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A Study to Evaluate the Efficacy and Safety of KSI-301, an Anti-VEGF Antibody Biopolymer Conjugate, Versus Aflibercept in Patients With Neovascular (Wet) Age-Related Macular Degeneration.

Phase 2
Terminated
Conditions
Wet Macular Degeneration
Interventions
Other: Sham Procedure
Registration Number
NCT04049266
Lead Sponsor
Kodiak Sciences Inc
Brief Summary

This study will evaluate the efficacy, safety, durability, and pharmacokinetics of KSI-301 administered at 12, 16 and 20 weeks intervals as specified in the protocol, compared with aflibercept once every 8 weeks (Q8W), in participants with treatment-naïve neovascular (wet) age-related macular degeneration (nAMD).

Detailed Description

This study is divided into a 3-week screening period, a 92-week treatment period, and a final 4-week follow-up period. At baseline patients will be randomized 1:1 into two treatment arms: KSI-301 5 mg and aflibercept 2 mg.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
559
Inclusion Criteria
  • Signed informed consent prior to participation in the study.
  • Active, treatment-naïve choroidal neovascularization (CNV) secondary to AMD.
  • BCVA ETDRS score between 80 and 25 letters (Snellen equivalent of 20/25 to 20/320), inclusive.
  • Other protocol-specified inclusion criteria may apply
Exclusion Criteria
  • CNV secondary to other causes in the Study Eye.
  • Any history of macular pathology unrelated to AMD but affecting vision or contributing to subretinal or intraretinal fluid.
  • Any history or evidence of a concurrent intraocular condition in the Study Eye that, in the judgment of the Investigator, could require either medical or surgical intervention during the study to prevent or treat visual loss.
  • Active ocular or periocular infection or inflammation.
  • Prior administration of any approved or investigational treatment for neovascular AMD in the Study Eye.
  • Uncontrolled glaucoma in the Study Eye.
  • Women who are pregnant or lactating or intending to become pregnant during the study.
  • Stroke or myocardial infarction in the 6-month period prior to Day 1.
  • Uncontrolled blood pressure defined as a systolic value > 180 mmHg or diastolic value ≥100 mmHg while at rest.
  • 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.
  • Other protocol-specified exclusion criteria may apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
KSI-301 5 mgSham ProcedureDrug: KSI-301 5 mg. KSI-301 5 mg will be administered by intravitreal injection into the study eye at 12, 16, and 20 weeks intervals as specified in the study protocol. Drug: Sham Procedure. The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Aflibercept 2 mgAfliberceptDrug: Aflibercept 2 mg. Aflibercept 2 mg will be administered by intravitreal injection into the study eye once every 4 weeks for 3 consecutive months, followed by once every 8 weeks. Drug: Sham Procedure. The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Aflibercept 2 mgSham ProcedureDrug: Aflibercept 2 mg. Aflibercept 2 mg will be administered by intravitreal injection into the study eye once every 4 weeks for 3 consecutive months, followed by once every 8 weeks. Drug: Sham Procedure. The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
KSI-301 5 mgKSI-301Drug: KSI-301 5 mg. KSI-301 5 mg will be administered by intravitreal injection into the study eye at 12, 16, and 20 weeks intervals as specified in the study protocol. Drug: Sham Procedure. The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 48 and 52, Full Analysis Set Year 1Year 1

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
NameTimeMethod
Percentage of Subjects on KSI-301 Arm With a Once Every 12-Weeks, 16-Weeks or 20-Weeks Treatment IntervalYear 1

Percentage of subjects on KSI-301 arm achieving a Once Every 12-Weeks, 16-Weeks or 20-Weeks Treatment Interval based on individualized treatment response

Percentage of Subjects Gaining ≥ 5, ≥10 and ≥15 Letters in BCVA From Baseline in the Study Eye, Full Analysis Set Year 1Year 1

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

Percentage of Subjects Who Achieving BCVA Snellen Equivalent of 20/40 or Better in the Study Eye at Year 1Year 1

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. BCVA Snellen equivalent of 20/40 was defined as ≥69 ETDRS letters

Percentage of Subjects With BCVA Snellen Equivalent of 20/200 or Worse in the Study Eye at Year 1Year 1

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. BCVA Snellen equivalent of 20/200 or Worse was defined as BCVA ≤ 38 ETDRS Letters.

Mean Change in OCT Central Subfield Retinal Thickness (CST) From Day 1Year 1

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.

Trial Locations

Locations (73)

Retinal Research Institute, LLC

🇺🇸

Phoenix, Arizona, United States

Northwest Arkansas Retina Associates

🇺🇸

Springdale, Arkansas, United States

California Retina Consultants

🇺🇸

Santa Maria, California, 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

Retina Associates of Orange County

🇺🇸

Laguna Hills, California, United States

Northern California Retina Vitreous Associates

🇺🇸

Mountain View, California, United States

Retina Consultants of San Diego

🇺🇸

Poway, California, United States

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

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