Nonproliferative Diabetic Retinopathy
Conditions
Keywords
NPDR, EYP-1901, EyePoint
Brief summary
A prospective, randomized, double-masked study that evaluated the ocular efficacy and safety of two doses of the EYP-1901 intravitreal (IVT) insert compared to sham.
Detailed description
This study evaluated the ocular efficacy and safety of two doses of the EYP-1901 IVT insert compared to sham using a randomized double-masked trial design.
Interventions
DRUGEYP-1901
EYP-1901 will be administered to the study eye by a single injection through the pars plana using a pre-loaded applicator with a 22-gauge needle. Each EYP-1901 IVT insert has been designed to deliver vorolanib into the vitreous humor for approximately 6 to 9 months.
OTHERSham IVT
Sham injections will be used to maintain masking of investigational EYP-1901 therapy for study subjects.
Sponsors
EyePoint Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have a hemoglobin A1c \<=12% * Study eye with moderately severe to severe Non proliferative Diabetic Retinopathy (NPDR) (based on the Diabetic Retinopathy Severity Scale (DRSS) levels 47 or 53) * Best corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) letter score in the study eye of \>=69 letters (approximate Snellen equivalent of 20/40 or better).
Exclusion criteria
* Presence of any active Center involved-diabetic macular edema in the study eye as determined by the Investigator on clinical examination, or within the central subfield thickness (CST) of the study eye, with a CST threshold greater than 320 microns. * Any evidence or documented history of prior focal or grid laser photocoagulation or any pan-retinal photocoagulation (PRP) in the study eye in the last 12 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Improved >=2 Steps From Baseline in the DRSS Score at Week 36 | Baseline (Day 1) and Week 36 | The DRSS used to describe overall retinopathy severity as well as the change in severity over time in the study eye. Severity ranges from level 10 (diabetic retinopathy absent) to level 85 (advanced proliferative diabetic retinopathy (PDR): posterior fundus obscured, or center of macula detached). Here, DRSS describes severity level 47 (moderately severe NPDR) and level 53 (severe NPDR) at Week 36 from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | Baseline (Day 1) and Weeks 24, 36 and 48 | The DRSS used to describe overall retinopathy severity as well as the change in severity over time in the study eye. Severity ranges from level 10 (diabetic retinopathy absent) to level 85 (advanced PDR: posterior fundus obscured, or center of macula detached). Here, DRSS describes severity level 47 (moderately severe NPDR) and level 53 (severe NPDR) at Weeks 24, 36 and 48 from baseline. |
| Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | Baseline (Day 1) and Weeks 24, 36 and 48 | The DRSS used to describe overall retinopathy severity as well as the change in severity over time in the study eye. Severity ranges from level 10 (diabetic retinopathy absent) to level 85 (advanced PDR: posterior fundus obscured, or center of macula detached). Here, DRSS describes severity level 47 (moderately severe NPDR) and level 53 (severe NPDR) at Weeks 24, 36 and 48 from baseline. |
| Percentage of Subjects Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Weeks 24, 36 and 48 | Weeks 24, 36 and 48 | The vision threatening complications in the study eye due to diabetic retinopathy were indicated by the presence of Vitreous hemorrhage or the presence of Tractional retinal detachment reported on the Ocular Examination - Dilated Ophthalmoscopy CRF (PDR events), and Neovascularization for the Iris answered as Yes or Neovascularization for the Angle answered as Yes per the Ocular Examination - Slit Lamp Biomicroscopy CRF (anterior segment neovascularization (ASNV) events). |
| Percentage of Subjects Who Developed Center Involved-Diabetic Macular Edema (CI-DME) at Weeks 24, 36 and 48 | Weeks 24, 36 and 48 | The CI-DME in the study eye occurred when a treatment emergent adverse event (TEAE) with a mapped preferred term of 'Cystoid macular oedema', 'Diabetic retinal oedema', or 'Macular oedema' occurred in the study eye, in combination with the temporally closest centrally read custom algorithm CST measurement being greater than or equal to 320 microns. |
| Time to Develop Any Neovascular Vision Threatening Complication (PDR/ASNV) at Weeks 24, 36 and 48 | Weeks 24, 36 and 48 | Time to develop any PDR/ASNV was computed as the date of the first development of PDR/ASNV in the study eye minus the date of study treatment administration plus 1 day, divided by 7 days per week. |
| Percentage of Subjects Improved >=2 Steps From Baseline in the DRSS Score at Week 24 and Week 48 | Baseline (Day 1), Week 24, and Week 48 | The DRSS used to describe overall retinopathy severity as well as the change in severity over time in the study eye. Severity ranges from level 10 (diabetic retinopathy absent) to level 85 (advanced proliferative diabetic retinopathy (PDR): posterior fundus obscured, or center of macula detached). Here, DRSS describes severity levels 47 (moderately severe NPDR) and 53 (severe NPDR) at Weeks 24 and 48 from baseline. |
