Diabetic RetinopathyPhase 2ZETA-1NCT04692688
Study of the Safety and Efficacy of APX3330 in Diabetic Retinopathy
A Phase 2 study testing APX3330 in people with Diabetic Retinopathy and Diabetic Macular Edema, run by Opus Genetics, Inc at 24 sites in United States.
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). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Diabetic Retinopathy, Diabetic Macular Edema, NPDR - Non Proliferative Diabetic Retinopathy
- What is being tested?
- APX3330
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 103 participants
- Where
- 24 sitesUnited States
- Study dates
- 8 Apr 2021to 25 Jan 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Males or non-pregnant females ≥ 18 years of age
- At least one eye with DR graded at least moderately severe to severe NPDR or mild PDR (corresponding to DRSS 47, 53, or 61)
- BCVA assessed by ETDRS protocol letters score of ≥ 60 letters (Snellen equivalent ≥ 20/63)
- Body mass index (BMI) between 18 and 40 kg/m2, inclusive
Who cannot join
- Ophthalmic:
- Any prior treatment in the study eye with:
- Focal or grid laser photocoagulation within the past year or PRP at any time
- Systemic or intravitreal anti-VEGF agents within the last 6 months
- Intraocular steroids including triamcinolone and dexamethasone implant within the last 6 months
- Fluocinolone implant within the last 3 years
Show all 20Show fewer
- Active uveitis, vitritis, or infection in either eye including infectious conjunctivitis, keratitis, scleritis, or endophthalmitis.
- Ocular incisional surgery including cataract surgery in the study eye within 3 months.
- Clinically significant ocular disease in either eye.
- 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.
- History of retinal detachment, full-thickness macular hole in the study eye, or idiopathic or autoimmune uveitis in either eye.
- Systemic:
- Known hypersensitivity or contraindication to study drug.
- 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.
- 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.
- Resting HR outside the specified range (50-110 beats per minute).
- Known to be immunocompromised or receiving immunosuppressive therapy.
- Hypertension with resting diastolic blood pressure (BP) > 105 mmHg or systolic BP > 200 mmHg.
- History of chronic liver disease or presence of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) consistent with such diagnosis.
- Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control.
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
United States24 sites
Clinical Site 12
Albuquerque, New Mexico, 87113
Clinical Site 18
Austin, Texas, 78705
Clinical Site 8
Bakersfield, California, 93309
Clinical Site 16
Bellaire, Texas, 77030
Clinical Site 5
Beverly Hills, California, 91607
Clinical Site 6
Carmel, Indiana, 46290
Clinical Site 20
Charlotte, North Carolina, 28210
Clinical Site 10
Fort Worth, Texas, 76104
Clinical Site 17
Grand Blanc, Michigan, 48439
Clinical Site 14
Hagerstown, Maryland, 21740
Clinical Site 4
McAllen, Texas, 78550
Clinical Site 19
Miami, Florida, 33143
Clinical Site 21
Ogden, Utah, 84010
Clinical Site 11
Palm Desert, California, 92260
Clinical Site 9
Phoenix, Arizona, 85014
Clinical Site 1
Rapid City, South Dakota, 57701
Clinical Site 2
Sacramento, California, 95825
Clinical Site 3
San Antonio, Texas, 78240
Clinical Site 23
San Antonio, Texas, 78624
Clinical Site 15
Shirley, New York, 11967
Clinical Site 13
Southlake, Texas, 76092
Clinical Site 22
Springfield, Massachusetts, 01107
Clinical Site 24
Walnut Creek, California, 94598
Clinical Site 7
Winter Haven, Florida, 33880
About this study
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
The objective of this study is to evaluate the safety and efficacy of APX3330 to treat diabetic retinopathy (DR) and diabetic macular edema (DME).
Read the 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.
- Conditions
- Diabetic Retinopathy, Diabetic Macular Edema, NPDR - Non Proliferative Diabetic Retinopathy, PDR - Proliferative Diabetic Retinopathy
- Being tested
- APX3330, Placebo
- Keywords
- diabetes, diabetic retinopathy, NPDR, PDR
- Medical subject headings
- Diabetic Retinopathy, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APX3330Drug
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.
PlaceboDrug
Placebo tablets are identical to APX3330 tablets except for the absence of the active pharmaceutical ingredient.
| Study group | Role | What they receive |
|---|---|---|
| APX3330 | Experimental | Five 120 mg tablets will be taken by mouth as follows: 3 tablets every morning and 2 tablets every evening. Receives: Drug: APX3330 |
| Placebo | Placebo comparator | Five 120 mg tablets will be taken by mouth as follows: 3 tablets every morning and 2 tablets every evening. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of Subjects With ≥ 2-step Improvement in Diabetic Retinopathy Severity Score (DRSS)
Percent of subjects with a ≥ 2-step improvement in DRSS from baseline in the study eye (MITT Population- last observation carried forward). 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.
