The TIME-2b Study: A Study of AKB-9778 (Razuprotafib), a Novel Tie 2 Activator, in Patients With Non-Proliferative Diabetic Retinopathy (NPDR)
- Conditions
- Nonproliferative Diabetic Retinopathy
- Interventions
- Drug: AKB-9778Drug: Placebo
- Registration Number
- NCT03197870
- Lead Sponsor
- EyePoint Pharmaceuticals, Inc.
- Brief 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 167
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AKB-9778 15mg Daily AKB-9778 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 AKB-9778 15mg Twice Daily AKB-9778 AKB-9778 15 mg (BID) AKB-9778 15mg Daily Placebo 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 Placebo Twice Daily Placebo Placebo Group: SC Phosphate-Buffered-Saline (PBS) (BID)
- Primary Outcome Measures
Name Time Method Percentage of Subjects With an Improvement in Study Eye Severity of Diabetic Retinopathy (DR) (ETDRS DR Severity Score or DRSS) of ≥ 2 Steps Baseline to Week 48 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
- Secondary Outcome Measures
Name Time Method Mean Change From Baseline in DRSS in the Study Eye at Week 48 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 PDRSubjects 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) Treatment Period - 12 months (48 weeks) 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 PDRSummary of Patients Developing Center-involved DME or PDR or PDR-related Outcomes During Treatment Period Based on Clinical Data. Treatment Period - 12 months (48 weeks) 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.
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 Treatment Period - 12 months (48 weeks) 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 PDRSummary of Subjects With a Worsening in the Study Eye DRSS of ≥ 2 Steps at Week 48 Baseline to 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 PDRSummary of Subjects With an Improvement or Worsening in the Study Eye DRSS of ≥ 3 Steps at Week 48. Baseline to 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 PDRSubjects 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) Treatment Period - 12 months (48 weeks) 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
Trial Locations
- Locations (46)
Retina Consultants of Orange County
🇺🇸Fullerton, California, United States
Southeast Retina Center
🇺🇸Augusta, Georgia, United States
Georgia Retina
🇺🇸Marietta, Georgia, United States
Sierra Eye Associates
🇺🇸Reno, Nevada, United States
Retina Associates of Cleveland
🇺🇸Youngstown, Ohio, United States
Retina and Vitreous of Texas
🇺🇸Houston, Texas, United States
Midwest Eye Institute
🇺🇸Indianapolis, Indiana, United States
Cincinnati Eye Institute
🇺🇸Cincinnati, Ohio, United States
Colorado Retina Associates
🇺🇸Golden, Colorado, United States
Retina Consultants of Southern Colorado
🇺🇸Colorado Springs, Colorado, United States
Rand Eye Institute
🇺🇸Deerfield Beach, Florida, United States
Johns Hopkins University School of Medicine
🇺🇸Baltimore, Maryland, United States
Cumberland Valley Retina Consultants PC
🇺🇸Hagerstown, Maryland, United States
Center for Retina and Macular Disease
🇺🇸Lakeland, Florida, United States
Retina Specialty Institute
🇺🇸Pensacola, Florida, United States
Specialty Eye Institute
🇺🇸Jackson, Michigan, United States
Illinois Retina Associates
🇺🇸Oak Park, Illinois, United States
Retina Center of New Jersey
🇺🇸Bloomfield, New Jersey, United States
Opthalmic Consultants of Boston
🇺🇸Boston, Massachusetts, United States
Arizona Retina and Vitreous Consultants
🇺🇸Phoenix, Arizona, United States
Tennessee Retina
🇺🇸Nashville, Tennessee, United States
Retinal Research Institute
🇺🇸Phoenix, Arizona, United States
Medical Center Ophthalmology Associates
🇺🇸San Antonio, Texas, United States
Retina Institute of California
🇺🇸Arcadia, California, United States
California Retina Consultants
🇺🇸Santa Maria, California, United States
Retina Vitreous Associates Medical Group
🇺🇸Beverly Hills, California, United States
Ophthalmic Clinical Trials San Diego
🇺🇸Oceanside, California, United States
Stanford
🇺🇸Palo Alto, California, United States
University Retina
🇺🇸Oak Forest, Illinois, United States
Wolfe Eye Clinic
🇺🇸West Des Moines, Iowa, United States
Retina Associates of Kentucky
🇺🇸Lexington, Kentucky, United States
New Jersey Retina
🇺🇸Edison, New Jersey, United States
Retinal and Ophthalmic Consultants P.C.
🇺🇸Northfield, New Jersey, United States
Eye Associates of New Mexico
🇺🇸Albuquerque, New Mexico, United States
Island Retina
🇺🇸Shirley, New York, United States
Retina Vitreous Surgeons of Central New York
🇺🇸Syracuse, New York, United States
Retina Vitreous Center
🇺🇸Edmond, Oklahoma, United States
Mid-Atlantic Retina
🇺🇸Bethlehem, Pennsylvania, United States
Retina Research Institute of Texas
🇺🇸Abilene, Texas, United States
Retina Research Center
🇺🇸Austin, Texas, United States
Texas Retina Associates
🇺🇸Fort Worth, Texas, United States
Austin Retina Associates
🇺🇸Austin, Texas, United States
Retina Consultants of Houston
🇺🇸The Woodlands, Texas, United States
Spokane Eye Clinical Research
🇺🇸Spokane, Washington, United States
Valley Retina Institute
🇺🇸McAllen, Texas, United States
Central Plains Eye MDs
🇺🇸Wichita, Kansas, United States