Non-proliferative Diabetic Retinopathy Treated With Runcaciguat

Study Overview
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Brief Summary
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This Phase 2 study is conducted to investigate the safety and efficacy of runcaciguat in the treatment of diabetic retinopathy. To assess efficacy, the retinal morphology will be investigated by 7-field color fundus photography for central assessment of the diabetic retinopathy severity score, or DRSS. Two-step DRSS improvement at 24 weeks of treatment will be the primary efficacy endpoint. DRSS assessments are repeated after completion of 48 weeks of treatment. In addition, vision threatening complications will be recorded throughout the study and assessed as secondary efficacy endpoint.

Official Title
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A Phase 2 Randomized, Placebo-controlled, Double-masked Proof-of-concept Study to Investigate the Efficacy and Safety of Runcaciguat (BAY 1101042) in Patients With Moderately Severe to Severe Non-proliferative Diabetic Retinopathy

Conditions
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Diabetic Retinopathy

Intervention / Treatment
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* Drug: Runcaciguat (BAY1101042)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Moderately severe to severe NPDR in the study eye: Diabetic Retinopathy Severity Scale (DRSS) levels 47 or 53 Diabetes type 1 or 2 Best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score in the study eye of ≥69 letters (approximate Snellen equivalent of 20/40 or better) Main Exclusion Criteria: Presence or history of macular edema involving the center of the macula Any kind of neovascular growth in the study eye, including anterior segment neovascularization Arterial hypotension with systolic blood pressure < 100 or diastolic blood pressure < 60mmHg Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) above 3 x Upper limit of normal (ULN) or bilirubin ≥ 1.5 ULN at screening, known ascites Estimated glomerular filtration rate (eGFR CKD-EPI) below 30 ml/min/1.73 m^2 at screening Any prior systemic anti-Vascular endothelial growth factor (VEGF) treatment or IVT anti-VEGF treatment in the study eye Any prior intraocular steroid injection in the study eye Any prior grid or focal laser photocoagulation within 500 microns of the foveal center or any prior Pan-retinal photocoagulation (PRP) in the study eye Use of nitrates or Nitric oxide (NO) donors (such as amyl nitrate) in any form including topical; Phosphodiesterase 5 (PDE5) inhibitors, nonspecific PDE inhibitors within 1 week or less than 5 half-lives (whichever is longer) before first study drug administration

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Runcaciguat (BAY1101042)<br> | Drug: Runcaciguat (BAY1101042)<br>* Oral dose of runcaciguat<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Oral dose of matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DRSS improvement ≥2 steps at 48 weeks of treatment in the study eye | DRSS (Diabetic Retinopathy Severity Scale) will be graded centrally. | At 48 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vision threatening complications at 48 weeks of treatment in the study eye |  | At 48 weeks | 
| DRSS improvement ≥2 steps at 24 weeks of treatment in the study eye | DRSS (Diabetic Retinopathy Severity Scale) will be graded centrally. | At 24 weeks | 
| Frequency of treatment emergent adverse events | As reported by Investigators | From first dosing up to 28 days after last dose of study intervention. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-proliferative Diabetic Retinopathy