Study of the Safety and Efficacy of APX3330 in Diabetic Retinopathy (ZETA-1)

• ClinicalTrials.gov Identifier: NCT04692688
• Recruitment Status: Active, not recruiting
• First Posted: January 5, 2021
• Last Update Posted: April 29, 2022
• Sponsor: Ocuphire Pharma, Inc.
• Information provided by (Responsible Party): Ocuphire Pharma, Inc.

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Diabetic Retinopathy; Diabetic Macular Edema; NPDR - Non Proliferative Diabetic Retinopathy; PDR - Proliferative Diabetic Retinopathy	Drug: APX3330; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 103 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

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.

• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double-masked
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 8, 2021
• Estimated Primary Completion Date: December 30, 2022
• Estimated Study Completion Date: December 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: APX3330; Five 120 mg tablets will be taken by mouth as follows: 3 tablets every morning and 2 tablets every evening.	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 Comparator: Placebo; Five 120 mg tablets will be taken by mouth as follows: 3 tablets every morning and 2 tablets every evening.	Drug: Placebo; Placebo tablets are identical to APX3330 tablets except for the absence of the active pharmaceutical ingredient.

Outcome Measures

Primary Outcome Measures :

1. Percent of Subjects with an improvement in Diabetic Retinopathy Severity Score (DRSS) [ Time Frame: 24 Weeks ]
   Percent of subjects with a ≥ 2-step improvement in DRSS in the study eye

Secondary Outcome Measures :

1. Percent of Subjects with change in Diabetic Retinopathy Severity Scale (DRSS) Scores [ Time Frame: 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
2. Mean Change in Diabetic Retinopathy Severity Scale (DRSS) Score [ Time Frame: 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.
3. Percent of Subjects without DR/DME Disease Progression [ Time Frame: 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
4. Mean Change in Best-Corrected Visual Acuity (BCVA) [ Time Frame: 24 Weeks ]
   Mean change in BCVA at Week 24
5. Mean Change in Central Subfield Thickness (CST) [ Time Frame: 24 Weeks ]
   Mean Change in CST at Week 24

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

United States, Arizona

Clinical Site 9

Phoenix, Arizona, United States, 85014

United States, California

Clinical Site 8

Bakersfield, California, United States, 93309

Clinical Site 5

Beverly Hills, California, United States, 91607

Clinical Site 11

Palm Desert, California, United States, 92260

Clinical Site 2

Sacramento, California, United States, 95825

Clinical Site 24

Walnut Creek, California, United States, 94598

United States, Florida

Clinical Site 19

Miami, Florida, United States, 33143

Clinical Site 7

Winter Haven, Florida, United States, 33880

United States, Indiana

Clinical Site 6

Carmel, Indiana, United States, 46290

United States, Maryland

Clinical Site 14

Hagerstown, Maryland, United States, 21740

United States, Massachusetts

Clinical Site 22

Springfield, Massachusetts, United States, 01107

United States, Michigan

Clinical Site 17

Grand Blanc, Michigan, United States, 48439

United States, New Mexico

Clinical Site 12

Albuquerque, New Mexico, United States, 87113

United States, New York

Clinical Site 15

Shirley, New York, United States, 11967

United States, North Carolina

Clinical Site 20

Charlotte, North Carolina, United States, 28210

United States, South Dakota

Clinical Site 1

Rapid City, South Dakota, United States, 57701

United States, Texas

Clinical Site 18

Austin, Texas, United States, 78705

Clinical Site 16

Bellaire, Texas, United States, 77030

Clinical Site 10

Fort Worth, Texas, United States, 76104

Clinical Site 4

McAllen, Texas, United States, 78550

Clinical Site 3

San Antonio, Texas, United States, 78240

Clinical Site 23

San Antonio, Texas, United States, 78624

Clinical Site 13

Southlake, Texas, United States, 76092

United States, Utah

Clinical Site 21

Ogden, Utah, United States, 84010

Sponsors and Collaborators

Ocuphire Pharma, Inc.

More Information

• Responsible Party: Ocuphire Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT04692688
• Other Study ID Numbers: OPI-APXDR-201 (ZETA-1)
• First Posted: January 5, 2021
• Last Update Posted: April 29, 2022
• Last Verified: March 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ocuphire Pharma, Inc.:

diabetes; diabetic retinopathy; NPDR; PDR

Additional relevant MeSH terms:

Macular Edema; Retinal Diseases; Diabetic Retinopathy; Diabetes Mellitus; Endocrine System Diseases; Macular Degeneration; Retinal Degeneration; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications