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NCT04964089: DAYLIGHT

A 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)

Completed Phase 3 Results posted Last updated 3 July 2024
What this trial tests

Phase 3 trial testing KSI-301 in Wet Age-related Macular Degeneration in 557 participants. Completed in 6 April 2023.

Timeline
23 June 2021
Primary endpoint
28 March 2023
6 April 2023

Quick facts

Lead sponsorKodiak Sciences Inc
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment557
Start date23 June 2021
Primary completion28 March 2023
Estimated completion6 April 2023
Sites66 locations across Puerto Rico, United States

Drugs / interventions tested

Conditions studied

Sponsor

Kodiak Sciences Inc — full company profile →

Who can join

50 and older, any sex, with Wet Age-related Macular Degeneration. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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. Primary · 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.

GroupValue95% CI
KSI-301 (Treatment Group A)2.5± 0.78
Aflibercept (Treatment Group B)4.6± 0.76
Mean Change in Best Corrected Visual Acuity (BCVA) by Visit Over Time Secondary · 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.

Week 2
GroupValue95% CI
KSI-301 (Treatment Group A)2.8± 6.48
Aflibercept (Treatment Group B)2.9± 7.12
Week 4
GroupValue95% CI
KSI-301 (Treatment Group A)3.4± 7.05
Aflibercept (Treatment Group B)4.2± 7.29
Week 8
GroupValue95% CI
KSI-301 (Treatment Group A)3.7± 8.52
Aflibercept (Treatment Group B)5.1± 7.86
Week 12
GroupValue95% CI
KSI-301 (Treatment Group A)3.8± 8.83
Aflibercept (Treatment Group B)5.4± 7.90
Week 16
GroupValue95% CI
KSI-301 (Treatment Group A)3.6± 9.09
Aflibercept (Treatment Group B)4.9± 8.54
Week 20
GroupValue95% CI
KSI-301 (Treatment Group A)3.9± 9.60
Aflibercept (Treatment Group B)5.7± 8.97
Week 24
GroupValue95% CI
KSI-301 (Treatment Group A)4.5± 9.29
Aflibercept (Treatment Group B)6.0± 9.45
Week 28
GroupValue95% CI
KSI-301 (Treatment Group A)4.5± 9.75
Aflibercept (Treatment Group B)6.1± 9.49
Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Secondary · Day 1 to Week 48

Categorical improvements in Best Corrected Visual Acuity (BCVA) of clinically relevant BCVA measurements corresponding to 1, 2 and 3 lines of the ETDRS vision testing chart

Gain ≥5 ETDRS Letters at Week 2
GroupValue95% CI
KSI-301 (Treatment Group A)100
Aflibercept (Treatment Group B)96
Gain ≥5 ETDRS Letters at Week 4
GroupValue95% CI
KSI-301 (Treatment Group A)110
Aflibercept (Treatment Group B)129
Gain ≥5 ETDRS Letters at Week 8
GroupValue95% CI
KSI-301 (Treatment Group A)119
Aflibercept (Treatment Group B)151
Gain ≥5 ETDRS Letters at Week 12
GroupValue95% CI
KSI-301 (Treatment Group A)124
Aflibercept (Treatment Group B)148
Gain ≥5 ETDRS Letters at Week 16
GroupValue95% CI
KSI-301 (Treatment Group A)119
Aflibercept (Treatment Group B)143
Gain ≥5 ETDRS Letters at Week 20
GroupValue95% CI
KSI-301 (Treatment Group A)121
Aflibercept (Treatment Group B)161
Gain ≥5 ETDRS Letters at Week 24
GroupValue95% CI
KSI-301 (Treatment Group A)130
Aflibercept (Treatment Group B)156
Gain ≥5 ETDRS Letters at Week 28
GroupValue95% CI
KSI-301 (Treatment Group A)122
Aflibercept (Treatment Group B)154
Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time Secondary · Day 1 to Week 48

Categorical worsening in Best Corrected Visual Acuity (BCVA) of clinically relevant BCVA measurements corresponding to 1, 2 and 3 lines of the ETDRS vision testing chart

