosclerosis

Intervention / Treatment
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* Drug: LY2382770
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Participants with chronic kidney disease presumed due to diabetes Type 1 or Type 2 Participants with certain levels of kidney function - serum creatinine (SCr) 1.3 to 3.3 mg/dl (115 to 291 micromol/L) inclusive for women and 1.5 to 3.5 mg/dl (132 to 309 micromol/L) inclusive for men, or an estimated glomerular filtration rate (eGFR) 20 to 60 mL/min/1.73 m² Participants with protein in the urine - 24-hour urine protein/creatinine ratio (PCR) greater than or equal to 800 mg/g (greater than or equal to 91 mg/mmol). Participants must be on a stable and acceptable dose of an ACE (angiotensin-converting enzyme) inhibitor or an ARB (angiotensin II receptor blocker), or not able to tolerate these medications. Main Exclusion Criteria: Female participants who can become pregnant, are pregnant or breastfeeding Participants who have any of the following medical conditions (the site research staff will discuss these criteria and determine a participant's ability to participate) Chronic inflammatory or autoimmune diseases Chronic Kidney Disease from causes other than diabetes An organ transplant Too high a blood pressure Viral Hepatitis B or C liver infection, liver cirrhosis, or significant liver disease Recent gastrointestinal bleeding Acute kidney injury within the 3 months before screening Major surgery within 3 months before screening or plan to have it during the study period HIV infection- the virus that causes AIDS Heart disease that is not considered stable Cancer that is too recent or other condition which poses too high a risk for developing cancer Required to take drugs that change the immune system

Ages Eligible for Study
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Minimum Age: 25 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Subcutaneous injection given monthly for 12 months<br>|
| Experimental: 2 mg LY2382770<br> | Drug: LY2382770<br>* Subcutaneous injection given monthly for 12 months<br>|
| Experimental: 10 mg LY2382770<br> | Drug: LY2382770<br>* Subcutaneous injection given monthly for 12 months<br>|
| Experimental: 50 mg LY2382770<br> | Drug: LY2382770<br>* Subcutaneous injection given monthly for 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Log Transformed (In) Serum Creatinine From Baseline to 12 Month Endpoint | Analysis of covariance (ANCOVA) model was used with treatment, visit, and treatment-by-visit interaction as fixed effects, subject as random effect, baseline Serum Creatinine log transformed (ln) and first morning urine protein to creatinine ratio (PCR) log transformed (ln) as covariates. | Baseline, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Log Transformed (ln) Urine Protein/Creatinine Ratio From Baseline to 12 Month Endpoint | Analysis of covariance (ANCOVA) model was used with treatment, visit, and treatment-by-visit interaction as fixed effects, subject as random effect, baseline Serum Creatinine log transformed (ln) and first morning urine protein to creatinine ratio (PCR) log transformed (ln) as covariates. | Baseline, 12 months | 
| Population Pharmacokinetics (PK) - Model-Estimated Area Under the Concentration -Time Curve (AUC ) Over a Dosing Interval |  | Baseline through 12 months (samples collected pre and/or postdose at monthly intervals) | 
| Log Transformed (ln) Serum Creatinine Slope of Change From Baseline Through 12 Months | Analysis of covariance (ANCOVA) model was used with treatment as fixed effects and baseline Serum Creatinine log transformed (ln) and first morning urine protein to creatinine ratio (PCR) log transformed (ln) as covariates. | Baseline through 12 months | 
| Estimated Glomerular Filtration Rate (eGFR) Slope of Change From Baseline Through 12 Months | Analysis of covariance (ANCOVA) model was used with treatment as fixed effects, baseline Serum Creatinine log transformed (ln) and first morning urine protein to creatinine ratio (PCR) ) log transformed (ln) as covariates. | Baseline through 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Kidney Disease, Diabetic Kidney Disease, End-Stage Renal Disease, Transforming Growth Factor beta 1 Monoclonal Antibody, Type 1 Diabetes, Type 2 Diabetes