A Study to Investigate the Efficacy and Safety of RG7774 in Patients With Diabetes Mellitus Type 1 or Type 2 With Treatment-Naive Diabetic Retinopathy

Study Overview
=================
Brief Summary
-----------------
The study's main purpose is to asses the safety, tolerability, and effect of oral administration of RG7774 on the severity of diabetic retinopathy (DR) in participants with moderately severe to severe non-proliferative diabetic retinopathy (NPDR) and good vision.

Official Title
-----------------
A Randomized, Double-Masked, 48-Week, Parallel-Group, Placebo-Controlled, Proof-of-Concept Study to Investigate the Efficacy and Safety of RG7774 in Patients With Diabetes Mellitus Type 1 or Type 2 With Treatment-Naive Diabetic Retinopathy

Conditions
-----------------
Diabetic Retinopathy

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: RG7774


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Able and willing to provide written informed consent and to comply with the study protocol according to International Conference of Harmonization (ICH) and local regulations Male and female patients of at least 18 years of age Treatment naïve with moderately severe to severe NPDR defined as ETDRS DRSS 47 or 53 Patients are eligible with and without DME in either eye BCVA score at screening of at least 70 letters in study eyes without DME and at least 75 letters in case DME is present Clear ocular media and adequate pupillary dilation to allow acquisition of good quality retinal images. Diagnosis of diabetes mellitus (DM) type 1 or type 2 Hemoglobin A1c (HbA1c) </= 12%. A female is eligible to participate if she is not pregnant, not breastfeeding Exclusion Criteria Ocular criteria for study eye: Prior treatment for DR or other retinal diseases with any approved or investigational therapy, including but not limited to intravitreal steroids, intravitreal anti-VEGF, light therapy, periocular pharmacological intervention, and laser (e.g. focal, grid, micropulse, or pan-retinal) Uncontrolled glaucoma Any concurrent intraocular condition (e.g. retinal detachment, dense cataract, epiretinal membrane with traction, or vitreomacular traction, etc.) that in the opinion of the Investigator could reduce the potential for improvement, require medical surgical intervention or may confound the visual and functional assessment and interpretation of study results Concurrent ocular conditions in either eye: Any active ocular infection Any active intraocular inflammation General Criteria: Previous systemic use of anti-VEGF drugs within 6 months prior to screening Complications of diabetes such as end-stage renal disease or liver disease Currently untreated diabetes mellitus or previously untreated patients who initiated oral or injectable anti-diabetic medication within 3 months prior to screening Uncontrolled blood pressure ([BP] defined as systolic > 180mmHg and/or diastolic >100 mmHg while patient at rest) History of concurrent cardio-vascular disease not considered well controlled by the Investigator Any major illness or major surgical procedure within one month before screening History of or currently active other diseases, metabolic dysfunction, physical examination finding, malignancies not considered cured, or clinical laboratory findings giving reasonable suspicion of a condition that contraindicated the use of the investigational medicinal drug or that might affect interpretation of the results of the study or renders the patient at high risk for treatment complications in the opinion of the investigator Known hypersensitivity to any of the excipients of the drug used, fluorescein dye or dilating eye drops Use of systemic medications known to be toxic to the lens, retina or optic nerve (e.g., deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines and ethambutol) used during the 6-month period prior to screening or likely need to be used

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group A<br>Participants will receive an oral dose of placebo matched to RG7774 once daily (QD) | Drug: Placebo<br>* Participants will receive oral placebo matched to RG7774<br>|
| Experimental: Group B<br>Participants will receive a low oral dose of RG7774 QD | Drug: RG7774<br>* Participants will receive oral RG7774<br>|
| Experimental: Group C<br>Participants will receive a high oral dose of RG7774 QD | Drug: RG7774<br>* Participants will receive oral RG7774<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants with >/= 2-Step Improvement in the Early Treatment Diabetic Retinopathy Study (ETDRS) DR Severity Scale (DRSS) from Baseline at Week 36 Measured in the Study Eye |  | Week 36 | 
| Percentage of Participants with Adverse Events (AEs) |  | From baseline up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Anterior Segment Neovascularization (ASNV), new Proliferative Diabetic Retinopathy (PDR), new Diabetic Macular Edema (DME), and Pre-Existing DME Requiring Intervention |  | From baseline up to 52 weeks | 
| Change from Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye |  | Baseline; Week 36 |