Study of EYP-1901 in Patients With Nonproliferative Diabetic Retinopathy (NPDR)

A Phase 2, Multicenter, Prospective, Double-masked, Parallel Study of EYP-1901, a Tyrosine Kinase Inhibitor (TKI), Compared to Sham for the Improvement of Moderately Severe to Severe Nonproliferative Diabetic Retinopathy (NPDR)

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.

Study Overview

• Status: Completed
• Conditions: Nonproliferative Diabetic Retinopathy
• Intervention / Treatment: Drug: EYP-1901; Other: Sham IVT

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.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85020
      • EyePoint Investigative Site
  • California
    • Huntington Beach, California, United States, 92647
      • EyePoint Investigative Site
    • Oxnard, California, United States, 93036
      • EyePoint Investigative Site
    • Palm Desert, California, United States, 92211
      • EyePoint Investigative Site
    • Pasadena, California, United States, 90041
      • EyePoint Investigative Site
    • Poway, California, United States, 92064
      • EyePoint Investigative Site
    • Sacramento, California, United States, 95825
      • EyePoint Investigative Site
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • EyePoint Investigative Site
  • Florida
    • Clearwater, Florida, United States, 33761
      • EyePoint Investigative Site
    • Melbourne, Florida, United States, 32901
      • EyePoint Investigative Site
    • Miami, Florida, United States, 33143
      • EyePoint Investigative Site
    • Winter Haven, Florida, United States, 33880
      • EyePoint Investigative Site
  • Illinois
    • Lemont, Illinois, United States, 60439
      • EyePoint Investigative Site
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • EyePoint Investigative Site
  • Kansas
    • Lenexa, Kansas, United States, 66215
      • EyePoint Investigative Site
  • Maryland
    • Baltimore, Maryland, United States, 21209
      • EyePoint Investigative Site
    • Hagerstown, Maryland, United States, 21740
      • EyePoint Investigative Site
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • EyePoint Investigative Site
  • Nevada
    • Reno, Nevada, United States, 89502
      • EyePoint Investigative Site
  • New Jersey
    • Bloomfield, New Jersey, United States, 07003
      • EyePoint Investigative Site
    • Toms River, New Jersey, United States, 08755
      • EyePoint Investigative Site
  • New York
    • Great Neck, New York, United States, 11021
      • EyePoint Investigative Site
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16501
      • EyePoint Investigative Site
  • South Carolina
    • Florence, South Carolina, United States, 29501
      • EyePoint Investigative Site
    • Ladson, South Carolina, United States, 29456
      • EyePoint Investigative Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • EyePoint Investigative Site
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • EyePoint Investigative Site
  • Texas
    • Abilene, Texas, United States, 79606
      • EyePoint Investigative Site
    • Austin, Texas, United States, 78705
      • EyePoint Investigative Site
    • Houston, Texas, United States, 78240
      • EyePoint Investigative Site
    • McAllen, Texas, United States, 78503
      • EyePoint Investigative Site
    • Plano, Texas, United States, 75075
      • EyePoint Investigative Site
    • San Antonio, Texas, United States, 78247
      • EyePoint Investigative Site
    • The Woodlands, Texas, United States, 77384
      • EyePoint Investigative Site
  • Virginia
    • Lynchburg, Virginia, United States, 24502
      • EyePoint Investigative Site
  • Washington
    • Bellevue, Washington, United States, 98004
      • EyePoint Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EYP-1901 2060 ug; EYP-1901 2060 ug; single injection	Drug: EYP-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.; Other Names: Vorolanib
Experimental: EYP-1901 3090 ug; EYP-1901 3090 ug; single injection	Drug: EYP-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.; Other Names: Vorolanib
Sham Comparator: Sham IVT; Sham IVT; single injection	Other: Sham IVT; Sham injections will be used to maintain masking of investigational EYP-1901 therapy for study subjects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline (Day 1) and Week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline (Day 1) and Weeks 24, 36 and 48
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.	Baseline (Day 1) and Weeks 24, 36 and 48
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).	Weeks 24, 36 and 48
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.	Weeks 24, 36 and 48
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.	Weeks 24, 36 and 48
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.	Weeks 24, 36 and 48
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.	Weeks 24, 36 and 48
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.	Weeks 24, 36 and 48
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.	Weeks 24, 36 and 48
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.	Weeks 24, 36 and 48
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.	TEAEs were collected from the study drug administration (Day 1) up to end of the study, approximately 48 weeks.
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.	Baseline (Day 1), Week 24, and Week 48

Collaborators and Investigators

• Sponsor: EyePoint Pharmaceuticals, Inc.
• Investigators: Study Director: Ramiro Ribeiro, MD, PhD, EyePoint Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2022
• Primary Completion (Actual): February 12, 2024
• Study Completion (Actual): May 6, 2024

Study Registration Dates

• First Submitted: May 10, 2022
• First Submitted That Met QC Criteria: May 16, 2022
• First Posted (Actual): May 20, 2022

Study Record Updates

• Last Update Posted (Estimated): August 15, 2025
• Last Update Submitted That Met QC Criteria: August 13, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: NPDR; EYP-1901; EyePoint
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Diabetes Mellitus; Eye Diseases; Diabetic Angiopathies; Diabetes Complications; Retinal Diseases; Diabetic Retinopathy; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Vorolanib
• Other Study ID Numbers: EYP-1901-204

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No