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

Phase 2CompletedNCT03197870

EyePoint Pharmaceuticals, Inc.167 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

167

Conditions

Nonproliferative Diabetic Retinopathy

Interventions

AKB-9778DRUG

Subcutaneous AKB-9778 15mg

PlaceboDRUG

Subcutaneous Placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (53)

Outcomes

Primary Outcomes

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

Time frame: Baseline to Week 48

Secondary Outcomes

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

Time frame: 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

Time frame: Week 48

Summary of Subjects With an Improvement or Worsening in the Study Eye DRSS of ≥ 3 Steps at Week 48.

Data from ClinicalTrials.gov

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Arizona Retina and Vitreous Consultants

Phoenix, Arizona, United States

Retinal Research Institute

Phoenix, Arizona, United States

Retina Institute of California

Arcadia, California, United States

California Retina Consultants

Bakersfield, California, United States

Retina Vitreous Associates Medical Group

Beverly Hills, California, United States

Retina Consultants of Orange County

Fullerton, California, United States

Ophthalmic Clinical Trials San Diego

Oceanside, California, United States

Stanford

Palo Alto, California, United States

California Retina Consultants

Santa Barbara, California, United States

California Retina Consultants

Santa Maria, California, United States

...and 43 more locations

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

Time frame: 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

Time frame: 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

Time frame: Treatment Period - 12 months (48 weeks)