Diabetic Retinopathy
Conditions
Keywords
Non-proliferative Diabetic Retinopathy
Brief summary
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.
Interventions
Oral dose of runcaciguat
OTHERPlacebo
Oral dose of matching placebo
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double-masked study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Improvement in DRSS by ≥ 2 Steps at 48 Weeks of Treatment in the Study Eye | At 48 weeks of treatment | DRSS (Diabetic Retinopathy Severity Scale) is measured on a 13-point scale and was graded centrally for the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Participants With Vision Threatening Complications (VTC) at 48 Weeks of Treatment in the Study Eye | At 48 weeks | VTC are defined as occurrence of any of the following AEs: * Proliferative diabetic retinopathy (PDR) (DRSS ≥61) * Any ocular neo-vascularization (retinal or anterior-segment neovascularization) * Center-involved (central Early Treatment Diabetic Retinopathy Study \[ETDRS\] subfield) DME * Drop of Best corrected visual acuity (BCVA) of 10 letters or more from baseline |
| Percentage of Participants With ≥ 2 Steps Improvement in DRSS at 24 Weeks of Treatment in the Study Eye | At 24 weeks of treatment | DRSS (Diabetic Retinopathy Severity Scale) is measured on a 13-point scale and was graded centrally for the study. |
| Percentage of Participants With ≥ 3 Steps Improvement in DRSS at 48 Weeks of Treatment on the for Persons Scale | At 48 weeks of treatment | DRSS (Diabetic Retinopathy Severity Scale) is measured on a 13-point scale and was graded centrally for the study. |
| Number of Participants With Treatment Emergent Adverse Event (TEAE) | From first dosing up to 28 days after last dose of study intervention | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With < 3 Steps Deterioration in DRSS at 48 Weeks of Treatment on the for Persons Scale | At 48 weeks of treatment | DRSS (Diabetic Retinopathy Severity Scale) is measured on a 13-point scale and was graded centrally for the study. |
Countries
Bulgaria, Czechia, Denmark, Germany, Latvia, Netherlands, Poland, Portugal, Romania, Slovakia, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 39 study centers in Europe and US that randomized 109 participants from 17 MAR 2021 (first patient first visit) to 22 APR 2024 (last patient last visit).
Pre-assignment details
Out of the 224 screened participants, 109 participants were randomized and started treatment. 115 participants did not pass screening. The primary reason for screen failure was that one or more inclusion or exclusion criteria were not met by the participant.
Participants by arm
| Arm | Count |
|---|---|
| Runcacigat (BAY1101042) Participants received runcaciguat gastrointestinal therapeutic system (GITS) tablets and were treated following an intra-individual dose-titration design with three titration steps. | 56 |
| Placebo Participants received matching placebo GITS tablets. | 53 |
| Total | 109 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 4 |
| Overall Study | Death | 2 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Non-compliance | 0 | 1 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
| Overall Study | Withdrawal cirterion met | 2 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | Runcacigat (BAY1101042) |
|---|---|---|---|
| Age, Continuous | 57.9 Years STANDARD_DEVIATION 11.5 | 57.1 Years STANDARD_DEVIATION 12.1 | 56.4 Years STANDARD_DEVIATION 12.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 50 Participants | 104 Participants | 54 Participants |
| Sex: Female, Male Female | 22 Participants | 47 Participants | 25 Participants |
| Sex: Female, Male Male | 31 Participants | 62 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 56 | 0 / 53 |
| other Total, other adverse events | 50 / 56 | 32 / 53 |
| serious Total, serious adverse events | 9 / 56 | 3 / 53 |
Outcome results
Primary
Percentage of Participants With Improvement in DRSS by ≥ 2 Steps at 48 Weeks of Treatment in the Study Eye
DRSS (Diabetic Retinopathy Severity Scale) is measured on a 13-point scale and was graded centrally for the study.
