A Study of RG-012 in Subjects With Alport Syndrome

Study Overview
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Brief Summary
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This is a Phase 1, open-label, multi-center study of the safety, pharmacodynamics, and pharmacokinetics of RG-012 administered to subjects with Alport syndrome.

Detailed Description
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This is a Phase 1, multi-center study of the safety, pharmacodynamics, and pharmacokinetics of RG-012 administered to subjects with Alport syndrome. During this open-label study, all eligible subjects will receive RG-012. The study consists of two parts (Part A and Part B). During Part A, half of the participants will receive a single dose of RG-012 and half will receive 4 doses of RG-012 (one dose every other week for 6 weeks). All subjects will undergo two renal biopsies, one before and one after receiving RG-012, to assess the effect of RG-012 on the kidney. After completing Part A, subjects will be able to enter Part B of the study. During Part B, all subjects will receive RG-012 every other week for 48 weeks.

Official Title
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A Phase 1, Open-Label Study to Evaluate the Safety, Pharmacodynamics, and Pharmacokinetics of RG-012 for Injection, Including Its Effect on Renal microRNA-21, in Subjects With Alport Syndrome

Conditions
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Alport Syndrome

Intervention / Treatment
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* Drug: RG012


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females, ages 18 to 65 years Confirmed diagnosis of Alport syndrome eGFR between 40 and 90 mL/min/1.73m2 Proteinuria of at least 300 mg protein/g creatinine For subjects taking an ACE inhibitor or an ARB, the dosing regimen should be stable for at least 30 days prior to screening Willing to comply with contraception requirements Exclusion Criteria: Causes of chronic kidney disease aside from Alport syndrome (such as diabetic nephropathy, hypertensive nephropathy, lupus nephritis, or IgA nephropathy) End stage renal disease (ESRD) as evidenced by ongoing dialysis therapy or history of renal transportation Any other condition that may pose a risk to the subject's safety and well-being Female subjects who are pregnant or lactating

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RG-012 Single Dose<br>1.5 mg/kg RG012 subcutaneous injection | Drug: RG012<br>* RG012 in 0.3% sodium chloride<br>|
| Experimental: RG012 Every Other Week<br>1.5 mg/kg RG012 subcutaneous injections every other week | Drug: RG012<br>* RG012 in 0.3% sodium chloride<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety - Adverse Events | Incidence and severity of adverse events | 8 weeks | 
| Effect of RG-012 on renal microRNA-21 (miR-21) | Change in miR-21 expression in renal tissue | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) parameter - Cmax | Maximum observed plasma concentration | 8 weeks | 
| Pharmacokinetic (PK) parameter - Tmax | Time to maximum observed plasma concentration | 8 weeks | 
| Pharmacokinetic (PK) parameter - AUC | Area under the plasma concentration vs. time curve | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney disease, Nephritis, Hereditary kidney disease, Hereditary nephritis