A Study to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Participants With Diabetic Macular Edema (DME)

Phase 3

Terminated

• Conditions: Diabetic Macular Edema
• Interventions: Drug: KSI-301; Drug: Aflibercept; Other: Sham Procedure

• Registration Number: NCT04603937
• 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 treatment-naïve DME.

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 treatment-naïve DME.

The primary endpoint will be assessed at Year 1; additional secondary endpoints for efficacy will be assessed at Years 1 and 2.

Study Timeline

• Study Start: 2020-09-30
• Study First Submitted: 2020-10-21
• Study First Submitted QC: 2020-10-26
• Study First Posted: 2020-10-27
• Primary Completion: 2023-04-27
• Study Completion: 2023-08-31
• Results First Submitted: 2024-07-25
• Status Verified: 2024-08
• Results First Submitted QC: 2024-08-20
• Last Update Submitted: 2024-08-20
• Results First Posted: 2024-08-22
• Last Update Posted: 2024-08-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 459

Inclusion Criteria

1. Signed informed consent prior to participation in the study.
2. Treatment-naïve diabetic macular edema, with vision loss and center involvement (if present) diagnosed within 9 months of screening.
3. BCVA ETDRS letter score between 78 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 DME.
6. Type 1 or Type 2 diabetes mellitus and a HbA1c of ≤12%.
7. Other protocol-specified inclusion criteria may apply.

Exclusion Criteria

1. Macular edema in the Study Eye considered to be secondary to a cause other than DME.
2. Active iris or angle neovascularization or neovascular glaucoma in the Study Eye.
3. High-risk proliferative diabetic retinopathy characteristics in the Study Eye.
4. History of Pan-retinal Photocoagulation (PRP) laser in the Study Eye within 3 months of screening.
5. Tractional retinal detachment in the Study Eye.
6. Active retinal disease other than the condition under investigation in the Study Eye.
7. Any history or evidence of a concurrent ocular condition present, 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 (e.g., vitreomacular traction, epiretinal membrane).
8. Active or suspected ocular or periocular infection or inflammation in either eye at Day 1.
9. Any prior use of an approved or investigational treatment for DME in the Study Eye (e.g., anti-VEGF, intraocular or periocular steroids, macular laser photocoagulation).
10. Women who are pregnant or lactating or intending to become pregnant during the study.
11. Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg or diastolic value ≥100 mmHg while at rest.
12. 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.
13. 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.
14. Other protocol-specified exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
KSI-301 (Arm A)	KSI-301	Intravitreal injection of KSI-301 (5 mg) once every 4 weeks for 3 monthly doses followed by an individualized dosing regimen (every 8 to 24 weeks) via intravitreal injection from Week 16 to Week 100.
KSI-301 (Arm A)	Sham Procedure	Intravitreal injection of KSI-301 (5 mg) once every 4 weeks for 3 monthly doses followed by an individualized dosing regimen (every 8 to 24 weeks) via intravitreal injection from Week 16 to Week 100.
Aflibercept (Arm B)	Sham Procedure	Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 5 monthly doses followed by aflibercept (2 mg) once every 8 weeks via intravitreal injection from Week 24 to 100.
Aflibercept (Arm B)	Aflibercept	Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 5 monthly doses followed by aflibercept (2 mg) once every 8 weeks via intravitreal injection from Week 24 to 100.

Primary Outcome Measures

Name	Time	Method
Mean Change in BCVA	Day 1 to Week 64	Mean change in best-corrected visual acuity (BCVA) from baseline to the average of Weeks 60 and 64 (using Early Treatment Diabetic Retinopathy Study (ETDRS) Letters). 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 Outcome Measures

Name	Time	Method
Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Studies KS301P104 and KS301P105 Combined	Day 1 to Week 52	Percentage of patients with a ≥ 2-step worsening on the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 52 using last observation carried forward (LOCF) in Studies KS301P104 and KS301P105 combined. The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached).
Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Study KS301P105	Day 1 to Week 52	Percentage of patients with a ≥ 2-step worsening on the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 52 using last observation carried forward (LOCF) in Study KS301P105. The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached).
Percentage of Patients in the KSI-301 Arm on a Q8W, Q12W, Q16W, Q20W, or Q24W Treatment Interval	Week 56	Percentage of patients in the KSI-301 arm on a Q8W, Q12W, Q16W, Q20W, or Q24W treatment interval at the primary endpoint. Analyses include KSI-301 patients who completed a treatment interval from Week 56 onwards.
Mean Number of Intravitreal Injections	Day 1 to Week 60	Mean number of intravitreal injections from Day 1 to Week 60
Mean Change in OCT CST	Day 1 to Week 64	Mean change in Optical Coherence Tomography (OCT) central subfield retinal thickness (CST) baseline to the average of Weeks 60 and 64

Trial Locations

Locations (71)

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

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

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

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

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

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

Retina Group of New England; 🇺🇸 Waterford, Connecticut, United States

Florida Eye Microsurgical Institute; 🇺🇸 Boynton Beach, Florida, United States

Rand Eye Institute; 🇺🇸 Deerfield Beach, Florida, United States

National Ophthalmic Research Institute; 🇺🇸 Fort Myers, Florida, United States

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