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

Nonproliferative Diabetic Retinopathy Clinical Trial

— TIME-2b  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03197870
• Other study ID #: AKB-9778-CI-5001
• Status: Completed
• Phase: Phase 2
• Start date: June 9, 2017
• Est. completion date: February 9, 2019

Study information

• Verified date: June 2023
• Source: EyePoint Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 167
• Est. completion date: February 9, 2019
• Est. primary completion date: January 9, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Retinopathy
• Nonproliferative Diabetic Retinopathy
• Retinal Diseases

Intervention

Drug:
• AKB-9778
Subcutaneous AKB-9778 15mg
• Placebo
Subcutaneous Placebo

Locations

Country	Name	City	State
United States	Retina Research Institute of Texas	Abilene	Texas
United States	Eye Associates of New Mexico	Albuquerque	New Mexico
United States	Retina Institute of California	Arcadia	California
United States	Texas Retina Associates	Arlington	Texas
United States	Southeast Retina Center	Augusta	Georgia
United States	Austin Retina Associates	Austin	Texas
United States	Retina Research Center	Austin	Texas
United States	California Retina Consultants	Bakersfield	California
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Retina Associates of Cleveland	Beachwood	Ohio
United States	Mid-Atlantic Retina	Bethlehem	Pennsylvania
United States	Retina Vitreous Associates Medical Group	Beverly Hills	California
United States	Retina Center of New Jersey	Bloomfield	New Jersey
United States	Opthalmic Consultants of Boston	Boston	Massachusetts
United States	Cincinnati Eye Institute	Cincinnati	Ohio
United States	Retina Consultants of Southern Colorado	Colorado Springs	Colorado
United States	Rand Eye Institute	Deerfield Beach	Florida
United States	New Jersey Retina	Edison	New Jersey
United States	Retina Vitreous Center	Edmond	Oklahoma
United States	Texas Retina Associates	Fort Worth	Texas
United States	Retina Consultants of Orange County	Fullerton	California
United States	Colorado Retina Associates	Golden	Colorado
United States	Cumberland Valley Retina Consultants PC	Hagerstown	Maryland
United States	Valley Retina Institute	Harlingen	Texas
United States	Retina and Vitreous of Texas	Houston	Texas
United States	Retina Consultants of Houston	Houston	Texas
United States	Midwest Eye Institute	Indianapolis	Indiana
United States	Specialty Eye Institute	Jackson	Michigan
United States	Center for Retina and Macular Disease	Lakeland	Florida
United States	Retina Associates of Kentucky	Lexington	Kentucky
United States	Georgia Retina	Marietta	Georgia
United States	Valley Retina Institute	McAllen	Texas
United States	Retina Associates of Cleveland	Middleburg Heights	Ohio
United States	Tennessee Retina	Nashville	Tennessee
United States	Retinal and Ophthalmic Consultants P.C.	Northfield	New Jersey
United States	University Retina	Oak Forest	Illinois
United States	Illinois Retina Associates	Oak Park	Illinois
United States	Ophthalmic Clinical Trials San Diego	Oceanside	California
United States	Stanford	Palo Alto	California
United States	Retina Specialty Institute	Pensacola	Florida
United States	Arizona Retina and Vitreous Consultants	Phoenix	Arizona
United States	Retinal Research Institute	Phoenix	Arizona
United States	Sierra Eye Associates	Reno	Nevada
United States	Medical Center Ophthalmology Associates	San Antonio	Texas
United States	California Retina Consultants	Santa Barbara	California
United States	California Retina Consultants	Santa Maria	California
United States	Island Retina	Shirley	New York
United States	Spokane Eye Clinical Research	Spokane	Washington
United States	Retina Vitreous Surgeons of Central New York	Syracuse	New York
United States	Retina Consultants of Houston	The Woodlands	Texas
United States	Wolfe Eye Clinic	West Des Moines	Iowa
United States	Central Plains Eye MDs	Wichita	Kansas
United States	Retina Associates of Cleveland	Youngstown	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
EyePoint Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)