Study of the Safety and Efficacy of APX3330 in Diabetic Retinopathy

Phase 2

Completed

• Conditions: Diabetic Retinopathy; Diabetic Macular Edema; NPDR - Non Proliferative Diabetic Retinopathy; PDR - Proliferative Diabetic Retinopathy
• Interventions: Drug: APX3330; Drug: Placebo

• Registration Number: NCT04692688
• Lead Sponsor: Ocuphire Pharma, Inc.

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.

Study Timeline

• Study First Submitted: 2020-12-29
• Study First Submitted QC: 2020-12-29
• Study First Posted: 2021-01-05
• Study Start: 2021-04-08
• Primary Completion: 2023-01-25
• Study Completion: 2023-01-25
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-24
• Last Update Posted: 2023-02-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 103

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
APX3330	APX3330	Five 120 mg tablets will be taken by mouth as follows: 3 tablets every morning and 2 tablets every evening.
Placebo	Placebo	Five 120 mg tablets will be taken by mouth as follows: 3 tablets every morning and 2 tablets every evening.

Primary Outcome Measures

Name	Time	Method
Percent of Subjects with an improvement in Diabetic Retinopathy Severity Score (DRSS)	24 Weeks	Percent of subjects with a ≥ 2-step improvement in DRSS in the study eye

Secondary Outcome Measures

Name	Time	Method
Percent of Subjects without DR/DME Disease Progression	24 Weeks	Percent of subjects not developing center-involved DME or moderate PDR or PDR-related AEs during the study at Week 12 and Week 24
Percent of Subjects with change in Diabetic Retinopathy Severity Scale (DRSS) Scores	Up to 24 Weeks	Percent of subjects with an improvement or worsening in DRSS of ≥ 1, ≥ 2, ≥ 3, and ≥ 4 steps at Week 12 and Week 24
Mean Change in Diabetic Retinopathy Severity Scale (DRSS) Score	24 Weeks	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.
Mean Change in Best-Corrected Visual Acuity (BCVA)	24 Weeks	Mean change in BCVA at Week 24
Mean Change in Central Subfield Thickness (CST)	24 Weeks	Mean Change in CST at Week 24

Trial Locations

Locations (24)

Clinical Site 11; 🇺🇸 Palm Desert, California, United States

Clinical Site 5; 🇺🇸 Beverly Hills, California, United States

Clinical Site 9; 🇺🇸 Phoenix, Arizona, United States

Clinical Site 24; 🇺🇸 Walnut Creek, California, United States

Clinical Site 7; 🇺🇸 Winter Haven, Florida, United States

Clinical Site 22; 🇺🇸 Springfield, Massachusetts, United States

Clinical Site 12; 🇺🇸 Albuquerque, New Mexico, United States

Clinical Site 1; 🇺🇸 Rapid City, South Dakota, United States

Clinical Site 20; 🇺🇸 Charlotte, North Carolina, United States

Clinical Site 18; 🇺🇸 Austin, Texas, United States

Clinical Site 10; 🇺🇸 Fort Worth, Texas, United States

Clinical Site 4; 🇺🇸 McAllen, Texas, United States

Clinical Site 13; 🇺🇸 Southlake, Texas, United States

Clinical Site 8; 🇺🇸 Bakersfield, California, United States

Clinical Site 2; 🇺🇸 Sacramento, California, United States

Clinical Site 19; 🇺🇸 Miami, Florida, United States

Clinical Site 6; 🇺🇸 Carmel, Indiana, United States

Clinical Site 14; 🇺🇸 Hagerstown, Maryland, United States

Clinical Site 3; 🇺🇸 San Antonio, Texas, United States

Clinical Site 23; 🇺🇸 San Antonio, Texas, United States

Clinical Site 21; 🇺🇸 Ogden, Utah, United States

Clinical Site 17; 🇺🇸 Grand Blanc, Michigan, United States

Clinical Site 15; 🇺🇸 Shirley, New York, United States

Clinical Site 16; 🇺🇸 Bellaire, Texas, United States