| Percentage of Subjects Who Received Anti-Vascular Endothelial Growth Factor (VEGF) or Additional Standard of Care Intervention Due to Ocular Diabetic Complications at Weeks 24, 36 and 48 | Weeks 24, 36 and 48 | Percentage of subjects who received anti-VEGF or additional standard of care intervention due to ocular diabetic complications in the study eye are reported. Anti-VEGF use was identified in reported concomitant medication data. |
| Percentage of Subjects Who Received PRP at Weeks 24, 36 and 48 | Weeks 24, 36 and 48 | Percentage of subjects who received PRP in the study eye, inclusive of subjects undergoing vitrectomy with endo-laser are reported. |
| Area Under the Curve (AUC) for Change From Baseline in BCVA at Weeks 24, 36 and 48 | Weeks 24, 36 and 48 | The AUC for change from baseline in BCVA in the study eye were summarized. The AUC through each time point of interest was computed using the trapezoidal rule normalized to months, with a final unit of letters. |
| Plasma Concentration of EYP-1901 and X-297 at Weeks 24, 36 and 48 | Weeks 24, 36 and 48 | Blood samples were collected at the specific visits for the Pharmacokinetic (PK) analysis of EYP-1901 and its main metabolite concentrations. |
| Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | TEAEs were collected from the study drug administration (Day 1) up to end of the study, approximately 48 weeks. | An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational or marketed (medicinal) product and that does not necessarily have a causal relationship with the product. A serious AE is any AE that results in one of the following outcomes: death; life-threatening; requires in-patient hospitalization; results in a persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. The TEAEs are AEs that occur after the first dose of study treatment administration. |
| Time to Develop CI-DME Through Weeks 24, 36 and 48 | Weeks 24, 36 and 48 | The occurrence of a CI-DME event in the study eye was identified via examination of centrally read custom algorithm CST data and adverse events. |
Countries
United States
Participant flow
Recruitment details
This Phase 2 prospective, randomized, double-masked study was conducted in adult subjects with NPDR at 25 sites in the United States between 28 September 2022 and 06 May 2024.
Pre-assignment details
This study consists of a screening period (up to 30 days) and treatment period (48 weeks). A total of 77 subjects were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Sham Injection Subjects received a single dose of sham IVT injection on Day 1. | 26 |
| EYP-1901 2060 mcg Subjects received a single dose of EYP-1901 2060 mcg IVT injection on Day 1. | 26 |
| EYP-1901 3090 mcg Subjects received a single dose of EYP-1901 3090 mcg IVT injection on Day 1. | 25 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event: Non-ocular | 0 | 1 | 0 |
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 1 | 4 |
| Overall Study | Other | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | Sham Injection | Total | EYP-1901 3090 mcg | EYP-1901 2060 mcg |
|---|---|---|---|---|
| Age, Continuous | 56.9 years STANDARD_DEVIATION 11.95 | 57.9 years STANDARD_DEVIATION 11.26 | 60.2 years STANDARD_DEVIATION 9.98 | 56.8 years STANDARD_DEVIATION 11.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 25 Participants | 8 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 50 Participants | 17 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 4 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 9 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 4 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 21 Participants | 58 Participants | 18 Participants | 19 Participants |
| Sex: Female, Male Female | 13 Participants | 34 Participants | 9 Participants | 12 Participants |
| Sex: Female, Male Male | 13 Participants | 43 Participants | 16 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 26 | 1 / 26 | 0 / 26 | 0 / 26 | 1 / 26 | 0 / 25 | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 7 / 26 | 5 / 26 | 9 / 26 | 8 / 26 | 8 / 26 | 14 / 26 | 8 / 25 | 5 / 25 | 7 / 25 |
| serious Total, serious adverse events | 1 / 26 | 1 / 26 | 2 / 26 | 1 / 26 | 1 / 26 | 7 / 26 | 0 / 25 | 0 / 25 | 1 / 25 |
Outcome results
Primary
Percentage of Subjects Improved >=2 Steps From Baseline in the DRSS Score at Week 36
The DRSS used to describe overall retinopathy severity as well as the change in severity over time in the study eye. Severity ranges from level 10 (diabetic retinopathy absent) to level 85 (advanced proliferative diabetic retinopathy (PDR): posterior fundus obscured, or center of macula detached). Here, DRSS describes severity level 47 (moderately severe NPDR) and level 53 (severe NPDR) at Week 36 from baseline.
