A Prospective, Randomized, Double-masked, Active Comparator-controlled, Multi-center, Two-arm, Phase 3 Study to Evaluate the Efficacy and Safety of Intravitreal KSI-301 Compared With Intravitreal Aflibercept in Participants With Neovascular (Wet) Age-related Macular Degeneration (wAMD)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Kodiak Sciences Inc
- Enrollment
- 557
- Locations
- 66
- Primary Endpoint
- Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to the Average of Non-missing BCVA Values of Weeks 40, 44 and 48.
Study Overview
Brief Summary
This Phase 3 study will evaluate the efficacy and safety of KSI-301 compared to aflibercept, in participants with neovascular (wet) age-related macular degeneration (wAMD)
Detailed Description
This is a Phase 3, prospective, randomized, double-masked, two-arm, multi-center non-inferiority study evaluating the efficacy and safety of repeated intravitreal dosing of KSI-301 5 mg in participants with visual impairment due to treatment-naïve neovascular (wet) age-related macular degeneration (wAMD)
The primary endpoint will be assessed as an average of Weeks 40, 44, and 48; additional secondary endpoints for efficacy will be assessed by visit over time
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description
For masking purposes, sham injections will be administered at every monthly visit if an active treatment is not administered. To preserve masking, two investigators are required for this study. The masked Investigator will be responsible for the examinations and safety assessments. The unmasked Investigator will perform the injections and post-treatment assessments.
Eligibility Criteria
- Ages
- 50 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Signed informed consent prior to participation in the study.
- •Treatment-naïve choroidal neovascularization (CNV) secondary to AMD.
- •BCVA ETDRS score between 83 and 25 letters, inclusive, in the Study Eye.
- •Decrease in vision in the Study Eye determined by the Investigator to be primarily the result of wAMD.
- •Other protocol-specified inclusion criteria may apply
Exclusion Criteria
- •BCVA of hand motion or worse in the non-Study Eye or non-physical presence of a non-Study Eye (i.e., monocular).
- •Active or suspected ocular or periocular infection or inflammation.
- •CNV secondary to other causes in the Study Eye.
- •Any history or evidence of a concurrent ocular condition present in the Study Eye, that in the opinion of the Investigator could require either medical or surgical intervention or affect macular edema or alter visual acuity during the study.
- •Uncontrolled glaucoma in the Study Eye.
- •Significant media opacities, including cataract, in the Study Eye that might interfere with visual acuity, assessment of safety, OCT or fundus photography.
- •Cataract in the Study Eye that in the judgment of the Investigator is expected to require surgical extraction within 12 months of screening.
- •Women who are pregnant or lactating or intending to become pregnant during the study.
- •Recent history (within the 6 months prior to screening) of myocardial infarction, stroke, transient ischemic attack, acute congestive heart failure or any acute coronary event.
- •History of a medical condition that, in the judgment of the Investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product.
- •Uncontrolled blood pressure defined as a systolic value ≥180 mmHg or diastolic value ≥100 mmHg while at rest.
- •Other protocol-specified exclusion criteria may apply
Arms & Interventions
KSI-301 (Treatment Group A)
Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44.
Intervention: KSI-301 (Drug)
Aflibercept (Treatment Group B)
Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered.
Intervention: Aflibercept (Drug)
Aflibercept (Treatment Group B)
Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered.
Intervention: Sham Procedure (Other)
Outcomes
Primary Outcomes
Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to the Average of Non-missing BCVA Values of Weeks 40, 44 and 48.
Time Frame: Day 1 to Week 48
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.
Secondary Outcomes
- Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters)(Day 1 to Week 48)
- Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time(Day 1 to Week 48)
- Mean Change in Best Corrected Visual Acuity (BCVA) by Visit Over Time(Day 1 to Week 48)
- Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters)(Day 1 to Week 48)
- Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time(Day 1 to Week 48)
- Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time(Day 1 to Week 48)