Loss ≥ 5 ETDRS Letters at Week 2
GroupValue95% CI
KSI-301 (Treatment Group A)20
Aflibercept (Treatment Group B)28
Loss ≥ 5 ETDRS Letters at Week 4
GroupValue95% CI
KSI-301 (Treatment Group A)27
Aflibercept (Treatment Group B)19
Loss ≥ 5 ETDRS Letters at Week 8
GroupValue95% CI
KSI-301 (Treatment Group A)41
Aflibercept (Treatment Group B)22
Loss ≥ 5 ETDRS Letters at Week 12
GroupValue95% CI
KSI-301 (Treatment Group A)35
Aflibercept (Treatment Group B)24
Loss ≥ 5 ETDRS Letters at Week 16
GroupValue95% CI
KSI-301 (Treatment Group A)35
Aflibercept (Treatment Group B)31
Loss ≥ 5 ETDRS Letters at Week 20
GroupValue95% CI
KSI-301 (Treatment Group A)35
Aflibercept (Treatment Group B)27
Loss ≥ 5 ETDRS Letters at Week 24
GroupValue95% CI
KSI-301 (Treatment Group A)34
Aflibercept (Treatment Group B)31
Loss ≥ 5 ETDRS Letters at Week 28
GroupValue95% CI
KSI-301 (Treatment Group A)38
Aflibercept (Treatment Group B)31
Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) Secondary · 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.

Snellen Equivalent of 20/40 or Better at Baseline
GroupValue95% CI
KSI-301 (Treatment Group A)122
Aflibercept (Treatment Group B)129
Snellen Equivalent of 20/40 or Better at Week 2
GroupValue95% CI
KSI-301 (Treatment Group A)148
Aflibercept (Treatment Group B)152
Snellen Equivalent of 20/40 or Better at Week 4
GroupValue95% CI
KSI-301 (Treatment Group A)156
Aflibercept (Treatment Group B)165
Snellen Equivalent of 20/40 or Better at Week 8
GroupValue95% CI
KSI-301 (Treatment Group A)156
Aflibercept (Treatment Group B)165
Snellen Equivalent of 20/40 or Better at Week 12
GroupValue95% CI
KSI-301 (Treatment Group A)148
Aflibercept (Treatment Group B)171
Snellen Equivalent of 20/40 or Better at Week 16
GroupValue95% CI
KSI-301 (Treatment Group A)149
Aflibercept (Treatment Group B)172
Snellen Equivalent of 20/40 or Better at Week 20
GroupValue95% CI
KSI-301 (Treatment Group A)151
Aflibercept (Treatment Group B)179
Snellen Equivalent of 20/40 or Better at Week 24
GroupValue95% CI
KSI-301 (Treatment Group A)158
Aflibercept (Treatment Group B)183
Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters) Secondary · 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.

Snellen Equivalent of 20/200 or Worse at Baseline
GroupValue95% CI
KSI-301 (Treatment Group A)17
Aflibercept (Treatment Group B)15
Snellen Equivalent of 20/200 or Worse at Week 2
GroupValue95% CI
KSI-301 (Treatment Group A)11
Aflibercept (Treatment Group B)12
Snellen Equivalent of 20/200 or Worse at Week 4
GroupValue95% CI
KSI-301 (Treatment Group A)10
Aflibercept (Treatment Group B)14
Snellen Equivalent of 20/200 or Worse at Week 8
GroupValue95% CI
KSI-301 (Treatment Group A)11
Aflibercept (Treatment Group B)13
Snellen Equivalent of 20/200 or Worse at Week 12
GroupValue95% CI
KSI-301 (Treatment Group A)11
Aflibercept (Treatment Group B)12
Snellen Equivalent of 20/200 or Worse at Week 16
GroupValue95% CI
KSI-301 (Treatment Group A)11
Aflibercept (Treatment Group B)10
Snellen Equivalent of 20/200 or Worse at Week 20
GroupValue95% CI
KSI-301 (Treatment Group A)13
Aflibercept (Treatment Group B)13
Snellen Equivalent of 20/200 or Worse at Week 24
GroupValue95% CI
KSI-301 (Treatment Group A)11
Aflibercept (Treatment Group B)13
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over Time Secondary · Day 1 to Week 48

Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) as assessed by a central reading center.

Week 2
GroupValue95% CI
KSI-301 (Treatment Group A)-72.1± 83.74
Aflibercept (Treatment Group B)-99.9± 93.75
Week 4
GroupValue95% CI
KSI-301 (Treatment Group A)-74.9± 98.33
Aflibercept (Treatment Group B)-109.4± 100.87
Week 8
GroupValue95% CI
KSI-301 (Treatment Group A)-89.1± 121.13
Aflibercept (Treatment Group B)-122.2± 109.58
Week 12
GroupValue95% CI
KSI-301 (Treatment Group A)-97.1± 118.62
Aflibercept (Treatment Group B)-126.3± 111.55
Week 16
GroupValue95% CI
KSI-301 (Treatment Group A)-107.2± 110.02
Aflibercept (Treatment Group B)-99.2± 110.47
Week 20
GroupValue95% CI
KSI-301 (Treatment Group A)-111± 112.97
Aflibercept (Treatment Group B)-125.5± 117.39
Week 24
GroupValue95% CI
KSI-301 (Treatment Group A)-109.9± 112.82
Aflibercept (Treatment Group B)-101.8± 113.21
Week 28
GroupValue95% CI
KSI-301 (Treatment Group A)-114.6± 111.47
Aflibercept (Treatment Group B)-124.1± 111.51

