Study of the Safety and Efficacy of APX3330 in Diabetic Retinopathy

Diabetic Retinopathy Clinical Trial

— ZETA-1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04692688
• Other study ID #: OPI-APXDR-201 (ZETA-1)
• Status: Completed
• Phase: Phase 2
• Start date: April 8, 2021
• Est. completion date: January 25, 2023

Study information

• Verified date: February 2023
• Source: Ocuphire Pharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: January 25, 2023
• Est. primary completion date: January 25, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetic Macular Edema
• Diabetic Retinopathy
• Macular Edema
• NPDR - Non Proliferative Diabetic Retinopathy
• PDR - Proliferative Diabetic Retinopathy
• Retinal Diseases

Intervention

Drug:
• APX3330
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.
• Placebo
Placebo tablets are identical to APX3330 tablets except for the absence of the active pharmaceutical ingredient.

Locations

Country	Name	City	State
United States	Clinical Site 12	Albuquerque	New Mexico
United States	Clinical Site 18	Austin	Texas
United States	Clinical Site 8	Bakersfield	California
United States	Clinical Site 16	Bellaire	Texas
United States	Clinical Site 5	Beverly Hills	California
United States	Clinical Site 6	Carmel	Indiana
United States	Clinical Site 20	Charlotte	North Carolina
United States	Clinical Site 10	Fort Worth	Texas
United States	Clinical Site 17	Grand Blanc	Michigan
United States	Clinical Site 14	Hagerstown	Maryland
United States	Clinical Site 4	McAllen	Texas
United States	Clinical Site 19	Miami	Florida
United States	Clinical Site 21	Ogden	Utah
United States	Clinical Site 11	Palm Desert	California
United States	Clinical Site 9	Phoenix	Arizona
United States	Clinical Site 1	Rapid City	South Dakota
United States	Clinical Site 2	Sacramento	California
United States	Clinical Site 23	San Antonio	Texas
United States	Clinical Site 3	San Antonio	Texas
United States	Clinical Site 15	Shirley	New York
United States	Clinical Site 13	Southlake	Texas
United States	Clinical Site 22	Springfield	Massachusetts
United States	Clinical Site 24	Walnut Creek	California
United States	Clinical Site 7	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Ocuphire Pharma, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of Subjects with an improvement in Diabetic Retinopathy Severity Score (DRSS)	Percent of subjects with a = 2-step improvement in DRSS in the study eye	24 Weeks
Secondary	Percent of Subjects with change in Diabetic Retinopathy Severity Scale (DRSS) Scores	Percent of subjects with an improvement or worsening in DRSS of = 1, = 2, = 3, and = 4 steps at Week 12 and Week 24	Up to 24 Weeks
Secondary	Mean Change in Diabetic Retinopathy Severity Scale (DRSS) Score	Mean change from baseline in DRSS at Week 24. 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.	24 Weeks
Secondary	Percent of Subjects without DR/DME Disease Progression	Percent of subjects not developing center-involved DME or moderate PDR or PDR-related AEs during the study at Week 12 and Week 24	24 Weeks
Secondary	Mean Change in Best-Corrected Visual Acuity (BCVA)	Mean change in BCVA at Week 24	24 Weeks
Secondary	Mean Change in Central Subfield Thickness (CST)	Mean Change in CST at Week 24	24 Weeks