Diabetic Macular Edema, Diabetic Retinopathy, NPDR - Non Proliferative Diabetic Retinopathy, PDR - Proliferative Diabetic Retinopathy
Conditions
Keywords
diabetes, diabetic retinopathy, NPDR, PDR
Brief summary
The objective of this study is to evaluate the safety and efficacy of APX3330 to treat diabetic retinopathy (DR) and diabetic macular edema (DME).
Detailed description
The objective of this study is to evaluate the efficacy of APX3330 to improve Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Score (DRSS) in one hundred (100) subjects with moderately severe to severe NPDR or mild PDR. Subjects with moderately severe to severe NPDR and mild PDR will be selected for study participation and be screened for study eligibility. The eligible eye with the highest DRSS, as assessed by the central reading center, will be designated as the study eye for the primary efficacy analysis. If the subject meets all eligibility criteria, then the subject will be randomized into the study and receive study medication. Blood will be drawn for biomarker analysis. The total length of subject participation is approximately 26 weeks, with 5 clinic visits, 4 telephone safety calls, and one telephone call follow-up visit. The execution of the entire study (first subject screen through last randomized subject completed) is expected to be approximately 12 to 15 months.
Interventions
DRUGAPX3330
APX3330, a small-molecule oral tablet, is a Ref-1 inhibitor that can potentially reduce proinflammatory and hypoxic signaling that contributes to several eye diseases.
DRUGPlacebo
Placebo tablets are identical to APX3330 tablets except for the absence of the active pharmaceutical ingredient.
Sponsors
Ocuphire Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-masked
Intervention model description
This is a placebo-controlled, double-masked, randomized, Phase 2 study in approximately 100 subjects with moderately severe to severe non-proliferative diabetic retinopathy (NPDR), or mild proliferative diabetic retinopathy (PDR), evaluating safety and efficacy following administration of APX3330 twice daily for 24 weeks. The study will have a 1:1 randomization (placebo: APX3330).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Males or non-pregnant females ≥ 18 years of age 2. At least one eye with DR graded at least moderately severe to severe NPDR or mild PDR (corresponding to DRSS 47, 53, or 61) 3. BCVA assessed by ETDRS protocol letters score of ≥ 60 letters (Snellen equivalent ≥ 20/63) 4. Body mass index (BMI) between 18 and 40 kg/m2, inclusive
Exclusion criteria
Ophthalmic: 1. Any prior treatment in the study eye with: 1. Focal or grid laser photocoagulation within the past year or PRP at any time 2. Systemic or intravitreal anti-VEGF agents within the last 6 months 3. Intraocular steroids including triamcinolone and dexamethasone implant within the last 6 months 4. Fluocinolone implant within the last 3 years 2. Active uveitis, vitritis, or infection in either eye including infectious conjunctivitis, keratitis, scleritis, or endophthalmitis. 3. Ocular incisional surgery including cataract surgery in the study eye within 3 months. 4. Clinically significant ocular disease in either eye. 5. Presence of macular or retinal vascular disease including diabetic macular edema, retinopathy from causes other than diabetes, age-related macular degeneration, pattern dystrophy, choroidal neovascularization of any cause, retinal vein occlusion, retinal artery occlusion in the study eye. 6. History of retinal detachment, full-thickness macular hole in the study eye, or idiopathic or autoimmune uveitis in either eye. Systemic: 1. Known hypersensitivity or contraindication to study drug. 2. Any disease or medical condition that in the opinion of the Investigator would interfere with the study, prevent the subject from successfully participating in the study, or which might confound the study results. 3. Participation in any investigational study within 30 days prior to screening or planning to participate in any other investigational drug or device clinical trials within 30 days of study completion. 4. Resting HR outside the specified range (50-110 beats per minute). 5. Known to be immunocompromised or receiving immunosuppressive therapy. 6. Hypertension with resting diastolic blood pressure (BP) \> 105 mmHg or systolic BP \> 200 mmHg. 7. History of chronic liver disease or presence of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) consistent with such diagnosis. 8. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects With ≥ 2-step Improvement in Diabetic Retinopathy Severity Score (DRSS) | 24 Weeks | Percent of subjects with a ≥ 2-step improvement in DRSS from baseline in the study eye (MITT Population- last observation carried forward). DRSS is scored on a range from 10 to 90 with 13 discrete scores given within that range and where higher scores indicate a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects With Binocular Improvement or Worsening in DRSS at Week 24 | 24 Weeks | Percent of subjects with Binocular Improvement or worsening in DRSS of ≥ 1, ≥ 2, ≥ 3, and ≥ 4 steps from baseline at Week 24 (MITT Population- Last Observation Carried Forward). DRSS is scored on a range from 10 to 90 with 13 discrete scores given within that range and where higher scores indicate a worse outcome. |
Countries
United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 58.3 years STANDARD_DEVIATION 9.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 77 Participants |
| Region of Enrollment United States | 98 participants |
| Sex: Female, Male Female | 50 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 1 / 52 |
| other Total, other adverse events | 13 / 51 | 21 / 52 |
| serious Total, serious adverse events | 4 / 51 | 12 / 52 |
Outcome results
None listed