Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04692688
Recruitment Status : Active, not recruiting
First Posted : January 5, 2021
Last Update Posted : April 29, 2022
Sponsor:
Information provided by (Responsible Party):
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).

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.

Layout table for study information
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

Resource links provided by the National Library of Medicine


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.




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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04692688


Locations
Show Show 24 study locations
Sponsors and Collaborators
Ocuphire Pharma, Inc.
Layout table for additonal information
Responsible Party: Ocuphire Pharma, Inc.
ClinicalTrials.gov Identifier: NCT04692688    
Other Study ID Numbers: OPI-APXDR-201 (ZETA-1)
First Posted: January 5, 2021    Key Record Dates
Last Update Posted: April 29, 2022
Last Verified: March 2022

Layout table for additional information
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:
Layout table for 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