Measured: 24 Weeks
Secondary outcomes (1)
Percent of Subjects With Binocular Improvement or Worsening in DRSS at Week 24
Percent of subjects with Binocular Improvement or worsening in DRSS of ≥ 1, ≥ 2, ≥ 3, and ≥ 4 steps from baseline at Week 24 (MITT Population- Last Observation Carried Forward). 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.
Measured: 24 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2021
- Study start8 Apr 2021
- Primary completion25 Jan 2023
- Study completion25 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic RetinopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Opus Genetics, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04692688
- Sponsor's protocol ID
- OPI-APXDR-201 (ZETA-1)
- Acronym
- ZETA-1
- Status last verified
- Jun 2026
- First submitted
- 29 Dec 2020
- Last updated
- 30 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Lalunio H, Stupka N, Goodman CA, Hayes A. The Potential of Targeting APE1/Ref-1 as a Therapeutic Intervention for Duchenne Muscular Dystrophy. Antioxid Redox Signal. 2025 May;42(13-15):641-654. doi: 10.1089/ars.2024.0620. Epub 2024 Dec 27.
PubMed 39729027
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04692688
- Acronym / sponsor ID
- ZETA-1 / OPI-APXDR-201 (ZETA-1)
- Conditions
- Diabetic Retinopathy, Diabetic Macular Edema, NPDR - Non Proliferative Diabetic Retinopathy, PDR - Proliferative Diabetic Retinopathy
- Keywords
- diabetes, diabetic retinopathy, NPDR, PDR
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Opus Genetics, IncIndustry (pharma, biotech, devices)
- Study start
- 8 Apr 2021 (actual)
- Primary completion
- 25 Jan 2023 (actual)
- Study completion
- 25 Jan 2023 (actual)
- First posted
- 5 Jan 2021 (actual)
- Results
- Posted 8 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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).
| Arm | Type | Receives |
|---|---|---|
| APX3330 | Experimental | Drug: APX3330Five 120 mg tablets will be taken by mouth as follows: 3 tablets every morning and 2 tablets every evening. |
| Placebo | Placebo comparator | Drug: PlaceboFive 120 mg tablets will be taken by mouth as follows: 3 tablets every morning and 2 tablets every evening. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males or non-pregnant females ≥ 18 years of age
- At least one eye with DR graded at least moderately severe to severe NPDR or mild PDR (corresponding to DRSS 47, 53, or 61)
- BCVA assessed by ETDRS protocol letters score of ≥ 60 letters (Snellen equivalent ≥ 20/63)
- Body mass index (BMI) between 18 and 40 kg/m2, inclusive
Key exclusion criteria (20 listed)
- Any prior treatment in the study eye with:
- Active uveitis, vitritis, or infection in either eye including infectious conjunctivitis, keratitis, scleritis, or endophthalmitis.
- Ocular incisional surgery including cataract surgery in the study eye within 3 months.
- Clinically significant ocular disease in either eye.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| APX3330APX3330, a small-molecule oral tablet, is a Ref-1 inhibitor that can potentially reduce proinflammatory and hypoxic signaling that contributes to several eye diseases. | Drug | APX3330 |
| PlaceboPlacebo tablets are identical to APX3330 tablets except for the absence of the active pharmaceutical ingredient. | Drug | Placebo |
Primary outcome
Percent of Subjects With ≥ 2-step Improvement in Diabetic Retinopathy Severity Score (DRSS)
Time frame: 24 Weeks
Percent of subjects with a ≥ 2-step improvement in DRSS from baseline in the study eye (MITT Population- last observation carried forward). 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.
1 secondary outcome
Percent of Subjects With Binocular Improvement or Worsening in DRSS at Week 24
Time frame: 24 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39729027Lalunio H, Stupka N, Goodman CA, Hayes A. The Potential of Targeting APE1/Ref-1 as a Therapeutic Intervention for Duchenne Muscular Dystrophy. Antioxid Redox Signal. 2025 May;42(13-15):641-654. doi: 10.1089/ars.2024.0620. Epub 2024 Dec 27.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing APX3330 in people with Diabetic Retinopathy and Diabetic Macular Edema, run by Opus Genetics, Inc at 24 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent of Subjects With ≥ 2-step Improvement in Diabetic Retinopathy Severity Score (DRSS) (time frame: 24 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04692688, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.