Clinical trial NCT04692688: Study of the Safety and Efficacy of APX3330 in Diabetic Retinopathy
Official title: Randomized, Placebo-Controlled, Double-Masked Study of the Safety and Efficacy of Orally Administered APX3330 in Subjects With Moderately Severe to Severe Non-Proliferative Diabetic Retinopathy and Mild Proliferative Diabetic Retinopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Retinopathy
Diabetic Macular Edema
NPDR - Non Proliferative Diabetic Retinopathy
PDR - Proliferative Diabetic Retinopathy
Keywords: diabetes
diabetic retinopathy
NPDR
PDR
Lead sponsor: Ocuphire Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2021-01-05
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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). Randomization will be stratified by level of disease severity (NPDR or PDR). Subjects with mild PDR will be capped at 20% for each arm.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent of Subjects with an improvement in Diabetic Retinopathy Severity Score (DRSS)
timeFrame: 24 Weeks
Secondary outcomes:
measure: Percent of Subjects with change in Diabetic Retinopathy Severity Scale (DRSS) Scores
timeFrame: Up to 24 Weeks
measure: Mean Change in Diabetic Retinopathy Severity Scale (DRSS) Score
timeFrame: 24 Weeks
measure: Percent of Subjects without DR/DME Disease Progression
timeFrame: 24 Weeks
measure: Mean Change in Best-Corrected Visual Acuity (BCVA)
timeFrame: 24 Weeks
measure: Mean Change in Central Subfield Thickness (CST)
timeFrame: 24 Weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Clinical Site 9
state: Arizona
city: Bakersfield
country: United States
facility: Clinical Site 8
state: California
city: Beverly Hills
country: United States
facility: Clinical Site 5
state: California
city: Palm Desert
country: United States
facility: Clinical Site 11
state: California
city: Sacramento
country: United States
facility: Clinical Site 2
state: California
city: Walnut Creek
country: United States
facility: Clinical Site 24
state: California
city: Miami
country: United States
facility: Clinical Site 19
state: Florida
city: Winter Haven
country: United States
facility: Clinical Site 7
state: Florida
city: Carmel
country: United States
facility: Clinical Site 6
state: Indiana
city: Hagerstown
country: United States
facility: Clinical Site 14
state: Maryland
city: Springfield
country: United States
facility: Clinical Site 22
state: Massachusetts
city: Grand Blanc
country: United States
facility: Clinical Site 17
state: Michigan
city: Albuquerque
country: United States
facility: Clinical Site 12
state: New Mexico
city: Shirley
country: United States
facility: Clinical Site 15
state: New York
city: Charlotte
country: United States
facility: Clinical Site 20
state: North Carolina
city: Rapid City
country: United States
facility: Clinical Site 1
state: South Dakota
city: Austin
country: United States
facility: Clinical Site 18
state: Texas
city: Bellaire
country: United States
facility: Clinical Site 16
state: Texas
city: Fort Worth
country: United States
facility: Clinical Site 10
state: Texas
city: McAllen
country: United States
facility: Clinical Site 4
state: Texas
city: San Antonio
country: United States
facility: Clinical Site 3
state: Texas
city: San Antonio
country: United States
facility: Clinical Site 23
state: Texas
city: Southlake
country: United States
facility: Clinical Site 13
state: Texas
city: Ogden
country: United States
facility: Clinical Site 21
state: Utah
Study officials:
References: