Diabetic Macular EdemaPhase 1/2NCT03397264

A Dose Ranging Study of OPT-302 With Aflibercept for Persistent Diabetic Macular Edema

A Phase 1/2 study testing Aflibercept and OPT-302 in people with Diabetic Macular Edema, run by Opthea Limited at 53 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

A two part, multi-center study consisting of a Phase 1b open label, sequential dose escalation followed by a Phase 2a randomized, double-masked, dose expansion evaluating OPT-302 in combination with aflibercept in participants with persistent central-involved Diabetic Macular Edema. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Diabetic Macular Edema
What is being tested?: Aflibercept and OPT-302
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 153 participants
Where: 53 sitesin 4 countries
Study dates: 16 Jan 2018to 11 Jun 2020
Phase: Phase 1/2
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
No healthy volunteers
Adult, Older adult

Who may be able to join

History of diabetic macular edema (DME) ≤ 2 year
Persistent DME despite prior intravitreal anti-VEGF-A therapy with a sub-optimal response
Three or more prior anti-VEGF-A therapy intravitreal injections
EDTRS BCVA score ≤ 73 and ≥ 24 letters

Who cannot join

Ocular disorders or ocular treatments which may interfere with assessment of visual acuity, assessment of toxicity, or fundus photography in the Study Eye
HbA1c ≥ 12% and/or recent signs of uncontrolled diabetes
Any clinically significant disorder or condition or disease (e.g. cardiovascular, renal conditions) that would make the participant unsuitable for the study

Trial locations and contacts

53 sites in 4 countries.

Country

City, postcode or hospital

53 sites in 4 countries

United States34 sites

Opthea Investigational Site
Abilene, Texas, 79606
Opthea Investigational Site
Arlington, Texas, 76012
Opthea Investigational Site
Asheville, North Carolina, 28803
Opthea Investigational Site
Augusta, Georgia, 30909
Opthea Investigational Site
Austin, Texas, 78705
Opthea Investigational Site
Bakersfield, California, 93309
Opthea Investigational Site
Beverly Hills, California, 90211
Opthea Investigational Site
Boynton Beach, Florida, 33426
Opthea Investigational Site
Charleston, South Carolina, 29414
Opthea Investigational Site
Charlotte, North Carolina, 28210
Opthea Investigational Site
Colorado Springs, Colorado, 30909
Opthea Investigational Site
Des Moines, Iowa, 50266
Opthea Investigational Site
Fort Myers, Florida, 33912
Opthea Investigational Site
Germantown, Tennessee, 38138
Opthea Investigational Site
Hagerstown, Maryland, 21740
Opthea Investigational Site
Houston, Texas, 77030
Opthea Investigational Site
Indianapolis, Indiana, 46290
Opthea Investigational Site
Las Vegas, Nevada, 89144
Opthea Investigational Site
McAllen, Texas, 78503
Opthea Investigational Site
Melbourne, Florida, 32901
Opthea Investigational Site
Pensacola, Florida, 32503
Opthea Investigational Site
Phoenix, Arizona, 85014
Opthea Investigational Site
Portland, Oregon, 97213
Opthea Investigational Site
Rapid City, South Dakota, 57701
Opthea Investigational Site
Redlands, California, 92374
Opthea Investigational Site
Reno, Nevada, 89502
Opthea Investigational Site
Sacramento, California, 95819
Opthea Investigational Site
San Antonio, Texas, 78240
Opthea Investigational Site
Santa Ana, California, 92705
Opthea Investigational Site
St. Petersburg, Florida, 33711
Opthea Investigational Site
West Columbia, South Carolina, 29169
Opthea Investigational Site
Wichita, Kansas, 67214
Opthea Investigational Site
Willow Park, Texas, 76087
Opthea Investigational Site
Youngstown, Ohio, 92705

Other trials in United States

Israel11 sites

Opthea Investigational Site
Be’er Ya‘aqov, 703 5
Opthea Investigational Site
Haifa, 31048
Opthea Investigational Site
Haifa, 31096
Opthea Investigational Site
Haifa, 34362
Opthea Investigational Site
Jerusalem, 91031
Opthea Investigational Site
Jerusalem, 91120
Opthea Investigational Site
Kfar Saba, 44281
Opthea Investigational Site
Petah Tikva, 49100
Opthea Investigational Site
Rehovot, 76100
Opthea Investigational Site
Tel Aviv, 64239
Opthea Investigational Site
Tiberias, 15208

Other trials in Israel

Australia4 sites

Opthea Investigational Site
Parramatta, New South Wales
Opthea Investigational Site
Perth, Western Australia
Opthea Investigational Site
Sydney, New South Wales
Opthea Investigational Site
Westmead, New South Wales, 2145

