The TIME-2b Study: A Study of AKB-9778 (Razuprotafib), a Novel Tie 2 Activator, in Patients With Non-Proliferative Diabetic Retinopathy (NPDR) (TIME-2b)

Phase 2 Double-Masked, Placebo-Controlled Study to Assess the Safety and Efficacy of Subcutaneously Administered AKB-9778 (Razuprotafib)15mg Once Daily or 15mg Twice Daily for 12 Months in Patients With Moderate to Severe Non-Proliferative Diabetic Retinopathy

The purpose of this study is to evaluate the safety and efficacy of subcutaneously administered AKB-9778 15mg once daily or 15mg twice daily for 12 months in patients with moderate to severe non-proliferative diabetic retinopathy (NPDR).

Study Overview

• Status: Completed
• Conditions: Nonproliferative Diabetic Retinopathy
• Intervention / Treatment: Drug: AKB-9778; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85021
      • Arizona Retina and Vitreous Consultants
    • Phoenix, Arizona, United States, 85053
      • Retinal Research Institute
  • California
    • Arcadia, California, United States, 91007
      • Retina Institute of California
    • Bakersfield, California, United States, 93309
      • California Retina Consultants
    • Beverly Hills, California, United States, 90211
      • Retina Vitreous Associates Medical Group
    • Fullerton, California, United States, 92835
      • Retina Consultants of Orange County
    • Oceanside, California, United States, 92056
      • Ophthalmic Clinical Trials San Diego
    • Palo Alto, California, United States, 94303
      • Stanford
    • Santa Barbara, California, United States, 93103
      • California Retina Consultants
    • Santa Maria, California, United States, 93454
      • California Retina Consultants
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Retina Consultants of Southern Colorado
    • Golden, Colorado, United States, 80401
      • Colorado Retina Associates
  • Florida
    • Deerfield Beach, Florida, United States, 33064
      • Rand Eye Institute
    • Lakeland, Florida, United States, 33805
      • Center for Retina and Macular Disease
    • Pensacola, Florida, United States, 32503
      • Retina Specialty Institute
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
    • Marietta, Georgia, United States, 30060
      • Georgia Retina
  • Illinois
    • Oak Forest, Illinois, United States, 60452
      • University Retina
    • Oak Park, Illinois, United States, 60304
      • Illinois Retina Associates
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Midwest Eye Institute
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Wolfe Eye Clinic
  • Kansas
    • Wichita, Kansas, United States, 67226
      • Central Plains Eye MDs
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Retina Associates of Kentucky
  • Maryland
    • Baltimore, Maryland, United States, 212876
      • Johns Hopkins University School of Medicine
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Consultants PC
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Opthalmic Consultants of Boston
  • Michigan
    • Jackson, Michigan, United States, 49202
      • Specialty Eye Institute
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • New Jersey
    • Bloomfield, New Jersey, United States, 07003
      • Retina Center of New Jersey
    • Edison, New Jersey, United States, 08820
      • New Jersey Retina
    • Northfield, New Jersey, United States, 08225
      • Retinal and Ophthalmic Consultants P.C.
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Eye Associates of New Mexico
  • New York
    • Shirley, New York, United States, 11967
      • Island Retina
    • Syracuse, New York, United States, 13224
      • Retina Vitreous Surgeons of Central New York
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Retina Associates of Cleveland
    • Cincinnati, Ohio, United States, 45242
      • Cincinnati Eye Institute
    • Middleburg Heights, Ohio, United States, 44130
      • Retina Associates of Cleveland
    • Youngstown, Ohio, United States, 44505
      • Retina Associates of Cleveland
  • Oklahoma
    • Edmond, Oklahoma, United States, 73013
      • Retina Vitreous Center
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Mid-Atlantic Retina
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institute of Texas
    • Arlington, Texas, United States, 76012
      • Texas Retina Associates
    • Austin, Texas, United States, 78705
      • Austin Retina Associates
    • Austin, Texas, United States, 78705
      • Retina Research Center
    • Fort Worth, Texas, United States, 76104
      • Texas Retina Associates
    • Harlingen, Texas, United States, 78550
      • Valley Retina Institute
    • Houston, Texas, United States, 77030
      • Retina Consultants of Houston
    • Houston, Texas, United States, 77025
      • Retina and Vitreous of Texas
    • McAllen, Texas, United States, 78503
      • Valley Retina Institute
    • San Antonio, Texas, United States, 78240
      • Medical Center Ophthalmology Associates
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Houston
  • Washington
    • Spokane, Washington, United States, 99204
      • Spokane Eye Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Adults 18 through 80 years of age (inclusive)
• Subjects with moderate to very severe NPDR (ETDRS Level 43 - 53 inclusive)
• No evidence of central involved diabetic macular edema
• ETDRS best-corrected visual acuity letter score ≥ 70 (Snellen 20/40 or better)

Key Exclusion Criteria:

• Ocular disease other than DR that may cause substantial reduction in visual acuity, including iris neovascularization, retinal detachment, visually significant epiretinal membrane, vitreous hemorrhage or fibrosis, ocular inflammation (uveitis), other retinal inflammatory or infectious diseases
• Evidence of neovascularization on clinical examination or imaging
• Hemoglobin A1C (HbA1C) ≥ 12.0% at Screening
• Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AKB-9778 15mg Daily; AKB-9778 15 mg (QD); To maintain masking, subjects will receive BID dosing with masked study medication administered as one dose of active and one dose of matching placebo	Drug: AKB-9778; Subcutaneous AKB-9778 15mg; Drug: Placebo; Subcutaneous Placebo
Experimental: AKB-9778 15mg Twice Daily; AKB-9778 15 mg (BID)	Drug: AKB-9778; Subcutaneous AKB-9778 15mg
Placebo Comparator: Placebo Twice Daily; Placebo Group: SC Phosphate-Buffered-Saline (PBS) (BID)	Drug: Placebo; Subcutaneous Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With an Improvement in Study Eye Severity of Diabetic Retinopathy (DR) (ETDRS DR Severity Score or DRSS) of ≥ 2 Steps	Change from baseline to Week 48 in Diabetic Retinopathy Severity Scale Score in Study Eye by visit in the modified intent-to-treat population. ETDRS DR severity levels 10-85; ETDRS Steps 1-12	Baseline to Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary of Subjects With a Worsening in the Study Eye DRSS of ≥ 2 Steps at Week 48	Worsening of Diabetic Retinopathy Severity Score (DRSS) severity of ≥ 2 steps in study eyes at Week 48 (compared to placebo group) Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR	Baseline to Week 48
Mean Change From Baseline in DRSS in the Study Eye at Week 48	Mean change from baseline in Diabetic Retinopathy Severity Score (DRSS) in the study eye at week 48. Note: Observed values at Week 48 instead of change from baseline values at Week 48 were analyzed Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR	Week 48
Summary of Subjects With an Improvement or Worsening in the Study Eye DRSS of ≥ 3 Steps at Week 48.	Summary of subjects with an improvement or worsening in the study eye Diabetic Retinopathy Severity Score (DRSS) of ≥ 3 steps at Week 48 (compared to placebo) Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR	Baseline to Week 48
Subjects With Criterion Step Improvement in DRSS at Week 48/EOT (>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and >=3 Steps Improvement on the Person Scale for Patients With Qualified Fellow Eyes)	Subjects with Criterion Step Improvement in Diabetic Retinopathy Severity Score (DRSS) at Week 48/EOT (>=2 Steps Improvement in the Study Eye for Patients with Non-qualified Fellow Eye and >=3 Steps Improvement on the Person Scale for Patients with Qualified Fellow Eyes). Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR	Treatment Period - 12 months (48 weeks)
Subjects With Criterion Step Improvement in DRSS at Week 48/EOT (>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and >=3 Steps Improvement on the Binocular Scale for Patients With Qualified Fellow Eyes)	Subjects With Criterion Step Improvement in Diabetic Retinopathy Severity Score (DRSS) at Week 48/EOT (>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and >=3 Steps Improvement on the Binocular Scale for Patients With Qualified Fellow Eyes). Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR	Treatment Period - 12 months (48 weeks)
Summary of Patients Developing Center-involved DME or PDR or PDR-related Outcomes During Treatment Period Based on Clinical Data.	Summary of patients developing center-involved Diabetic Macular Edema (DME) or Proliferative Diabetic Retinopathy (PDR) or PDR-related outcomes during treatment period based on Clinical Data. Based on either clinical data or central image reading center evaluation.	Treatment Period - 12 months (48 weeks)
Summary of Subjects Developing Center-involved DME or PDR or Worsening of >=2 Steps DRSS at Week 48 Based on Central Image Reading Center Evaluation	Summary of Subjects Developing Center-involved Diabetic Macular Edema (DME) or Proliferative Diabetic Retinopathy (PDR) or Worsening of >=2 Steps Diabetic Retinopathy Severity Scale (DRSS) at Week 48 Based on Central Image Reading Center Evaluation - Study Eyes Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR	Treatment Period - 12 months (48 weeks)

Collaborators and Investigators

• Sponsor: EyePoint Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2017
• Primary Completion (Actual): January 9, 2019
• Study Completion (Actual): February 9, 2019

Study Registration Dates

• First Submitted: June 22, 2017
• First Submitted That Met QC Criteria: June 22, 2017
• First Posted (Actual): June 23, 2017

Study Record Updates

• Last Update Posted (Actual): June 27, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Diseases; Diabetic Retinopathy
• Other Study ID Numbers: AKB-9778-CI-5001

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