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NCT Number: NCT03197870

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

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).

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Key information

Conditions

Nonproliferative Diabetic Retinopathy

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Arizona Retina and Vitreous Consultants, Phoenix, Arizona, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

AKB-9778

Drug

Subcutaneous AKB-9778 15mg

Placebo

Drug

Subcutaneous Placebo

Primary outcomes

  1. Percentage of Subjects With an Improvement in Study Eye Severity of Diabetic Retinopathy (DR) (ETDRS DR Severity Score or DRSS) of ≥ 2 Steps

    Time frame: 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 outcomes

  1. Summary of Subjects With a Worsening in the Study Eye DRSS of ≥ 2 Steps at Week 48

    Time frame: 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 PDR

  2. Mean Change From Baseline in DRSS in the Study Eye at Week 48

    Time frame: 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

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

    Time frame: 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 PDR

  4. 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)

    Time frame: 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 PDR

  5. 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)

    Time frame: 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

  6. Summary of Patients Developing Center-involved DME or PDR or PDR-related Outcomes During Treatment Period Based on Clinical Data.

    Time frame: 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.

  7. 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

    Time frame: 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 PDR

Sponsors and collaborators

Lead sponsor

EyePoint Pharmaceuticals, Inc.

Industry

Registry information

Official study 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

Acronym: TIME-2b

Important dates

Study start
2017
Primary completion
2019
Study completion
2019
First posted
Jun 23, 2017
Registry last updated
Jun 27, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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