Time frame: Baseline (Day 1) and Week 36
Population: The FAS included all subjects who received at least 1 dose of study treatment (EYP-1901 or sham).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sham Injection | Percentage of Subjects Improved >=2 Steps From Baseline in the DRSS Score at Week 36 | 5.0 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Improved >=2 Steps From Baseline in the DRSS Score at Week 36 | 0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Improved >=2 Steps From Baseline in the DRSS Score at Week 36 | 4.8 percentage of subjects |
95% CI: [-24.9, 13.4]
95% CI: [-20.6, 20.6]
Secondary
Area Under the Curve (AUC) for Change From Baseline in BCVA at Weeks 24, 36 and 48
The AUC for change from baseline in BCVA in the study eye were summarized. The AUC through each time point of interest was computed using the trapezoidal rule normalized to months, with a final unit of letters.
Time frame: Weeks 24, 36 and 48
Population: The FAS included all subjects who received at least 1 dose of study treatment (EYP-1901 or sham).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham Injection | Area Under the Curve (AUC) for Change From Baseline in BCVA at Weeks 24, 36 and 48 | Week 36 | -0.23 letters | Standard Deviation 3.234 |
| Sham Injection | Area Under the Curve (AUC) for Change From Baseline in BCVA at Weeks 24, 36 and 48 | Week 24 | -0.32 letters | Standard Deviation 2.969 |
| Sham Injection | Area Under the Curve (AUC) for Change From Baseline in BCVA at Weeks 24, 36 and 48 | Week 48 | -0.38 letters | Standard Deviation 3.127 |
| EYP-1901 2060 mcg | Area Under the Curve (AUC) for Change From Baseline in BCVA at Weeks 24, 36 and 48 | Week 36 | -1.52 letters | Standard Deviation 6.819 |
| EYP-1901 2060 mcg | Area Under the Curve (AUC) for Change From Baseline in BCVA at Weeks 24, 36 and 48 | Week 24 | -1.58 letters | Standard Deviation 8.411 |
| EYP-1901 2060 mcg | Area Under the Curve (AUC) for Change From Baseline in BCVA at Weeks 24, 36 and 48 | Week 48 | -1.44 letters | Standard Deviation 6.369 |
| EYP-1901 3090 mcg | Area Under the Curve (AUC) for Change From Baseline in BCVA at Weeks 24, 36 and 48 | Week 24 | 0.46 letters | Standard Deviation 4.07 |
| EYP-1901 3090 mcg | Area Under the Curve (AUC) for Change From Baseline in BCVA at Weeks 24, 36 and 48 | Week 48 | -0.02 letters | Standard Deviation 5.311 |
| EYP-1901 3090 mcg | Area Under the Curve (AUC) for Change From Baseline in BCVA at Weeks 24, 36 and 48 | Week 36 | 0.03 letters | Standard Deviation 4.562 |
Secondary
Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48
An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational or marketed (medicinal) product and that does not necessarily have a causal relationship with the product. A serious AE is any AE that results in one of the following outcomes: death; life-threatening; requires in-patient hospitalization; results in a persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. The TEAEs are AEs that occur after the first dose of study treatment administration.
Time frame: TEAEs were collected from the study drug administration (Day 1) up to end of the study, approximately 48 weeks.
Population: The Safety set included all subjects who received at least 1 dose of study treatment (EYP-1901 or sham).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sham Injection | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any TEAE | 7 Participants |
| Sham Injection | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any Serious TEAE | 1 Participants |
| EYP-1901 2060 mcg | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any TEAE | 9 Participants |
| EYP-1901 2060 mcg | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any Serious TEAE | 1 Participants |
| EYP-1901 3090 mcg | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any TEAE | 15 Participants |
| EYP-1901 3090 mcg | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any Serious TEAE | 2 Participants |
| EYP-1901 2060 mcg (Week 48) | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any TEAE | 7 Participants |
| EYP-1901 2060 mcg (Week 48) | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any Serious TEAE | 1 Participants |
| EYP-1901 3090 mcg (Week 24) | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any TEAE | 8 Participants |
| EYP-1901 3090 mcg (Week 24) | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any Serious TEAE | 1 Participants |
| EYP-1901 3090 mcg (Week 48) | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any Serious TEAE | 7 Participants |
| EYP-1901 3090 mcg (Week 48) | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any TEAE | 16 Participants |
| EYP-1901 3090 mcg - Study Eye | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any Serious TEAE | 0 Participants |
| EYP-1901 3090 mcg - Study Eye | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any TEAE | 11 Participants |
| EYP-1901 3090 mcg - Non-study Eye | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any TEAE | 7 Participants |
| EYP-1901 3090 mcg - Non-study Eye | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any Serious TEAE | 0 Participants |
| EYP-1901 3090 mcg - Non-ocular | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any TEAE | 12 Participants |
| EYP-1901 3090 mcg - Non-ocular | Number of Subjects With Ocular and Non-Ocular TEAEs and Serious TEAEs up to Week 48 | Any Serious TEAE | 1 Participants |
Secondary
Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48
The DRSS used to describe overall retinopathy severity as well as the change in severity over time in the study eye. Severity ranges from level 10 (diabetic retinopathy absent) to level 85 (advanced PDR: posterior fundus obscured, or center of macula detached). Here, DRSS describes severity level 47 (moderately severe NPDR) and level 53 (severe NPDR) at Weeks 24, 36 and 48 from baseline.
Time frame: Baseline (Day 1) and Weeks 24, 36 and 48
Population: The FAS included all subjects who received at least 1 dose of study treatment (EYP-1901 or sham). Only subjects analyzed at specific timepoints are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sham Injection | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step improvement in DRSS: Week 24 | 0 percentage of subjects |
| Sham Injection | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step improvement in DRSS: Week 36 | 5.0 percentage of subjects |
| Sham Injection | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step improvement in DRSS: Week 48 | 0 percentage of subjects |
| Sham Injection | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step improvement in DRSS: Week 24 | 0 percentage of subjects |
| Sham Injection | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step improvement in DRSS: Week 36 | 0 percentage of subjects |
| Sham Injection | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step improvement in DRSS: Week 48 | 0 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step improvement in DRSS: Week 48 | 0 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step improvement in DRSS: Week 24 | 0 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step improvement in DRSS: Week 24 | 0 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step improvement in DRSS: Week 36 | 0 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step improvement in DRSS: Week 36 | 0 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step improvement in DRSS: Week 48 | 0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step improvement in DRSS: Week 36 | 4.8 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step improvement in DRSS: Week 48 | 5.3 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step improvement in DRSS: Week 48 | 0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step improvement in DRSS: Week 24 | 0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step improvement in DRSS: Week 24 | 0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Improved >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step improvement in DRSS: Week 36 | 0 percentage of subjects |
Secondary
Percentage of Subjects Improved >=2 Steps From Baseline in the DRSS Score at Week 24 and Week 48
The DRSS used to describe overall retinopathy severity as well as the change in severity over time in the study eye. Severity ranges from level 10 (diabetic retinopathy absent) to level 85 (advanced proliferative diabetic retinopathy (PDR): posterior fundus obscured, or center of macula detached). Here, DRSS describes severity levels 47 (moderately severe NPDR) and 53 (severe NPDR) at Weeks 24 and 48 from baseline.
Time frame: Baseline (Day 1), Week 24, and Week 48
Population: The FAS included all subjects who received at least 1 dose of study treatment (EYP-1901 or sham).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sham Injection | Percentage of Subjects Improved >=2 Steps From Baseline in the DRSS Score at Week 24 and Week 48 | 0 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Improved >=2 Steps From Baseline in the DRSS Score at Week 24 and Week 48 | 0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Improved >=2 Steps From Baseline in the DRSS Score at Week 24 and Week 48 | 0 percentage of subjects |
| EYP-1901 2060 mcg (Week 48) | Percentage of Subjects Improved >=2 Steps From Baseline in the DRSS Score at Week 24 and Week 48 | 0 percentage of subjects |
| EYP-1901 3090 mcg (Week 24) | Percentage of Subjects Improved >=2 Steps From Baseline in the DRSS Score at Week 24 and Week 48 | 0 percentage of subjects |
| EYP-1901 3090 mcg (Week 48) | Percentage of Subjects Improved >=2 Steps From Baseline in the DRSS Score at Week 24 and Week 48 | 5.3 percentage of subjects |
95% CI: [-13.2, 26]
Secondary
Percentage of Subjects Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Weeks 24, 36 and 48
The vision threatening complications in the study eye due to diabetic retinopathy were indicated by the presence of Vitreous hemorrhage or the presence of Tractional retinal detachment reported on the Ocular Examination - Dilated Ophthalmoscopy CRF (PDR events), and Neovascularization for the Iris answered as Yes or Neovascularization for the Angle answered as Yes per the Ocular Examination - Slit Lamp Biomicroscopy CRF (anterior segment neovascularization (ASNV) events).
Time frame: Weeks 24, 36 and 48
Population: The FAS included all subjects who received at least 1 dose of study treatment (EYP-1901 or sham).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sham Injection | Percentage of Subjects Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Weeks 24, 36 and 48 | Week 36 | 3.8 percentage of subjects |
| Sham Injection | Percentage of Subjects Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Weeks 24, 36 and 48 | Week 24 | 0 percentage of subjects |
| Sham Injection | Percentage of Subjects Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Weeks 24, 36 and 48 | Week 48 | 3.8 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Weeks 24, 36 and 48 | Week 36 | 3.8 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Weeks 24, 36 and 48 | Week 24 | 3.8 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Weeks 24, 36 and 48 | Week 48 | 3.8 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Weeks 24, 36 and 48 | Week 24 | 0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Weeks 24, 36 and 48 | Week 48 | 0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Weeks 24, 36 and 48 | Week 36 | 0 percentage of subjects |
Secondary
Percentage of Subjects Who Developed Center Involved-Diabetic Macular Edema (CI-DME) at Weeks 24, 36 and 48
The CI-DME in the study eye occurred when a treatment emergent adverse event (TEAE) with a mapped preferred term of 'Cystoid macular oedema', 'Diabetic retinal oedema', or 'Macular oedema' occurred in the study eye, in combination with the temporally closest centrally read custom algorithm CST measurement being greater than or equal to 320 microns.
Time frame: Weeks 24, 36 and 48
Population: The FAS included all subjects who received at least 1 dose of study treatment (EYP-1901 or sham).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sham Injection | Percentage of Subjects Who Developed Center Involved-Diabetic Macular Edema (CI-DME) at Weeks 24, 36 and 48 | Week 48 | 3.8 percentage of subjects |
| Sham Injection | Percentage of Subjects Who Developed Center Involved-Diabetic Macular Edema (CI-DME) at Weeks 24, 36 and 48 | Week 24 | 0 percentage of subjects |
| Sham Injection | Percentage of Subjects Who Developed Center Involved-Diabetic Macular Edema (CI-DME) at Weeks 24, 36 and 48 | Week 36 | 0 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Who Developed Center Involved-Diabetic Macular Edema (CI-DME) at Weeks 24, 36 and 48 | Week 36 | 0 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Who Developed Center Involved-Diabetic Macular Edema (CI-DME) at Weeks 24, 36 and 48 | Week 48 | 0 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Who Developed Center Involved-Diabetic Macular Edema (CI-DME) at Weeks 24, 36 and 48 | Week 24 | 0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Who Developed Center Involved-Diabetic Macular Edema (CI-DME) at Weeks 24, 36 and 48 | Week 24 | 0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Who Developed Center Involved-Diabetic Macular Edema (CI-DME) at Weeks 24, 36 and 48 | Week 48 | 8.0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Who Developed Center Involved-Diabetic Macular Edema (CI-DME) at Weeks 24, 36 and 48 | Week 36 | 4.0 percentage of subjects |
Secondary
Percentage of Subjects Who Received Anti-Vascular Endothelial Growth Factor (VEGF) or Additional Standard of Care Intervention Due to Ocular Diabetic Complications at Weeks 24, 36 and 48
Percentage of subjects who received anti-VEGF or additional standard of care intervention due to ocular diabetic complications in the study eye are reported. Anti-VEGF use was identified in reported concomitant medication data.
Time frame: Weeks 24, 36 and 48
Population: The FAS included all subjects who received at least 1 dose of study treatment (EYP-1901 or sham).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sham Injection | Percentage of Subjects Who Received Anti-Vascular Endothelial Growth Factor (VEGF) or Additional Standard of Care Intervention Due to Ocular Diabetic Complications at Weeks 24, 36 and 48 | Week 36 | 7.7 percentage of subjects |
| Sham Injection | Percentage of Subjects Who Received Anti-Vascular Endothelial Growth Factor (VEGF) or Additional Standard of Care Intervention Due to Ocular Diabetic Complications at Weeks 24, 36 and 48 | Week 24 | 7.7 percentage of subjects |
| Sham Injection | Percentage of Subjects Who Received Anti-Vascular Endothelial Growth Factor (VEGF) or Additional Standard of Care Intervention Due to Ocular Diabetic Complications at Weeks 24, 36 and 48 | Week 48 | 7.7 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Who Received Anti-Vascular Endothelial Growth Factor (VEGF) or Additional Standard of Care Intervention Due to Ocular Diabetic Complications at Weeks 24, 36 and 48 | Week 36 | 7.7 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Who Received Anti-Vascular Endothelial Growth Factor (VEGF) or Additional Standard of Care Intervention Due to Ocular Diabetic Complications at Weeks 24, 36 and 48 | Week 24 | 7.7 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Who Received Anti-Vascular Endothelial Growth Factor (VEGF) or Additional Standard of Care Intervention Due to Ocular Diabetic Complications at Weeks 24, 36 and 48 | Week 48 | 7.7 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Who Received Anti-Vascular Endothelial Growth Factor (VEGF) or Additional Standard of Care Intervention Due to Ocular Diabetic Complications at Weeks 24, 36 and 48 | Week 24 | 4.0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Who Received Anti-Vascular Endothelial Growth Factor (VEGF) or Additional Standard of Care Intervention Due to Ocular Diabetic Complications at Weeks 24, 36 and 48 | Week 48 | 12.0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Who Received Anti-Vascular Endothelial Growth Factor (VEGF) or Additional Standard of Care Intervention Due to Ocular Diabetic Complications at Weeks 24, 36 and 48 | Week 36 | 8.0 percentage of subjects |
Secondary
Percentage of Subjects Who Received PRP at Weeks 24, 36 and 48
Percentage of subjects who received PRP in the study eye, inclusive of subjects undergoing vitrectomy with endo-laser are reported.
Time frame: Weeks 24, 36 and 48
Population: The FAS included all subjects who received at least 1 dose of study treatment (EYP-1901 or sham).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sham Injection | Percentage of Subjects Who Received PRP at Weeks 24, 36 and 48 | Week 36 | 0 percentage of subjects |
| Sham Injection | Percentage of Subjects Who Received PRP at Weeks 24, 36 and 48 | Week 24 | 0 percentage of subjects |
| Sham Injection | Percentage of Subjects Who Received PRP at Weeks 24, 36 and 48 | Week 48 | 0 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Who Received PRP at Weeks 24, 36 and 48 | Week 36 | 3.8 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Who Received PRP at Weeks 24, 36 and 48 | Week 24 | 3.8 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Who Received PRP at Weeks 24, 36 and 48 | Week 48 | 3.8 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Who Received PRP at Weeks 24, 36 and 48 | Week 24 | 0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Who Received PRP at Weeks 24, 36 and 48 | Week 48 | 0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Who Received PRP at Weeks 24, 36 and 48 | Week 36 | 0 percentage of subjects |
Secondary
Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48
The DRSS used to describe overall retinopathy severity as well as the change in severity over time in the study eye. Severity ranges from level 10 (diabetic retinopathy absent) to level 85 (advanced PDR: posterior fundus obscured, or center of macula detached). Here, DRSS describes severity level 47 (moderately severe NPDR) and level 53 (severe NPDR) at Weeks 24, 36 and 48 from baseline.
Time frame: Baseline (Day 1) and Weeks 24, 36 and 48
Population: The FAS included all subjects who received at least 1 dose of study treatment (EYP-1901 or sham). Only subjects analyzed at specific timepoints are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sham Injection | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step worsening in DRSS: Week 24 | 0 percentage of subjects |
| Sham Injection | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step worsening in DRSS: Week 36 | 10.0 percentage of subjects |
| Sham Injection | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step worsening in DRSS: Week 48 | 0 percentage of subjects |
| Sham Injection | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step worsening in DRSS: Week 24 | 0 percentage of subjects |
| Sham Injection | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step worsening in DRSS: Week 36 | 5.0 percentage of subjects |
| Sham Injection | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step worsening in DRSS: Week 48 | 0 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step worsening in DRSS: Week 48 | 0 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step worsening in DRSS: Week 24 | 6.3 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step worsening in DRSS: Week 24 | 0 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step worsening in DRSS: Week 36 | 0 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step worsening in DRSS: Week 36 | 5.0 percentage of subjects |
| EYP-1901 2060 mcg | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step worsening in DRSS: Week 48 | 5.0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step worsening in DRSS: Week 36 | 0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step worsening in DRSS: Week 48 | 0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step worsening in DRSS: Week 48 | 0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step worsening in DRSS: Week 24 | 0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=2-step worsening in DRSS: Week 24 | 0 percentage of subjects |
| EYP-1901 3090 mcg | Percentage of Subjects Worsened >=2 Steps and >=3 Steps From Baseline in DRSS Score at Weeks 24, 36 and 48 | >=3-step worsening in DRSS: Week 36 | 0 percentage of subjects |
Secondary
Plasma Concentration of EYP-1901 and X-297 at Weeks 24, 36 and 48
Blood samples were collected at the specific visits for the Pharmacokinetic (PK) analysis of EYP-1901 and its main metabolite concentrations.
Time frame: Weeks 24, 36 and 48
Population: The PK analysis set included all subjects in the Safety set for whom at least 1 evaluable PK sample was available. Only subjects analysis at specific timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham Injection | Plasma Concentration of EYP-1901 and X-297 at Weeks 24, 36 and 48 | X-297: Week 24 | 0.000 mcg/mL | Standard Deviation 0 |
| Sham Injection | Plasma Concentration of EYP-1901 and X-297 at Weeks 24, 36 and 48 | EYP-1901: Week 24 | 11.852 mcg/mL | Standard Deviation 5.618 |
| Sham Injection | Plasma Concentration of EYP-1901 and X-297 at Weeks 24, 36 and 48 | X-297: Week 36 | 0.999 mcg/mL | Standard Deviation 4.7917 |
| Sham Injection | Plasma Concentration of EYP-1901 and X-297 at Weeks 24, 36 and 48 | EYP-1901: Week 48 | 6.698 mcg/mL | Standard Deviation 3.7642 |
| Sham Injection | Plasma Concentration of EYP-1901 and X-297 at Weeks 24, 36 and 48 | X-297: Week 48 | 0.000 mcg/mL | Standard Deviation 0 |
| Sham Injection | Plasma Concentration of EYP-1901 and X-297 at Weeks 24, 36 and 48 | EYP-1901: Week 36 | 7.660 mcg/mL | Standard Deviation 4.8187 |
| EYP-1901 2060 mcg | Plasma Concentration of EYP-1901 and X-297 at Weeks 24, 36 and 48 | X-297: Week 48 | 0.657 mcg/mL | Standard Deviation 2.8631 |
| EYP-1901 2060 mcg | Plasma Concentration of EYP-1901 and X-297 at Weeks 24, 36 and 48 | EYP-1901: Week 36 | 9.708 mcg/mL | Standard Deviation 5.5782 |
| EYP-1901 2060 mcg | Plasma Concentration of EYP-1901 and X-297 at Weeks 24, 36 and 48 | EYP-1901: Week 48 | 8.194 mcg/mL | Standard Deviation 3.5894 |
| EYP-1901 2060 mcg | Plasma Concentration of EYP-1901 and X-297 at Weeks 24, 36 and 48 | X-297: Week 24 | 0.000 mcg/mL | Standard Deviation 0 |
| EYP-1901 2060 mcg | Plasma Concentration of EYP-1901 and X-297 at Weeks 24, 36 and 48 | X-297: Week 36 | 0.275 mcg/mL | Standard Deviation 1.2877 |
| EYP-1901 2060 mcg | Plasma Concentration of EYP-1901 and X-297 at Weeks 24, 36 and 48 | EYP-1901: Week 24 | 14.064 mcg/mL | Standard Deviation 5.0654 |
Secondary
Time to Develop Any Neovascular Vision Threatening Complication (PDR/ASNV) at Weeks 24, 36 and 48
Time to develop any PDR/ASNV was computed as the date of the first development of PDR/ASNV in the study eye minus the date of study treatment administration plus 1 day, divided by 7 days per week.
Time frame: Weeks 24, 36 and 48
Population: The FAS included all subjects who received at least 1 dose of study treatment (EYP-1901 or sham). Only subjects developed any PDR/ASNV at specific timepoint are analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Injection | Time to Develop Any Neovascular Vision Threatening Complication (PDR/ASNV) at Weeks 24, 36 and 48 | Week 36 | NA weeks |
| Sham Injection | Time to Develop Any Neovascular Vision Threatening Complication (PDR/ASNV) at Weeks 24, 36 and 48 | Week 48 | NA weeks |
| EYP-1901 2060 mcg | Time to Develop Any Neovascular Vision Threatening Complication (PDR/ASNV) at Weeks 24, 36 and 48 | Week 24 | NA weeks |
| EYP-1901 2060 mcg | Time to Develop Any Neovascular Vision Threatening Complication (PDR/ASNV) at Weeks 24, 36 and 48 | Week 36 | NA weeks |
| EYP-1901 2060 mcg | Time to Develop Any Neovascular Vision Threatening Complication (PDR/ASNV) at Weeks 24, 36 and 48 | Week 48 | NA weeks |
Secondary
Time to Develop CI-DME Through Weeks 24, 36 and 48
The occurrence of a CI-DME event in the study eye was identified via examination of centrally read custom algorithm CST data and adverse events.
Time frame: Weeks 24, 36 and 48
Population: The FAS included all subjects who received at least 1 dose of study treatment (EYP-1901 or sham). Only subjects developed CI-DME event at specific timepoint are analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Injection | Time to Develop CI-DME Through Weeks 24, 36 and 48 | Week 48 | NA weeks |
| EYP-1901 3090 mcg | Time to Develop CI-DME Through Weeks 24, 36 and 48 | Week 36 | NA weeks |
| EYP-1901 3090 mcg | Time to Develop CI-DME Through Weeks 24, 36 and 48 | Week 48 | NA weeks |
| Unknown | Time to Develop CI-DME Through Weeks 24, 36 and 48 | Week 24 | — weeks |