Phase 1 Study of FG-3019 in Subjects With Type 1 or Type 2 Diabetes Mellitus and Diabetic Nephropathy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of two dosing regimens of FG-3019 administered over 12 weeks in patients with diabetic nephropathy and proteinuria on background angiotensin converting enzyme inhibitor (ACEi) and/or angiotensin II receptor antagonist (ARB) therapy.

Official Title
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A Randomized, Double-blind, Placebo-Controlled, Phase 1 Study of Safety, Pharmacokinetics and Pharmacodynamics of FG-3019 in Subjects With Type 1 or Type 2 Diabetes Mellitus and Diabetic Nephropathy on Background ACEi and/or ARB Therapy

Conditions
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Diabetes Mellitus, Diabetic Nephropathy

Intervention / Treatment
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* Drug: FG-3019
* Drug: FG-3019
* Drug: FG-3019


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years, inclusive Diagnosis of type 1 or type 2 diabetes according to American Diabetes Association (ADA) criteria First morning urinary ACR >0.200 g/g Receiving stable doses of ACEi and/or ARB therapy prior to Screening Estimated glomerular filtration rate of ≥20 and <90 mL/min/1.73 m2 Willingness to maintain ACEi and/or ARB therapy, and any additional anti-hypertensive therapies to control blood pressure, at a stable dose Maintenance of all additional antihypertensive medications, insulin, oral hypoglycemic agents, and cholesterol-lowering medications prior to randomization Exclusion Criteria: Female subjects who are pregnant or breastfeeding Organ transplant recipient, previous dialysis, or non-diabetic renal disease other than benign cysts or anatomical variants Any history of New York Heart Association (NYHA) class III/IV heart failure (HF) Screening electrocardiogram showing acute, clinically significant findings including but not limited to ST depression Recent history of serious heart problems (e.g. coronary artery bypass graft, cerebrovascular accident, or myocardial infarction) History of cancer in the past 5 years, possibly excluding non-melanomatous skin cancer, localized bladder cancer, or in situ cervical cancer. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies Participation in other studies of investigational drugs at the time of Screening AND receipt of an investigational drug within 42 days prior to Screening Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 times the upper limit of normal Hemoglobin <10 g/dL Positive for HIV (IgG) antibody

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: A<br>Placebo | Drug: FG-3019<br>* Placebo every 2 weeks IV for all infusions<br>|
| Experimental: B<br>FG-3019 5 mg/kg | Drug: FG-3019<br>* FG-3019 5 mg/kg every 2 weeks IV for all infusions<br>|
| Experimental: C<br>FG-3019 10 mg/kg | Drug: FG-3019<br>* FG-3019 10 mg/kg IV for infusions on Days 1, 15, 29 and 57 and Placebo IV on Days 43 and 71<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of FG-3019 |  | 34 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters |  | 34 weeks | 
| Change from baseline in first morning urinary albumin creatinine ratio (ACR) |  | 6 weeks (10 mg/kg) or 10 weeks (5 mg/kg) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 or Type 2 diabetes, proteinuria