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events (AEs) reported through Week 52 or Early Termination (ET). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

KSI-301 (Treatment Group A)
Serious: 39/276 (14%)
Deaths: 4/276
Aflibercept (Treatment Group B)
Serious: 39/281 (14%)
Deaths: 3/281

Serious adverse events (95 terms)

ReactionSystemKSI-301 (Treatment Group A)Aflibercept (Treatment Gro…
AnaemiaBlood and lymphatic system disorders
PneumoniaInfections and infestations
Atrial fibrillationCardiac disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Retinal detachment - Study eyeEye disorders
COVID-19 pneumoniaInfections and infestations
Clostridium difficile colitisInfections and infestations
SepsisInfections and infestations
Acute myocardial infarctionCardiac disorders
Coronary artery diseaseCardiac disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
Lung neoplasm malignantNeoplasms benign, malignant and unspecified (incl cysts and polyps)
AstheniaGeneral disorders
Pelvic fractureInjury, poisoning and procedural complications
Peripheral arterial occlusive diseaseVascular disorders
Periorbital cellulitis - Study eyeInfections and infestations
Viral infectionInfections and infestations
BronchitisInfections and infestations
COVID-19Infections and infestations
CellulitisInfections and infestations
Gastroenteritis viralInfections and infestations
Herpes zosterInfections and infestations
InfluenzaInfections and infestations
Respiratory syncytial virus infectionInfections and infestations
Respiratory tract infectionInfections and infestations
Other adverse events (7 terms — click to expand)

ReactionSystemKSI-301 (Treatment Group A)Aflibercept (Treatment Gro…
COVID-19Infections and infestations
Neovascular age-related macular degeneration - Fellow eyeEye disorders
Vitreous floaters - Study eyeEye disorders
Conjunctival haemorrhage - Study eyeEye disorders
HypertensionVascular disorders
Urinary tract infectionInfections and infestations
Intraocular pressure increased - Study eyeInvestigations

Most-reported serious reactions: Anaemia, Pneumonia, Atrial fibrillation, Respiratory failure, Retinal detachment - Study eye, COVID-19 pneumonia, Clostridium difficile colitis, Sepsis.

Data from ClinicalTrials.gov NCT04964089 adverse events section.

Sponsor's own description

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)

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Antibodies to watch in 2023.
    Kaplon H, Crescioli S, Chenoweth A, Visweswaraiah J, et al · · 2023 · cited 204× · PMID 36472472 · DOI 10.1080/19420862.2022.2153410
  2. Alternative Routes of Administration for Therapeutic Antibodies-State of the Art.
    Pitiot A, Heuzé-Vourc'h N, Sécher T. · · 2022 · cited 45× · PMID 36134952 · DOI 10.3390/antib11030056
  3. Delivery Systems in Ocular Retinopathies: The Promising Future of Intravitreal Hydrogels as Sustained-Release Scaffolds.
    Rafael D, Guerrero M, Marican A, Arango D, et al · · 2023 · cited 24× · PMID 37242726 · DOI 10.3390/pharmaceutics15051484
  4. Exploring new horizons in neovascular age-related macular degeneration: novel mechanisms of action and future therapeutic avenues.
    Shirian JD, Shukla P, Singh RP. · · 2025 · cited 16× · PMID 39379521 · DOI 10.1038/s41433-024-03373-x
  5. Advances in ophthalmic therapeutic delivery: A comprehensive overview of present and future directions.
    Torkashvand A, Izadian A, Hajrasouliha A. · · 2024 · cited 12× · PMID 38986847 · DOI 10.1016/j.survophthal.2024.07.002
  6. An Update on Strategies to Deliver Protein and Peptide Drugs to the Eye.
    Boddu SHS, Acharya D, Hala V, Jani H, et al · · 2023 · cited 12× · PMID 37810716 · DOI 10.1021/acsomega.3c02897
  7. Beyond the injection: delivery systems reshaping retinal disease management.
    Rowe LW, Akotoye C, Harris A, Ciulla TA. · · 2025 · cited 6× · PMID 40319468 · DOI 10.1080/14656566.2025.2496424
  8. Antibodies to watch in 2026.
    Crescioli S, Kaplon H, Chenoweth A, Hsu YS, et al · · 2026 · PMID 41560619 · DOI 10.1080/19420862.2026.2614669

Verify or expand the search:

Other trials of KSI-301

Trials testing the same drug.

Other recruiting trials for Wet Age-related Macular Degeneration

Currently open trials in the same condition.

Other Kodiak Sciences Inc trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04964089.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing