A Study to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Patients With Macular Edema Due to Retinal Vein Occlusion (RVO)

Phase 3

Completed

• Conditions: Macular Edema; Retinal Vein Occlusion
• Interventions: Drug: KSI-301; Drug: Aflibercept; Other: Sham Procedure

• Registration Number: NCT04592419
• Lead Sponsor: Kodiak Sciences Inc

Brief Summary

This Phase 3 study will evaluate the efficacy, durability, and safety of KSI-301 compared to aflibercept, in participants with macular edema due to treatment-naïve branch (BRVO) or central retinal vein occlusion (CRVO).

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 macular edema secondary to RVO (either branch or central type).

The primary endpoint will be assessed at Week 24; additional secondary endpoints for efficacy will be assessed at Week 24 and Week 48.

Study Timeline

• Study Start: 2020-09-25
• Study First Submitted: 2020-10-12
• Study First Submitted QC: 2020-10-16
• Study First Posted: 2020-10-19
• Primary Completion: 2022-06-10
• Study Completion: 2023-01-19
• Results First Submitted: 2024-04-04
• Results First Submitted QC: 2024-05-09
• Status Verified: 2024-06
• Results First Posted: 2024-06-06
• Last Update Submitted: 2024-06-14
• Last Update Posted: 2024-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 568

Inclusion Criteria

1. Signed informed consent prior to participation in the study.
2. Treatment-naïve macular edema of 6 months duration or less due to CRVO or BRVO. Participants with hemiretinal vein occlusion will be included as CRVO.
3. BCVA ETDRS letter score between 80 and 25 (20/25 to 20/320 Snellen equivalent), inclusive in the Study Eye.
4. CST of ≥ 320 microns on SD-OCT (Heidelberg Spectralis or equivalent on other OCT instruments) as determined by the Reading Center
5. Decrease in vision determined by the Investigator to be primarily the result of ME secondary to RVO.
6. Other protocol-specified inclusion criteria may apply.

Exclusion Criteria

1. Macular edema in the Study Eye for reasons other than RVO
2. Active iris or angle neovascularization, neovascular glaucoma, neovascularization of the optic disc, retinal neovascularization or vitreous hemorrhage in the Study Eye.
3. Uncontrolled glaucoma in the Study Eye.
4. Active retinal disease other than the condition under investigation in the Study Eye.
5. Any history or evidence of a concurrent ocular condition present, that in the opinion of the Investigator could require either medical or surgical intervention alter visual acuity during the study
6. Active or suspected ocular or periocular infection or inflammation
7. Any prior use of an approved or investigational treatment for macular edema secondary to RVO in the Study Eye (e.g. anti-VEGF, intraocular or periocular steroids, macular laser photocoagulation).
8. Women who are pregnant or lactating or intending to become pregnant during the study.
9. Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg or diastolic value ≥100 mmHg while at rest
10. 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.
11. 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.
12. Other protocol-specified exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aflibercept (Arm B)	Sham Procedure	Intravitreal injection of aflibercept (2 mg) once every 4 through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria.
KSI-301 (Arm A)	Sham Procedure	Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria.
KSI-301 (Arm A)	KSI-301	Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44. In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria.
Aflibercept (Arm B)	Aflibercept	Intravitreal injection of aflibercept (2 mg) once every 4 through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44. In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria.

Primary Outcome Measures

Name	Time	Method
Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in BRVO Participants.	Day 1 to Week 24	BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.
Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in All RVO Patients.	Day 1 to Week 24	BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants.	Baseline - Week 48	Macular Edema (ME) is assessed by optical coherence tomography (OCT) central subfield thickness (CST). A thickness of less than 325 microns is considered absence of ME. Proportion of participants with Absence of Macular Edema from Baseline to Week 48. Number of participants in each treatment arm who meet specified criteria at each visit from Week 1 through Week 48. Percentages are 100\*n/N.
Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants.	Day 1 - Week 48	Mean change in OCT center point retinal thickness (CPT) from baseline by visit over time (up to Week 48) for all RVO participants.
Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants.	Day 1 - Week 48	BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.
Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants.	Day 1 - Week 48	Number of participants in each treatment arm who meet specified criteria at each visit from Week 1 through Week 48. Percentages are 100\*n/N.
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants.	Baseline - Week 48	Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse from Baseline to Week 48. Snellen Equivalent of 20/200 is 38 ETDRS letters. Number of participants in each treatment arm who meet specified criteria at each visit from Baseline through Week 48. Percentages are 100\*n/N.
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants.	Day 1 - Week 48.	Percentage of participants with BCVA Snellen Equivalent of 20/40 or Better from Baseline to Week 48. Snellen Equivalent of 20/40 is 69 ETDRS letters. Number of participants in each treatment arm who meet specified criteria at each visit from Baseline through Week 48. Percentages are 100\*n/N.
Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants	Day 1 - Week 48	Number of participants in each treatment arm who meet specified criteria at each visit from Week 1 through Week 48. Percentages are 100\*n/N.
Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants.	Day 1 - Week 48	Mean change in OCT central subfield retinal thickness (CST) from baseline by visit over time (up to Week 48) for all RVO participants.

Trial Locations

Locations (140)

Northwest Arkansas Retina Associates; 🇺🇸 Phoenix, Arizona, United States

Retinal Research Institute, LLC; 🇺🇸 Phoenix, Arizona, United States

Retina Vitreous Associates; 🇺🇸 Beverly Hills, California, United States

Eye Medical Center of Fresno; 🇺🇸 Fresno, California, United States

Retina Consultants of Orange County; 🇺🇸 Fullerton, California, United States

UCSD Jacobs Retina Center; 🇺🇸 La Jolla, California, United States

Northern California Retina Vitreous Associates; 🇺🇸 Mountain View, California, United States

Retina Consultants of San Diego; 🇺🇸 Poway, California, United States

Retina Consultants of Southern California; 🇺🇸 Redlands, California, United States

Retinal Consultants Medical Group Inc; 🇺🇸 Sacramento, California, United States

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