Other trials in Australia

Latvia4 sites

Opthea Investigational Site
Jelgava, LV-3001
Opthea Investigational Site
Riga, LV-1002
Opthea Investigational Site
Riga, LV-1006
Opthea Investigational Site
Riga, LV-1050

Other trials in Latvia

About this study

Official title: Phase 1b/2a Study of OPT-302 in Combination With Aflibercept for Persistent Central-involved Diabetic Macular Edema

Read the detailed description

Study OPT-302-1003 was designed as a 2-part, multicenter study consisting of a Phase 1b open-label, sequential dose escalation followed by a Phase 2a randomized, parallel-group, sham-controlled, double-masked, dose-expansion evaluating intravitreal OPT-302 in combination with aflibercept in participants with persistent central-involved diabetic macula edema.

Conditions: Diabetic Macular Edema
Being tested: Aflibercept, OPT-302, Sham intravitreal injection

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AfliberceptBiological
Also called Eylea
Intravitreal injection
OPT-302Biological
Intravitreal Injection
Sham intravitreal injectionOther
Sham (mock) intravitreal injection

Study groups in NCT03397264
Study group	Role	What they receive
Ph 1b: 2.0 mg aflibercept with 0.3 mg OPT-302	Experimental	2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 0.3 mg OPT-302 intravitreal injection (0.05 mL) Receives: Biological: Aflibercept; Biological: OPT-302
Ph 1b: 2.0 mg aflibercept with 1.0 mg OPT-302	Experimental	2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 1.0 mg OPT-302 intravitreal injection (0.05 mL) Receives: Biological: Aflibercept; Biological: OPT-302
Ph 1b: 2.0 mg aflibercept with 2.0 mg OPT-302	Experimental	2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 2.0 mg OPT-302 intravitreal injection (0.05 mL) Receives: Biological: Aflibercept; Biological: OPT-302
Ph 2a: 2.0 mg aflibercept with 2.0 mg OPT-302	Experimental	2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 2.0 mg OPT-302 intravitreal injection (0.05 mL) Receives: Biological: Aflibercept; Biological: OPT-302
Ph 2a: 2.0 mg aflibercept with sham	Sham comparator	2.0 mg aflibercept intravitreal injection (0.05 mL) followed by sham intravitreal injection Receives: Biological: Aflibercept; Other: Sham intravitreal injection

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Safety and Tolerability will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events and CTC v4.0 (if available, otherwise protocol defined grading were used)
Measured: Baseline to Week 12
Phase 2a: Response Rate Defined as Proportion of Participants Receiving OPT-302 With Aflibercept Achieving at Least a 5-letter Gain in BCVA at Week 12
Change from baseline in Best Corrected Visual Acuity (BCVA) will be measured at Week 12 according to Early Treatment Diabetic Retinopathy Score (ETDRS) criteria
Measured: Baseline to Week 12

Secondary outcomes (2)

Mean Change in BCVA
Mean change in Best Corrected Visual Acuity (BCVA). BCVA will be measured according to Early Treatment Diabetic Retinopathy Score (ETDRS) criteria
Measured: Baseline to Week 12
Mean Change in CST
Mean change in central subfield thickness (CST) on spectral domain coherence tomography (SD-OCT)
Measured: Baseline to Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Jan 201811 Jun 2020

First posted11 Jan 2018
Study start16 Jan 2018
Primary completion26 Mar 2020
Study completion11 Jun 2020

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.
Other trials for Diabetic Macular EdemaStudies 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 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Phase 1b - sequential dose followed by Phase 2a - parallel arm
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 153 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03397264
Sponsor's protocol ID: OPT-302-1003
Status last verified: Apr 2025
First submitted: 1 Jan 2018
Last updated: 22 Apr 2025
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingObservational study
Real World Evidence in China: Faricimab Use in Diabetic Macular Edema, Retinal Vein Occlusion, and Neovascular Age-Related Macular Degeneration (The Farseeing Study)
Diabetic Macular Edema, Neovascular Age-related Macular Degeneration
Active, not recruitingPhase 2
Long-Term Follow-Up Study of RGX-314 Administered in the Suprachoroidal Space for Participants With and Without Diabetic Retinopathy
Diabetic Retinopathy, DR
RecruitingPhase 3
A Phase 3 Trial for Intravitreal Injection of 4D-150 in Adults With Diabetic Macular Edema (DME).
Diabetic Macular Edema (DME)
RecruitingPhase 2
Oral N-Acetylcysteine on Diabetic Macular Edema
Diabetic Macular Edema (DME)
Active, not recruitingPhase 3
COMO: A Phase 3 Randomized, Double-Masked Study Comparing the Efficacy of EYP-1901 Against Aflibercept in DME
Diabetic Macular Edema, DME

All Diabetic Macular Edema trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 1b/2a Study of OPT-302 in Combination With Aflibercept for Persistent Central-involved Diabetic Macular Edema
ClinicalTrials.gov ID: NCT03397264
Acronym / sponsor ID: OPT-302-1003
Conditions: Diabetic Macular Edema
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 153 participants (actual)
Lead sponsor: Opthea LimitedIndustry (pharma, biotech, devices)
Study start: 16 Jan 2018 (actual)
Primary completion: 26 Mar 2020 (actual)
Study completion: 11 Jun 2020 (actual)
First posted: 11 Jan 2018 (actual)
Results: Posted 22 Jun 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5
Model description: Phase 1b - sequential dose followed by Phase 2a - parallel arm

Arm	Type	Receives
Ph 1b: 2.0 mg aflibercept with 0.3 mg OPT-302	Experimental	Biological: Aflibercept, Biological: OPT-3022.0 mg aflibercept intravitreal injection (0.05 mL) followed by 0.3 mg OPT-302 intravitreal injection (0.05 mL)
Ph 1b: 2.0 mg aflibercept with 1.0 mg OPT-302	Experimental	Biological: Aflibercept, Biological: OPT-3022.0 mg aflibercept intravitreal injection (0.05 mL) followed by 1.0 mg OPT-302 intravitreal injection (0.05 mL)
Ph 1b: 2.0 mg aflibercept with 2.0 mg OPT-302	Experimental	Biological: Aflibercept, Biological: OPT-3022.0 mg aflibercept intravitreal injection (0.05 mL) followed by 2.0 mg OPT-302 intravitreal injection (0.05 mL)
Ph 2a: 2.0 mg aflibercept with 2.0 mg OPT-302	Experimental	Biological: Aflibercept, Biological: OPT-3022.0 mg aflibercept intravitreal injection (0.05 mL) followed by 2.0 mg OPT-302 intravitreal injection (0.05 mL)
Ph 2a: 2.0 mg aflibercept with sham	Sham comparator	Biological: Aflibercept, Other: Sham intravitreal injection2.0 mg aflibercept intravitreal injection (0.05 mL) followed by sham intravitreal injection

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

History of diabetic macular edema (DME) ≤ 2 year
Persistent DME despite prior intravitreal anti-VEGF-A therapy with a sub-optimal response
Three or more prior anti-VEGF-A therapy intravitreal injections
EDTRS BCVA score ≤ 73 and ≥ 24 letters

Key exclusion criteria (3 listed)

Ocular disorders or ocular treatments which may interfere with assessment of visual acuity, assessment of toxicity, or fundus photography in the Study Eye
HbA1c ≥ 12% and/or recent signs of uncontrolled diabetes
Any clinically significant disorder or condition or disease (e.g. cardiovascular, renal conditions) that would make the participant unsuitable for the study

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
AfliberceptAlso: EyleaIntravitreal injection	Biological	Ph 1b: 2.0 mg aflibercept with 0.3 mg OPT-302, Ph 1b: 2.0 mg aflibercept with 1.0 mg OPT-302, Ph 1b: 2.0 mg aflibercept with 2.0 mg OPT-302, Ph 2a: 2.0 mg aflibercept with 2.0 mg OPT-302, Ph 2a: 2.0 mg aflibercept with sham
OPT-302Intravitreal Injection	Biological	Ph 1b: 2.0 mg aflibercept with 0.3 mg OPT-302, Ph 1b: 2.0 mg aflibercept with 1.0 mg OPT-302, Ph 1b: 2.0 mg aflibercept with 2.0 mg OPT-302, Ph 2a: 2.0 mg aflibercept with 2.0 mg OPT-302
Sham intravitreal injectionSham (mock) intravitreal injection	Other	Ph 2a: 2.0 mg aflibercept with sham

Primary outcome

Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Time frame: Baseline to Week 12
Safety and Tolerability will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events and CTC v4.0 (if available, otherwise protocol defined grading were used)
Phase 2a: Response Rate Defined as Proportion of Participants Receiving OPT-302 With Aflibercept Achieving at Least a 5-letter Gain in BCVA at Week 12
Time frame: Baseline to Week 12
Change from baseline in Best Corrected Visual Acuity (BCVA) will be measured at Week 12 according to Early Treatment Diabetic Retinopathy Score (ETDRS) criteria

2 secondary outcomes

Mean Change in BCVA
Time frame: Baseline to Week 12
Mean Change in CST
Time frame: Baseline to Week 12

Results and safety

Results posted to the registry on 22 Jun 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ph 1b: 2.0 mg Aflibercept With 0.3 mg OPT-302	3	3
Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-302	3	3
Ph 1b: 2.0 mg Aflibercept With 2.0 mg OPT-302	3	3
Ph 2a: 2.0 mg Aflibercept With 2.0 mg OPT-302	96	89
Ph 2a: 2.0 mg Aflibercept With Sham	48	47

Primary outcome: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

Time frame: Baseline to Week 12. Count of participants. Unit: Participants

Measure	Ph 1b: 2.0 mg Aflibercept With 0.3 mg OPT-302 n = 3	Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-302 n = 3	Ph 1b: 2.0 mg Aflibercept With 2.0 mg OPT-302 n = 3	Ph 2a: 2.0 mg Aflibercept With 2.0 mg OPT-302 n = 95	Ph 2a: 2.0 mg Aflibercept With Sham n = 49
Treatment Emergent AE to Wk 12	3	2	1	59	28
Ocular Treatment Emergent AEs to Wk 12	2	2	1	43	16
Non-ocular Treatment Emergnt AEs to Wk 12	2	2	0	35	17
Ocular SAEs to Wk 12	0	0	0	0	0
Non Ocular SAEs to Wk 12	1	1	0	8	1

Population analysed: Safety Population; Ph2a: One participant assigned 2.0 mg OPT-302 with aflibercept did not receive OPT-302 therefore this participant was analyzed as part of the sham combination for the safety analysis only.

Primary outcome: Phase 2a: Response Rate Defined as Proportion of Participants Receiving OPT-302 With Aflibercept Achieving at Least a 5-letter Gain in BCVA at Week 12

Time frame: Baseline to Week 12. Count of participants. Unit: Participants

Measure	Ph 2a: 2.0 mg Aflibercept With 2.0 mg OPT-302 n = 72
Value	38

Population analysed: Primary Analysis (pre-specified) OPT-302 combination therapy will be considered to have clinical activity if \>= 27 of 72 participants have a \>= 5 letters gain in BCVA from baseline to week 12. The combination therapy will be considered to have insufficient clinical activity if \<= 25 of 72 participants have a \>= 5 letters gain in BCVA from baseline to week 12.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline to Week 12. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ph 1b: 2.0 mg Aflibercept With 0.3 mg OPT-302	1 of 3 (33.3%)	2 of 3 (66.7%)	0 of 3
Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-302	1 of 3 (33.3%)	1 of 3 (33.3%)	0 of 3
Ph 1b: 2.0 mg Aflibercept With 2.0 mg OPT-302	0 of 3 (0%)	1 of 3 (33.3%)	0 of 3
Ph 2a: 2.0 mg Aflibercept With 2.0 mg OPT-302	8 of 95 (8.4%)	36 of 95 (37.9%)	0 of 95
Ph 2a: 2.0 mg Aflibercept With Sham	1 of 49 (2%)	15 of 49 (30.6%)	0 of 49

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Diabetic Macular Edema

Active, not recruitingObservational study
Real World Evidence in China: Faricimab Use in Diabetic Macular Edema, Retinal Vein Occlusion, and Neovascular Age-Related Macular Degeneration (The Farseeing Study)
Diabetic Macular Edema, Neovascular Age-related Macular Degeneration
Active, not recruitingPhase 2
Long-Term Follow-Up Study of RGX-314 Administered in the Suprachoroidal Space for Participants With and Without Diabetic Retinopathy
Diabetic Retinopathy, DR
RecruitingPhase 3
A Phase 3 Trial for Intravitreal Injection of 4D-150 in Adults With Diabetic Macular Edema (DME).
Diabetic Macular Edema (DME)
RecruitingPhase 2
Oral N-Acetylcysteine on Diabetic Macular Edema
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Active, not recruitingPhase 3
COMO: A Phase 3 Randomized, Double-Masked Study Comparing the Efficacy of EYP-1901 Against Aflibercept in DME
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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.

Study Director Opthea study director

Opthea Limited

53 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Aflibercept and OPT-302 in people with Diabetic Macular Edema, run by Opthea Limited at 53 sites in 4 countries.

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 3 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 22 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in United States, Israel, Australia, Latvia. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 22 Jun 2022). 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?

Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) (time frame: Baseline to Week 12). The study lists 2 primary outcomes in all. 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 NCT03397264.

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 22 Apr 2025.