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CompletedNCT03397264Updated Apr 22, 2025Results posted

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

A Phase 1/2 interventional study of Aflibercept and OPT-302 in Diabetic Macular Edema, sponsored by Opthea Limited. Completed at 53 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-04-22.

Sponsored by Opthea Limited · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
153
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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 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.

02

Conditions studied

  • Diabetic Macular Edema
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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

Exclusion criteria

Exclusion Criteria:

  • 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
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
153 participants (actual)

Study arms

  • Experimental
    Ph 1b: 2.0 mg aflibercept with 0.3 mg OPT-302

    2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 0.3 mg OPT-302 intravitreal injection (0.05 mL)

    Biological: Aflibercept · Biological: OPT-302

  • Experimental
    Ph 1b: 2.0 mg aflibercept with 1.0 mg OPT-302

    2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 1.0 mg OPT-302 intravitreal injection (0.05 mL)

    Biological: Aflibercept · Biological: OPT-302

  • Experimental
    Ph 1b: 2.0 mg aflibercept with 2.0 mg OPT-302

    2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 2.0 mg OPT-302 intravitreal injection (0.05 mL)

    Biological: Aflibercept · Biological: OPT-302

  • Experimental
    Ph 2a: 2.0 mg aflibercept with 2.0 mg OPT-302

    2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 2.0 mg OPT-302 intravitreal injection (0.05 mL)

    Biological: Aflibercept · Biological: OPT-302

  • Sham comparator
    Ph 2a: 2.0 mg aflibercept with sham

    2.0 mg aflibercept intravitreal injection (0.05 mL) followed by sham intravitreal injection

    Biological: Aflibercept · Other: Sham intravitreal injection

Interventions

  • BiologicalAflibercept

    Intravitreal injection

    Also known as: Eylea

  • BiologicalOPT-302

    Intravitreal Injection

  • OtherSham intravitreal injection

    Sham (mock) intravitreal injection

05

What researchers measure

Primary outcomes

  1. 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)

    Time frame: Baseline to Week 12

  2. 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

    Time frame: Baseline to Week 12

Secondary outcomes

  1. 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

    Time frame: Baseline to Week 12

  2. Mean Change in CST

    Mean change in central subfield thickness (CST) on spectral domain coherence tomography (SD-OCT)

    Time frame: Baseline to Week 12

06

Results

Posted Jun 22, 2022

Participant flow

Participant flow — Overall Study
MilestonePh 1b: 2.0 mg Aflibercept With 0.3 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With Sham
Started3339648
Completed3338947
Not completed00071

Outcome measures

PrimaryIncidence 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)

Time frame:
Baseline to Week 12
Reported as:
Count of participants · Participants
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
ParticipantsPh 1b: 2.0 mg Aflibercept With 0.3 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With Sham
Treatment Emergent AE to Wk 123215928
Ocular Treatment Emergent AEs to Wk 122214316
Non-ocular Treatment Emergnt AEs to Wk 122203517
Ocular SAEs to Wk 1200000
Non Ocular SAEs to Wk 1211081
PrimaryPhase 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

Time frame:
Baseline to Week 12
Reported as:
Count of participants · Participants
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
ParticipantsPh 2a: 2.0 mg Aflibercept With 2.0 mg OPT-302
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 1238
SecondaryMean Change in BCVA

Mean change in Best Corrected Visual Acuity (BCVA). BCVA will be measured according to Early Treatment Diabetic Retinopathy Score (ETDRS) criteria

Time frame:
Baseline to Week 12
Reported as:
Mean · Letters
Mean Change in BCVA
LettersPh 1b: 2.0 mg Aflibercept With 0.3 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With Sham
Mean Change in BCVA3.0 ± 2.525.7 ± 1.2014.3 ± 5.465.9 ± 0.796.1 ± 0.96
SecondaryMean Change in CST

Mean change in central subfield thickness (CST) on spectral domain coherence tomography (SD-OCT)

Time frame:
Baseline to Week 12
Reported as:
Mean · µm
Mean Change in CST
µmPh 1b: 2.0 mg Aflibercept With 0.3 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With Sham
Mean Change in CST-116.0 ± 46.12-41.0 ± 28.88-57.0 ± 12.86-52.2 ± 10.28-34.9 ± 12.01

