Diabetic Macular Edema
Conditions
Keywords
Diabetic Macular Edema, Diabetic Retinopathy, Diabetes, Retinal, Macular Thickening, Plasma Kallikrein Inhibitor
Brief summary
The objective of this trial is to assess the safety, efficacy, and tolerability of RZ402 in patients with Diabetic Macular Edema.
Detailed description
Diabetic macular edema (DME) is a common retinal microvascular complication in diabetic patients that can lead to progressive loss of visual acuity and ultimately to complete vision loss. DME is the main cause of vision loss in patients with Type 2 diabetes. There is a significant unmet medical need to develop better therapies of DME and diabetic retinopathy (DR). RZ402 is a potent and selective plasma kallikrein inhibitor (PKI), which is being developed as an oral therapy for the chronic treatment of DME and DR. This is a Phase 2, Randomized, Double-Masked, Placebo-Controlled, Parallel-Arm Study to Evaluate the Efficacy and Safety of RZ402 in Participants with Diabetic Macular Edema (DME). A screening period of up to 4 weeks will evaluate eligibility. Once enrolled, patients will be randomized with a 1:1:1:1 ratio to receive RZ402 or placebo for up to 12 weeks. After completing dosing, the patient will enter into a 4 week follow up period.
Interventions
DRUGExperimental: Group 1 - 50mg RZ402
RZ402 50 mg oral tablet, once daily for 3 months
DRUGExperimental: Group 2 - 200mg RZ402
RZ402 200mg oral tablet, once daily for 3 months
DRUGExperimental: Group 3 - 400mg RZ402
RZ402 400mg oral tablet, once daily for 3 months
OTHERPlacebo: Group 4 - Placebo
Placebo oral tablet, once daily for 3 months
Sponsors
Rezolute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria: 1. Confirmed diabetes mellitus Type 1 or Type 2 2. Stable glycemic control Study Eye Inclusion Criteria: 3. Mild to moderate non-proliferative diabetic retinopathy (NPDR) with retinal thickening due to CI-DME as determined by the Investigator. 4. Spectral Domain Optical Coherence Tomography (SD-OCT) foveal CST at screening measuring ≥320 µm (or corresponding values) 5. Best Corrected Visual Acuity ETDRS letter score at 4 meters of ≤78 letters at screening. 6. Media clarity, pupillary dilation, and participant cooperation sufficient for adequate clinical evaluations, OCT images and fundus photographs, at screening. Fellow Eye Inclusion Criteria: 7. Best Corrected Visual Acuity ETDRS letter score at 4 meters of ≥5 letters at screening.
Exclusion criteria
Study Eye
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Central Subfield Thickness in Study Eye | 12 weeks | Change from baseline in Central Subfield Thickness (CST), as measured by Spectral Domain Ocular Coherence Tomography (SD-OCT), compared to placebo. Refer to Study Eye Inclusion/Exclusion Criteria for Study Eye definition. Only one eye was chosen as the Study Eye. In the event both eyes were eligible, the eye with the worse edema (greater CST value) was considered for the purpose of this study as the Study Eye. If both eyes had the same level of edema, the right eye was selected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Best Corrected Visual Acuity in Study Eye | 12 weeks | Change from baseline in Best Corrected Visual Acuity (BCVA) in the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score, compared to placebo. BCVA was assessed by ETDRS chart at 4 meters. This scale is expressed as the total number of ETDRS letters correctly identified at 4 meters. The possible range for the ETDRS BCVA letter score at 4 meters in this study is from 0 to 100 letters (higher scores indicating better visual acuity). Refer to Study Eye Inclusion/Exclusion Criteria for Study Eye definition. Only one eye was chosen as the Study Eye. In the event both eyes were eligible, the eye with the worse edema (greater CST value) was considered for the purpose of this study as the Study Eye. If both eyes had the same level of edema, the right eye was selected. |
| Gain of ≥5 Letters in Best Corrected Visual Acuity in Study Eye | 12 weeks | Number of participants with a gain from baseline of ≥5 letters in BCVA by ETDRS chart at 4 meters, compared to placebo. Refer to Study Eye Inclusion/Exclusion Criteria for Study Eye definition. Only one eye was chosen as the Study Eye. In the event both eyes were eligible, the eye with the worse edema (greater CST value) was considered for the purpose of this study as the Study Eye. If both eyes had the same level of edema, the right eye was selected. |
| Loss of ≥5 Letters in Best Corrected Visual Acuity in Study Eye | 12 weeks | Number of participants with a loss from baseline of ≤5 letters in BCVA by ETDRS chart at 4 meters, compared to placebo. Refer to Study Eye Inclusion/Exclusion Criteria for Study Eye definition. Only one eye was chosen as the Study Eye. In the event both eyes were eligible, the eye with the worse edema (greater CST value) was considered for the purpose of this study as the Study Eye. If both eyes had the same level of edema, the right eye was selected. |
| Change in Diabetic Retinopathy Severity Score | 12 weeks | Change from baseline in Diabetic Retinopathy Severity Score (DRSS), compared to placebo. Color fundus photographs were taken in both eyes at screening and at specified on-site visits to evaluate retinal anatomy and grade DRSS. Fundus photography was conducted pre-dose on applicable visits. A ≥2-step worsening in DRSS markedly increases the likelihood of developing PDR, whereas a ≥2-step improvement in DRSS substantially reduces the incidence of new PDR events compared with sham (approximately three-fold lower). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited based on physician referral. Out of 32 study centers involved in the study, 10 did not enroll participants. The first participant was enrolled on February 6, 2023 and the last participant was enrolled on December 22, 2023.
Pre-assignment details
Of 229 screened participants, 94 met inclusion criteria and were randomized to treatment.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62.13 years STANDARD_DEVIATION 8.33 |
| Best Corrected Visual Acuity, Fellow Eye | 73.87 letters STANDARD_DEVIATION 12.35 |
| Best Corrected Visual Acuity, Study Eye | 69.56 letters STANDARD_DEVIATION 8.81 |
| Body Mass Index | 30.63 kilograms per meter squared STANDARD_DEVIATION 6.78 |
| Central Subfield Thickness <400 µm, Study Eye | 360.10 µm STANDARD_DEVIATION 27.13 |
| Central Subfield Thickness ≥400 µm, Study Eye | 520.00 µm STANDARD_DEVIATION 65.55 |
| Central Subfield Thickness, Fellow Eye | 336.96 µm STANDARD_DEVIATION 62.52 |
| Central Subfield Thickness, Study Eye | 435.43 µm STANDARD_DEVIATION 127.06 |
| Diabetic Retinopathy Severity Scale, Fellow Eye Advanced PDR (Level 85) | 0 Participants |
| Diabetic Retinopathy Severity Scale, Fellow Eye Cannot Grade (Level 90) | 0 Participants |
| Diabetic Retinopathy Severity Scale, Fellow Eye Diabetic retinopathy (DR) Absent (Level 10) | 1 Participants |
| Diabetic Retinopathy Severity Scale, Fellow Eye High-risk PDR (Level 71) | 0 Participants |
| Diabetic Retinopathy Severity Scale, Fellow Eye High-risk PDR (Level 75) | 0 Participants |
| Diabetic Retinopathy Severity Scale, Fellow Eye Microaneurysms Only (Level 20) | 0 Participants |
| Diabetic Retinopathy Severity Scale, Fellow Eye Mild non-proliferative diabetic retinopathy (NPDR) (Level 35) | 11 Participants |
| Diabetic Retinopathy Severity Scale, Fellow Eye Mild proliferative diabetic retinopathy/panretinal photocoagulation (PDR/PRP) Present (Level 61) | 0 Participants |
| Diabetic Retinopathy Severity Scale, Fellow Eye Moderately Severe NPDR | 4 Participants |
| Diabetic Retinopathy Severity Scale, Fellow Eye Moderate NPDR (Level 43) | 4 Participants |
| Diabetic Retinopathy Severity Scale, Fellow Eye Moderate PDR (Level 65) | 2 Participants |
| Diabetic Retinopathy Severity Scale, Fellow Eye Questionable DR (Level 14 or 15) | 0 Participants |
| Diabetic Retinopathy Severity Scale, Fellow Eye Severe NPDR (Level 53) | 0 Participants |
| Diabetic Retinopathy Severity Scale, Study Eye Advanced PDR (Level 85) | 0 Participants |
| Diabetic Retinopathy Severity Scale, Study Eye Cannot Grade (Level 90) | 0 Participants |
| Diabetic Retinopathy Severity Scale, Study Eye Diabetic retinopathy (DR) Absent (Level 10) | 0 Participants |
| Diabetic Retinopathy Severity Scale, Study Eye High-risk PDR (Level 71) | 0 Participants |
| Diabetic Retinopathy Severity Scale, Study Eye High-risk PDR (Level 75) | 0 Participants |
| Diabetic Retinopathy Severity Scale, Study Eye Microaneurysms Only | 1 Participants |
| Diabetic Retinopathy Severity Scale, Study Eye Mild non-proliferative diabetic retinopathy (NPDR) (Level 35) | 14 Participants |
| Diabetic Retinopathy Severity Scale, Study Eye Mild proliferative diabetic retinopathy/panretinal photocoagulation (PDR/PRP) Present (Level 61) | 0 Participants |
| Diabetic Retinopathy Severity Scale, Study Eye Moderately Severe NPDR (Level 47) | 2 Participants |
| Diabetic Retinopathy Severity Scale, Study Eye Moderate NPDR (Level 43) | 23 Participants |
| Diabetic Retinopathy Severity Scale, Study Eye Moderate PDR (Level 65) | 0 Participants |
| Diabetic Retinopathy Severity Scale, Study Eye Questionable DR (Level 14 or 15) | 0 Participants |
| Diabetic Retinopathy Severity Scale, Study Eye Severe NPDR (Level 53) | 0 Participants |
| Duration of Diabetes | 15.92 years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| HbA1C | 7.44 Percentage of glycated hemoglobin STANDARD_DEVIATION 1.14 |
| Height | 170.52 centimeters STANDARD_DEVIATION 8.73 |
| History of prior anti-vascular endothelial growth factor injections Fellow Eye No | 19 Participants |
| History of prior anti-vascular endothelial growth factor injections Fellow Eye Yes | 6 Participants |
| History of prior anti-vascular endothelial growth factor injections Study Eye No | 19 Participants |
| History of prior anti-vascular endothelial growth factor injections Study Eye Yes | 5 Participants |
| Number of anti-vascular endothelial growth factor injections Fellow Eye | 0.48 number of injections STANDARD_DEVIATION 1.07 |
| Number of anti-vascular endothelial growth factor injections Study Eye | 0.52 number of injections STANDARD_DEVIATION 0.99 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Sex: Female, Male Female | 40 Participants |
| Sex: Female, Male Male | 12 Participants |
| Weight | 89.50 kilograms STANDARD_DEVIATION 23.01 |
| Women of Child-bearing Potential No : | 39 Female Participants |
| Women of Child-bearing Potential Yes : | 0 Female Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 12 / 23 | 12 / 23 | 12 / 24 | 11 / 24 |
| serious Total, serious adverse events | 0 / 23 | 1 / 23 | 2 / 24 | 0 / 24 |
Outcome results
None listed