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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
|
| 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) |
|
| 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) |
|
| 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) |
|
| Ph 2a: 2.0 mg aflibercept with sham | Sham Comparator | 2.0 mg aflibercept intravitreal injection (0.05 mL) followed by sham intravitreal injection |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aflibercept | Biological | Intravitreal injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 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 | Baseline to Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Baseline to Week 12 |
| Mean Change in CST |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director Opthea | Opthea Limited | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Opthea Investigational Site | Phoenix | Arizona | 85014 | United States | ||
| Opthea Investigational Site |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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) Aflibercept: Intravitreal injection OPT-302: Intravitreal Injection |
| FG001 | Ph 1b: 2.0 mg Aflibercept With 1.0 mg OPT-302 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 2, 2018 | Aug 18, 2021 |
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Phase 1b - sequential dose followed by Phase 2a - parallel arm
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Ph 1b open label; Ph 2a quadruple masked
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| OPT-302 | Biological | Intravitreal Injection |
|
| Sham intravitreal injection | Other | Sham (mock) intravitreal injection |
|
Mean change in central subfield thickness (CST) on spectral domain coherence tomography (SD-OCT)
| Baseline to Week 12 |
| 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 | St. 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 | Rehovot | 76100 | Israel |
| Opthea Investigational Site | Tel Aviv | 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 |
2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 1.0 mg OPT-302 intravitreal injection (0.05 mL) Aflibercept: Intravitreal injection OPT-302: Intravitreal Injection |
| FG002 | 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) Aflibercept: Intravitreal injection OPT-302: Intravitreal Injection |
| FG003 | 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) Aflibercept: Intravitreal injection OPT-302: Intravitreal Injection |
| FG004 | Ph 2a: 2.0 mg Aflibercept With Sham | 2.0 mg aflibercept intravitreal injection (0.05 mL) followed by sham intravitreal injection Aflibercept: Intravitreal injection Sham intravitreal injection: Sham (mock) intravitreal injection |
| COMPLETED | Completed the Treatment Phase to Week 12 |
|
| NOT COMPLETED |
|
Safety Analysis Population
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| ID | Title | Description |
|---|---|---|
| BG000 | 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) Aflibercept: Intravitreal injection OPT-302: Intravitreal Injection |
| BG001 | 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) Aflibercept: Intravitreal injection OPT-302: Intravitreal Injection |
| BG002 | 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) Aflibercept: Intravitreal injection OPT-302: Intravitreal Injection |
| BG003 | 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) Aflibercept: Intravitreal injection OPT-302: Intravitreal Injection |
| BG004 | Ph 2a: 2.0 mg Aflibercept With Sham | 2.0 mg aflibercept intravitreal injection (0.05 mL) followed by sham intravitreal injection Aflibercept: Intravitreal injection Sham intravitreal injection: Sham (mock) intravitreal injection |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| |||||||||||
| Age, Continuous | Ph1b and Ph2a studies were two separate studies within the one protocol. Combined mean age across the two studies was not calculated. | Mean | Standard Deviation | years |
| |||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| |||||||||||
| Region of Enrollment | Number | participants |
| |||||||||||
| Baseline ETDRS Best Corrected Visual Acuity | Mean | Standard Deviation | Letters read |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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) | 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. | Posted | Count of Participants | Participants | Baseline to Week 12 |
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| Primary | 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 | 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. | Posted | Count of Participants | Participants | No | Baseline to Week 12 |
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| Secondary | 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 | Per Protocol Population | Posted | Mean | Standard Error | Letters | Baseline to Week 12 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change in CST | Mean change in central subfield thickness (CST) on spectral domain coherence tomography (SD-OCT) | Per Protocol Population; and where CST measurements at Week 12 were available to assess the endpoint. | Posted | Mean | Standard Error | µm | Baseline to Week 12 |
|
Baseline to Week 12
Ph2a: One participant assigned 2.0 mg OPT-302 with aflibercept did not receive OPT-302 therefore this participant was analysed as part of the sham combination for the safety analysis only.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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) Aflibercept: Intravitreal injection OPT-302: Intravitreal Injection | 0 | 3 | 1 | 3 | 2 | 3 |
| EG001 | 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) Aflibercept: Intravitreal injection OPT-302: Intravitreal Injection | 0 | 3 | 1 | 3 | 1 | 3 |
| EG002 | 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) Aflibercept: Intravitreal injection OPT-302: Intravitreal Injection | 0 | 3 | 0 | 3 | 1 | 3 |
| EG003 | 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) Aflibercept: Intravitreal injection OPT-302: Intravitreal Injection | 0 | 95 | 8 | 95 | 36 | 95 |
| EG004 | Ph 2a: 2.0 mg Aflibercept With Sham | 2.0 mg aflibercept intravitreal injection (0.05 mL) followed by sham intravitreal injection Aflibercept: Intravitreal injection Sham intravitreal injection: Sham (mock) intravitreal injection | 0 | 49 | 1 | 49 | 15 | 49 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA 20.1 | Non-systematic Assessment |
| |
| Postoperative Wound Infection | Infections and infestations | MedDRA 20.1 | Non-systematic Assessment |
| |
| Hypoglycemia | Metabolism and nutrition disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Hyponatremia | Metabolism and nutrition disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Acute Kidney Injury | Renal and urinary disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Nephrolithiasis | Renal and urinary disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Impaired Gastric Emptying | Gastrointestinal disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Ulcer | General disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Cerebrovascular Accident | Nervous system disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Acute Respiratory Failure | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Pulmonary Edema | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Cardiac Failure Congestive | Cardiac disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Coronary Artery Disease | Cardiac disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Ocular SAE | Eye disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Conjunctival Haemorrhage | Eye disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Intraocular Pressure Increased | Eye disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Punctate Keratitis | Eye disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA 20.1 | Non-systematic Assessment |
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The Principal Investigator may publish data or results from the Study; provided the Principal Investigator submits the proposed publication to Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary and/or commercially sensitive to the Sponsor.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director of Clinical Research | Opthea | +61 3 9826 0399 | info@opthea.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 18, 2020 | Aug 18, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C533178 | aflibercept |
| C005703 | salicylhydroxamic acid |
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| Ph 2a |
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| United States |
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| Israel |
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| Australia |
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| Ocular Treatment Emergent AEs to Wk 12 |
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| Non-ocular Treatment Emergnt AEs to Wk 12 |
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| Ocular SAEs to Wk 12 |
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| Non Ocular SAEs to Wk 12 |
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2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 2.0 mg OPT-302 intravitreal injection (0.05 mL) Aflibercept: Intravitreal injection OPT-302: Intravitreal Injection |
| OG004 | Ph 2a: 2.0 mg Aflibercept With Sham | 2.0 mg aflibercept intravitreal injection (0.05 mL) followed by sham intravitreal injection Aflibercept: Intravitreal injection Sham intravitreal injection: Sham (mock) intravitreal injection |
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2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 2.0 mg OPT-302 intravitreal injection (0.05 mL) Aflibercept: Intravitreal injection OPT-302: Intravitreal Injection |
| OG004 | Ph 2a: 2.0 mg Aflibercept With Sham | 2.0 mg aflibercept intravitreal injection (0.05 mL) followed by sham intravitreal injection Aflibercept: Intravitreal injection Sham intravitreal injection: Sham (mock) intravitreal injection |
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