Adverse events

Collected over Baseline to Week 12. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Ph 1b: 2.0 mg Aflibercept With 0.3 mg OPT-3020/3 (0%)1/3 (33.3%)2/3 (66.7%)
Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-3020/3 (0%)1/3 (33.3%)1/3 (33.3%)
Ph 1b: 2.0 mg Aflibercept With 2.0 mg OPT-3020/3 (0%)0/3 (0%)1/3 (33.3%)
Ph 2a: 2.0 mg Aflibercept With 2.0 mg OPT-3020/95 (0%)8/95 (8.4%)36/95 (37.9%)
Ph 2a: 2.0 mg Aflibercept With Sham0/49 (0%)1/49 (2%)15/49 (30.6%)
Most frequent serious events
Showing 10 of 15
Most frequent serious events
EventPh 1b: 2.0 mg Aflibercept With 0.3 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With Sham
NephrolithiasisRenal and urinary disorders1/30/30/30/950/49
Impaired Gastric EmptyingGastrointestinal disorders0/31/30/30/950/49
PneumoniaInfections and infestations0/30/30/32/950/49
HypoglycemiaMetabolism and nutrition disorders0/30/30/30/951/49
Postoperative Wound InfectionInfections and infestations0/30/30/31/950/49
HyponatremiaMetabolism and nutrition disorders0/30/30/31/950/49
Acute Kidney InjuryRenal and urinary disorders0/30/30/31/950/49
UlcerGeneral disorders0/30/30/31/950/49
Cerebrovascular AccidentNervous system disorders0/30/30/31/950/49
Acute Respiratory FailureRespiratory, thoracic and mediastinal disorders0/30/30/31/950/49
Most frequent other events
Most frequent other events
EventPh 1b: 2.0 mg Aflibercept With 0.3 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With Sham
Conjunctival HaemorrhageEye disorders1/31/31/319/956/49
Punctate KeratitisEye disorders1/30/30/32/953/49
Intraocular Pressure IncreasedEye disorders0/30/30/313/953/49
BronchitisInfections and infestations0/30/30/32/953/49

Baseline characteristics

Safety Analysis Population

Age, Categorical
Age, Categorical(Participants)Ph 1b: 2.0 mg Aflibercept With 0.3 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With ShamTotal
<=18 years000000
Between 18 and 65 years213583296
>=65 years120381657
Age, Continuous
Age, Continuous(years)Ph 1b: 2.0 mg Aflibercept With 0.3 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With ShamTotal
Ph 1b59.0 ± 6.2468.7 ± 7.5155.7 ± 7.02——61.1 ± 8.39
Ph 2a———61.8 ± 10.0761.2 ± 9.4061.6 ± 9.93
Sex: Female, Male
Sex: Female, Male(Participants)Ph 1b: 2.0 mg Aflibercept With 0.3 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With ShamTotal
Female110361856
Male223603097
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Ph 1b: 2.0 mg Aflibercept With 0.3 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With ShamTotal
American Indian or Alaska Native000000
Asian000112
Native Hawaiian or Other Pacific Islander000000
Black or African American0108817
White3238737132
More than one race000000
Unknown or Not Reported000022
Region of Enrollment
Region of Enrollment(participants)Ph 1b: 2.0 mg Aflibercept With 0.3 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With ShamTotal
Latvia000639
United States333613192
Israel000241034
Australia000549
Baseline ETDRS Best Corrected Visual Acuity
Baseline ETDRS Best Corrected Visual Acuity(Letters read)Ph 1b: 2.0 mg Aflibercept With 0.3 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-302Ph 1b: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With 2.0 mg OPT-302Ph 2a: 2.0 mg Aflibercept With ShamTotal
Mean64.3 ± 7.0264.7 ± 1.5366.0 ± 8.8963.3 ± 8.3163.9 ± 9.4463.5 ± 8.68
07

Study locations

53 sites
  • Opthea Investigational Site
    Phoenix, Arizona 85014, United States
  • Opthea Investigational Site
    Bakersfield, California 93309, United States
  • Opthea Investigational Site
    Beverly Hills, California 90211, United States
  • Opthea Investigational Site
    Redlands, California 92374, United States
  • Opthea Investigational Site
    Sacramento, California 95819, United States
  • Opthea Investigational Site
    Santa Ana, California 92705, United States
  • Opthea Investigational Site
    Colorado Springs, Colorado 30909, United States
  • Opthea Investigational Site
    Boynton Beach, Florida 33426, United States
  • Opthea Investigational Site
    Fort Myers, Florida 33912, United States
  • Opthea Investigational Site
    Melbourne, Florida 32901, United States
  • Opthea Investigational Site
    Pensacola, Florida 32503, United States
  • Opthea Investigational Site
    Saint Petersburg, Florida 33711, United States
  • Opthea Investigational Site
    Augusta, Georgia 30909, United States
  • Opthea Investigational Site
    Indianapolis, Indiana 46290, United States
  • Opthea Investigational Site
    Des Moines, Iowa 50266, United States
  • Opthea Investigational Site
    Wichita, Kansas 67214, United States
  • Opthea Investigational Site
    Hagerstown, Maryland 21740, United States
  • Opthea Investigational Site
    Las Vegas, Nevada 89144, United States
  • Opthea Investigational Site
    Reno, Nevada 89502, United States
  • Opthea Investigational Site
    Asheville, North Carolina 28803, United States
  • Opthea Investigational Site
    Charlotte, North Carolina 28210, United States
  • Opthea Investigational Site
    Youngstown, Ohio 92705, United States
  • Opthea Investigational Site
    Portland, Oregon 97213, United States
  • Opthea Investigational Site
    Charleston, South Carolina 29414, United States
  • Opthea Investigational Site
    West Columbia, South Carolina 29169, United States
  • Opthea Investigational Site
    Rapid City, South Dakota 57701, United States
  • Opthea Investigational Site
    Germantown, Tennessee 38138, United States
  • Opthea Investigational Site
    Abilene, Texas 79606, United States
  • Opthea Investigational Site
    Arlington, Texas 76012, United States
  • Opthea Investigational Site
    Austin, Texas 78705, United States
  • Opthea Investigational Site
    Houston, Texas 77030, United States
  • Opthea Investigational Site
    McAllen, Texas 78503, United States
  • Opthea Investigational Site
    San Antonio, Texas 78240, United States
  • Opthea Investigational Site
    Willow Park, Texas 76087, United States
  • Opthea Investigational Site
    Parramatta, New South Wales, Australia
  • Opthea Investigational Site
    Sydney, New South Wales, Australia
  • Opthea Investigational Site
    Westmead, New South Wales 2145, Australia
  • Opthea Investigational Site
    Perth, Western Australia, Australia
  • Opthea Investigational Site
    Be'er Ya'aqov, 703 5, Israel
  • Opthea Investigational Site
    Haifa, 31048, Israel
  • Opthea Investigational Site
    Haifa, 31096, Israel
  • Opthea Investigational Site
    Haifa, 34362, Israel
  • Opthea Investigational Site
    Jerusalem, 91031, Israel
  • Opthea Investigational Site
    Jerusalem, 91120, Israel
  • Opthea Investigational Site
    Kfar Saba, 44281, Israel
  • Opthea Investigational Site
    Petah Tikva, 49100, Israel
  • Opthea Investigational Site
    Reẖovot, 76100, Israel
  • Opthea Investigational Site
    Tel Aviv Yafo, 64239, Israel
  • Opthea Investigational Site
    Tiberias, 15208, Israel
  • Opthea Investigational Site
    Jelgava, LV-3001, Latvia
  • Opthea Investigational Site
    Riga, LV-1002, Latvia
  • Opthea Investigational Site
    Riga, LV-1006, Latvia
  • Opthea Investigational Site
    Riga, LV-1050, Latvia
08

References and documents

Study documents

  • Study protocol · Aug 2, 2018
  • Statistical analysis plan · May 18, 2020

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03397264
Lead sponsor
Opthea Limited
Responsible party
Sponsor
First posted
Jan 11, 2018
Start date
Jan 16, 2018
Primary completion
Mar 26, 2020
Completion
Jun 11, 2020
Results posted
Jun 22, 2022
Last update
Apr 22, 2025

Study contacts

Study Director Opthea
study director · Opthea Limited

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
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