Time frame: At 48 weeks of treatment
Population: per protocol set: all full analysis set (FAS) participants of the respective study part without validity findings.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Runcacigat (BAY1101042) | Percentage of Participants With Improvement in DRSS by ≥ 2 Steps at 48 Weeks of Treatment in the Study Eye | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Improvement in DRSS by ≥ 2 Steps at 48 Weeks of Treatment in the Study Eye | 1.9 percentage of participants |
95% CI: [-0.08, 0.029]
Secondary
Number of Participants With Treatment Emergent Adverse Event (TEAE)
Time frame: From first dosing up to 28 days after last dose of study intervention
Population: Safety analysis set (SAF): All participants of the respective study part who took at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Runcacigat (BAY1101042) | Number of Participants With Treatment Emergent Adverse Event (TEAE) | 53 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Event (TEAE) | 44 Participants |
Secondary
Percentage of Participants With ≥ 2 Steps Improvement in DRSS at 24 Weeks of Treatment in the Study Eye
DRSS (Diabetic Retinopathy Severity Scale) is measured on a 13-point scale and was graded centrally for the study.
Time frame: At 24 weeks of treatment
Population: per protocol set: all full analysis set (FAS) participants of the respective study part without validity findings.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Runcacigat (BAY1101042) | Percentage of Participants With ≥ 2 Steps Improvement in DRSS at 24 Weeks of Treatment in the Study Eye | 0.0 percentage of participants |
| Placebo | Percentage of Participants With ≥ 2 Steps Improvement in DRSS at 24 Weeks of Treatment in the Study Eye | 0.0 percentage of participants |
Secondary
Percentage of Participants With ≥ 3 Steps Improvement in DRSS at 48 Weeks of Treatment on the for Persons Scale
DRSS (Diabetic Retinopathy Severity Scale) is measured on a 13-point scale and was graded centrally for the study.
Time frame: At 48 weeks of treatment
Population: per protocol set: all full analysis set (FAS) participants of the respective study part without validity findings.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Runcacigat (BAY1101042) | Percentage of Participants With ≥ 3 Steps Improvement in DRSS at 48 Weeks of Treatment on the for Persons Scale | 0.0 percentage of participants |
| Placebo | Percentage of Participants With ≥ 3 Steps Improvement in DRSS at 48 Weeks of Treatment on the for Persons Scale | 1.9 percentage of participants |
Secondary
Percentage Participants With Vision Threatening Complications (VTC) at 48 Weeks of Treatment in the Study Eye
VTC are defined as occurrence of any of the following AEs: * Proliferative diabetic retinopathy (PDR) (DRSS ≥61) * Any ocular neo-vascularization (retinal or anterior-segment neovascularization) * Center-involved (central Early Treatment Diabetic Retinopathy Study \[ETDRS\] subfield) DME * Drop of Best corrected visual acuity (BCVA) of 10 letters or more from baseline
Time frame: At 48 weeks
Population: per protocol set: all full analysis set (FAS) participants of the respective study part without validity findings.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Runcacigat (BAY1101042) | Percentage Participants With Vision Threatening Complications (VTC) at 48 Weeks of Treatment in the Study Eye | 17.6 percentage of participants |
| Placebo | Percentage Participants With Vision Threatening Complications (VTC) at 48 Weeks of Treatment in the Study Eye | 11.5 percentage of participants |
Other Pre-specified
Percentage of Participants With < 3 Steps Deterioration in DRSS at 48 Weeks of Treatment on the for Persons Scale
DRSS (Diabetic Retinopathy Severity Scale) is measured on a 13-point scale and was graded centrally for the study.
Time frame: At 48 weeks of treatment
Population: per protocol set: all full analysis set (FAS) participants of the respective study part without validity findings.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Runcacigat (BAY1101042) | Percentage of Participants With < 3 Steps Deterioration in DRSS at 48 Weeks of Treatment on the for Persons Scale | 78.4 percentage of participants |
| Placebo | Percentage of Participants With < 3 Steps Deterioration in DRSS at 48 Weeks of Treatment on the for Persons Scale | 80.8 percentage of participants |